Magnetic field technology is a cutting-edge approach for the physical preservation of foods in recent years. The impact of short-term weak static magnetic field (SWMF) stimulation on the metabolite profiles and metabolic pathways of fresh-cut young ginger (FCYG) was investigated. Results showed that fresh-cut treatment (0 mT) caused large losses of volatile terpenes, increases in primary metabolite abundance, and alterations of secondary bioactive component composition in the FCYG. The 5 mT SWMF treatment better retarded these changes and its metabolite profiles were closest to the control sample. These results could be attributed to the inhibition of the respiration and energy-related pathways, i.e. glycolysis, TCA cycle, pentose phosphate pathway, carbon fixation in photosynthetic organisms, and purine metabolism in the FCYG. The suppression was linked to the significant reduction in the precursors and intermediates of key metabolic pathways. These findings could provide theoretical basis and technical reference for controlling FCYG quality.

Androgenetic alopecia (AGA) is the most common type of hair loss, with high incidence of comorbidities such as polycystic ovary syndrome (PCOS), metabolic syndrome, insulin resistance and cardiovascular diseases. Berberine (BBR) has been widely used clinically to treat diarrhea in China for a long time. Although recent studies have revealed its therapeutic potential in comorbidities of AGA, there are few reports on its regulatory effects on hair growth.

To explore the effects of BBR on hair loss and its mechanism.

Human dermal papilla cells (hDPCs), normal and miniaturized hair follicles (HFs) were employed to evaluate the impact of BBR on hair growth in vitro. Depilation-induced hair growth mouse model was used to find the optimum concentration of BBR in vivo. Network pharmacology, RNA sequencing, cell transfection and reporter gene assay, immunohistochemistry, and molecular docking verification were used to explore the molecular mechanisms.

These models revealed that BBR enhanced the proliferation of hDPCs, increased the length of both normal and miniaturized HFs, and prolonged the anagen phase. In the depilation-induced hair growth mouse model and histological staining, BBR treatment significantly accelerated hair growth, facilitated the transition to the anagen phase, and prolonged its duration. Mechanistic studies confirmed that BBR promoted hair growth through regulating cell cycle, mediated by targeting Axin and activating the Wnt/β-catenin pathway. Importantly, knockdown of Axin2 reduced BBR's ability to enhance hDPCs proliferation.

These results suggested that BBR promotes hair growth by targeting Axin2 and activating Wnt/β-catenin pathway, presenting a promising therapeutic avenue for hair loss treatment.

This study aimed to explore the molecular mechanism underlying the prognostic role of ancient ubiquitous protein 1 (AUP1) in head and neck squamous cell carcinoma (HNSCC) and its relationship with the tumor immune microenvironment. Various web resources were used to analyze the differential expression of AUP1 and its role in the HNSCC pathogenesis. A nomogram aimed at predicting 1-, 3-, and 5-year survival rates was developed based on the patient's clinicopathological characteristics and AUP1 expression pattern. Several algorithms and analytical tools were used to explore the correlation between AUP1 expression and sensitivity to immune checkpoint gene therapy by evaluating infiltrating immune cells in patients with HNSCC. Higher AUP1 mRNA and protein expression levels were observed in most tumors and HNSCC than in the normal tissues. High AUP1 expression was an independent predictive risk factor for the overall survival of patients as it was closely associated with the patients' T, M, clinical, and pathological stages and lymphovascular invasion in HNSCC. In conclusion, AUP1 is involved in the occurrence and progression of HNSCC, may be used as an independent prognostic factor in patients with HNSCC, and could serve as a potential intervention target to improve immunotherapy sensitivity in HNSCC.

Although Mendelian randomization (MR) studies on lung cancer (LC) have grown significantly, a comprehensive bibliometric analysis remains lacking. This study addresses that gap by examining global research trends, leading contributors, and emerging themes in MR related to LC.

We conducted a bibliometric analysis of publications from 2005 to 2024, using data from the Web of Science Core Collection. Research trends, collaboration networks, and key themes were visualized with VOSviewer, CiteSpace, and the R package 'bibliometrix'.

The analysis included 332 publications by 2,797 researchers across 50 countries. A notable increase in studies occurred after 2017, with China, the United States, and England as the top contributors. Key institutions included the University of Bristol and Nanjing Medical University. The most productive journals were Cancer Epidemiology, Biomarkers & Prevention and International Journal of Epidemiology, while Nature Genetics was the most cited. The research identified multiple causal pathways for LC linked to inflammation, genetics, lifestyle factors, lung diseases, and psychiatric conditions. Emerging themes include the roles of gut microbiota, schizophrenia, C-reactive protein, and asthma in LC development.

This bibliometric analysis of MR studies on LC highlights global research trends and emerging areas, particularly the roles of gut microbiota, schizophrenia, and inflammation in LC risk. These insights lay a strong foundation for advancing personalized prevention and treatment in future MR studies.

There is justification for optimism about the potential contribution of alternative medicines to cancer management, which now ranks as the second leading cause of death globally. Primary carcinogens arise from several sources, including agriculture, industry, and dietary intake. Gastric cancer (GC) significantly affects an individual's health due to its classification as a malignant tumor associated with elevated mortality and morbidity rates. Chemotherapy is now widely regarded as the gold standard for treating GC. Chemotherapy, however, exerts significant detrimental effects on human health, including irreversible damage to multiple organs. Consequently, it is essential to employ innovative strategies for cancer prevention. Natural products are now the focus of intensive study due to their efficacy against cancer and low toxicity levels. Natural compounds have shown a diverse range of anti-cancer properties. This review aims to emphasize studies on natural compounds that inhibit metastasis, induce apoptosis in GC, and decrease cellular proliferation. All the natural compounds from different sources were incorporated in this review not only medicinal plants derived compounds. This review aims to examine a comprehensive array of natural therapies that may enhance human health and facilitate GC prevention without inducing discernible negative effects. Moreover, this review aims to discuss the toxic side effects of phytochemicals and shed light on mechanisms underlying the action of potential natural products against GC. This review offers a novel perspective by integrating a broad spectrum of natural compounds from diverse sources, not limited to medicinal plants, to explore their anti-cancer properties against gastric cancer.

Cancer continues to be among the most substantial health challenges globally. Among various natural compounds, berberine, an isoquinoline alkaloid obtained from Coptidis Rhizoma, has garnered considerable attention for its broad-spectrum biological activities, including anti-inflammatory, antioxidant, anti-diabetic, anti-obesity, and anti-microbial activities. Furthermore, berberine exhibits a broad spectrum of anti-cancer efficacy against various malignancies, such as ovarian, breast, lung, gastric, hepatic, colorectal, cervical, and prostate cancers. Its anti-cancer mechanisms are multifaceted, encompassing the inhibition of cancer cell proliferation, the prevention of metastasis, the induction of apoptosis, the facilitation of autophagy, the modulation of the tumor microenvironment and gut microbiota, and the enhancement of the efficacy of conventional therapeutic strategies. This paper offers an exhaustive overview of the cancer-fighting characteristics of Coptidis Rhizoma and berberine, while also exploring recent developments in nanotechnology aimed at enhancing the bioavailability of berberine. Furthermore, the side effects and safety of berberine are addressed as well. The potential role of artificial intelligence in optimizing berberine's therapeutic applications is also highlighted. This paper provides precious perspectives on the prospective application of Coptidis Rhizoma and berberine in the prevention and management of cancer.

Glioblastoma (GBM) is one of the most invasive central nervous system tumors, with rising global incidence. Therapy resistance and poor prognosis highlight the urgent need for new anticancer drugs. Plant alkaloids, a largely unexplored yet promising class of compounds, have previously contributed to oncology treatments. While past reviews provided selective insights, this review aims to collectively compare data from the last decade on (1) plant alkaloid-based anticancer drugs, (2) alkaloid transport across the blood-brain barrier (BBB) in vitro and in vivo, (3) alkaloid mechanisms of action in glioblastoma models (in vitro, in vivo, ex vivo, and in silico), and (4) cytotoxicity and safety profiles. Additionally, innovative drug delivery systems (e.g., nanoparticles and liposomes) are discussed. Focusing on preclinical studies of single plant alkaloids, this review includes 22 botanical families and 28 alkaloids that demonstrated anti-GBM activity. Most alkaloids act in a concentration-dependent manner by (1) reducing glioma cell viability, (2) suppressing proliferation, (3) inhibiting migration and invasion, (4) inducing cell death, (5) downregulating Bcl-2 and key signaling pathways, (6) exhibiting antiangiogenic effects, (7) reducing tumor weight, and (8) improving survival rates. The toxic and adverse effect analysis suggests that alkaloids such as noscapine, lycorine, capsaicin, chelerythrine, caffeine, boldine, and colchicine show favorable therapeutic potential. However, tetrandrine, nitidine, harmine, harmaline, cyclopamine, cocaine, and brucine may pose greater risks than benefits. Piperine's toxicity and berberine's poor bioavailability suggest the need for novel drug formulations. Several alkaloids (kukoamine A, cyclovirobuxine D, α-solanine, oxymatrine, rutaecarpine, and evodiamine) require further pharmacological and toxicological evaluation. Overall, while plant alkaloids show promise in glioblastoma therapy, progress in assessing their BBB penetration remains limited. More comprehensive studies integrating glioma research and advanced drug delivery technologies are needed.

This review examines recent advancements in nanoparticle-based delivery systems for phytochemicals, focusing on their role in overcoming multidrug resistance, improving therapeutic efficacy, and facilitating clinical translation.

This review highlights recent advances in nanoparticle-enabled phytochemical delivery to enhance bioavailability, improve therapeutic outcomes, and enable targeted applications. By comparing various nanoparticle systems, formulation methods, and efficacy data, it identifies gaps in current research and guides the development of more effective, next-generation phytochemical-loaded nanocarriers.

A systematic review of literature published between 2000 and 2024 was conducted using PubMed, Scopus, and Web of Science. Articles focusing on nanoparticle-based phytochemical delivery in cancer therapy were included.

Compounds such as curcumin, resveratrol, quercetin, and epigallocatechin gallate demonstrate enhanced anti-cancer efficacy when encapsulated in nanoparticles, leading to improved bioavailability, increased tumor cell targeting, and reduced toxicity. Clinical trials indicate tumor regression and fewer adverse effects. Emerging approaches-such as nanogels, hybrid nanoparticles, and combination therapies with immune checkpoint inhibitors-further refine treatment efficacy.

Nanoparticle-based delivery systems significantly improve the therapeutic potential of phytochemicals, making them promising candidates for safer, more effective cancer treatments. However, challenges related to regulatory guidelines, scalability, and long-term safety must be addressed to fully realize their clinical potential.

Cancer is one of the major health problems worldwide and medicinal plants constitute a common alternative for cancer treatment having no or fewer side effects. This study aimed to assess total phenolic (TPC) and flavonoid (TFC) contents, antioxidant, biological activities (especially antibacterial, antifungal, and anticancer), and chemical composition of methanol extract of M. napaulensis DC. bark (MNBM). This is the first study evaluating its anticancer activity and chemical composition by LC-MS/MS analysis.

TPC, TFC, antioxidant, antimicrobial, and anticancer activities were determined by Folin-Ciocalteu, AlCl3, DPPH, Resazurin, and MTT assays, respectively. Its metabolite profiling was done by LC-MS/MS analysis. The statistical significance of differences between test groups was analyzed by a one-way ANOVA.

The preliminary phytochemical screening revealed the presence of various phytochemicals viz. alkaloids, steroids, glycosides, polyphenols, tannins, flavonoids, coumarins, terpenoids, and quinone. MNBM showed 38.00 ± 1.50 mg GAE g-1 dry sample as TPC, 35.04 ± 4.87 mg QE g-1 dry sample as TFC, and 212.97 μg/mL IC50 value (P < 0.05) as moderate antioxidant activity. MNBM showed minimal inhibitory concentration (MIC) values of 100.22 mg/mL, 50.15 mg/mL, and 25.08 mg/mL against S. aureus, E. coli, and C. albicans, respectively as weak antimicrobial activity. It showed no antibacterial effect against B. cereus and P. aeruginosa at 120 mg/mL. The anticancer activity of MNBM was moderate against human lung cancer cells A549 (228.97 μg/mL IC50 value) and human cervical cancer cells HeLa (367.72 µg/mL IC50 value) (P < 0.05). The LC-MS/MS analysis reported the presence of different anticancer compounds viz. dihydroberberine, d-berbamine, (S)-glaucine, protopine, grosheimin, mycophenolic acid, berberine, alpha-linolenic acid, etc. CONCLUSIONS: MNBM showed dose-dependent moderate antioxidant, weak antibacterial, weak antifungal, and moderate anticancer activity due to the synergistic effect of different phytochemicals and anticancer compounds.

Neurodegenerative diseases comprise a group of chronic, usually age-related, disorders characterized by progressive neuronal loss, deformation of neuronal structure, or loss of neuronal function, leading to a substantially reduced quality of life. They remain a significant focus of scientific and clinical interest due to their increasing medical and social importance. Most neurodegenerative diseases present intracellular protein aggregation or their extracellular deposition (plaques), such as α-synuclein in Parkinson's disease and amyloid beta (Aβ)/tau aggregates in Alzheimer's. Conventional treatments for neurodegenerative conditions incur high costs and are related to the development of several adverse effects. In addition, many patients are irresponsive to them. For these reasons, there is a growing tendency to find new therapeutic approaches to help patients. This review intends to investigate some phytocompounds' effects on neurodegenerative diseases. These conditions are generally related to increased oxidative stress and inflammation, so phytocompounds can help prevent or treat neurodegenerative diseases. To achieve our aim to provide a critical assessment of the current literature about phytochemicals targeting neurodegeneration, we reviewed reputable databases, including PubMed, EMBASE, and COCHRANE, seeking clinical trials that utilized phytochemicals against neurodegenerative conditions. A few clinical trials investigated the effects of phytocompounds in humans, and after screening, 13 clinical trials were ultimately included following PRISMA guidelines. These compounds include polyphenols (flavonoids such as luteolin and quercetin, phenolic acids such as rosmarinic acid, ferulic acid, and caffeic acid, and other polyphenols like resveratrol), alkaloids (such as berberine, huperzine A, and caffeine), and terpenoids (such as ginkgolides and limonene). The gathered evidence underscores that quercetin, caffeine, ginkgolides, and other phytochemicals are primarily anti-inflammatory, antioxidant, and neuroprotective, counteracting neuroinflammation, neuronal oxidation, and synaptic dysfunctions, which are crucial aspects of neurodegenerative disease intervention in various included conditions, such as Alzheimer's and other dementias, depression, and neuropsychiatric disorders. In summary, they show that the use of these compounds is related to significant improvements in cognition, memory, disinhibition, irritability/lability, aberrant behavior, hallucinations, and mood disorders.

Salvia miltiorrhiza, the anticancer properties of these components are multifaceted, encompassing the inhibition of tumor growth, prevention of the metastatic spread of cancer cells, enhancement of the sensitivity of cancer cells to chemotherapy and radiation therapy, and the suppression of angiogenesis, which is crucial for tumor growth and survival. In the context of our recent study, we have discovered that tanshinone I, one of the active components of Salvia miltiorrhiza, possesses the ability to inhibit the proliferation of ovarian cancer cells, both in laboratory settings and within living organisms. To further understand the molecular mechanisms behind this effect, we conducted a comprehensive transcriptomic analysis. Our findings indicated that tanshinone I exerts its inhibitory action by downregulating the expression of genes associated with glycolysis. Specifically, tanshinone I decreased the expression of glycolysis-related genes such as HK2 (hexokinase 2), PFK (phosphofructokinase), ENO2 (enolase 2), and LDHA (lactate dehydrogenase A). Inhibiting lactate production by tanshinone I application reduced the level of histone H3 lysine 18 lactylation (H3K18la), which reduced the expression of tumor-associated genes, such as TTK, PDGFRβ, YTHDF2 and RUBCNL. In addition, tanshinone I alleviated the immunosuppressive tumor microenvironment. In summary, tanshinone I blocks glycolysis to regulate histone H3 lysine 18 lactylation (H3K18la), which inhibits ovarian cancer cell growth, revealing the anticancer mechanism of tanshinone I.

The pharmaceutical industry and academia are continuously searching for novel and effective anticancer lead compounds to ensure patient safety, provide a cure, and surpass all other obstacles. Given the indeterminate nature of cancer etiology, the importance of drugs capable of targeting multiple pathways cannot be overstated. Among naturally occurring compounds, bisbenzylisoquinoline (BBIQ) alkaloids, such as berberine, tetrandrine, chelidonine, and berbamine, have demonstrated significant anticancer potential by modulating diverse signaling pathways. Several of these compounds are currently in clinical trials, highlighting their relevance in cancer treatment. This review emphasizes the need for further investigation into the anticancer properties of BBIQ alkaloids, particularly those isolated from eight Cyclea species in India. With around 27 BBIQ alkaloids identified, these compounds hold promise, especially in combating multidrug resistance-a critical challenge in cancer therapy. Given the rising cancer incidence, these alkaloids warrant a deeper exploration of their therapeutic potential.

Ulcerative colitis is a long-term inflammatory colon illness that significantly affects patients quality of life. Traditional medicines and therapies often come with challenges such as side effects, instability, unpredictability, and high costs. This has captured interest in natural products that have huge health benefits. Various natural compounds, including resveratrol, curcumin, quercetin, berberine, and hesperidin demonstrate immunomodulatory and oxido-inflammatory properties inside the gut epithelium, showing potential in managing ulcerative colitis. These compounds attenuate inflammatory mediators, NF-κB, and TLR4 signaling leading to a reduction in the production of inflammation-related cytokines, including TNF-α and IL-6. They also augment the activity of internal defense compounds, including superoxide radical dismutase enzyme and heme oxygenase-1, thereby alleviating oxidative damage. In addition, natural compounds have a profound effect on the endogenous microbiota and thus, support mucosal healing and intercellular barrier integrity. Both experimental and clinical analyses provide evidence that these bioactive compounds may help reduce clinical manifestations, induce and sustain remission, and improve the well-being of individuals suffering from ulcerative colitis. This review seeks to discuss various aspects of natural compounds in the management of ulcerative colitis, including mechanisms, therapeutic prospects, and hurdles, and hence the basis for future research and practice.

Breast cancer ranks as the second leading reason of cancer mortality among females globally, emphasizing the critical need for novel anticancer treatments. In current work, berberine-zinc oxide conjugated chitosan nanoparticles were synthesized and characterized using various characterization techniques. The cytotoxic effects of CS-ZnO-Ber NPs on MCF-7 cells were assessed using the MTT assay. Also, annexin V-FITC/PI double staining, Hoechst 33,342 staining, caspases-8 and 9 activity assays, and cell cycle analysis were performed. Furthermore, the mRNA levels of Bax and Bcl-2 genes were quantified using qPCR. Additionally, cell migration was evaluated using a scratch assay. The IC50 value of NPs against MCF-7 cells measured 7.41 µg/mL. Apoptosis induction in NP-treated cells was confirmed by Annexin V/PI staining, accompanied by the observation of condensed chromatin and fragmented DNA. Moreover, the pro-apoptotic potential of NPs was evidenced by significant increases in caspases-8 and 9 activity and a decreased Bcl-2/Bax ratio. Furthermore, cell cycle arrest at the sub-G1 was noticed in the treated cells. Additionally, the NPs markedly inhibited the migration rate of MCF-7 cells. These findings suggest that CS-ZnO-Ber NPs induce cell-cycle arrest and activate the apoptotic pathways in MCF-7 cells, highlighting their potential as a hopeful therapeutic agent for breast cancer.

Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies.

The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay.

E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 × 10-8 M (45.36 μg/ml) to 6.71 × 10-8 M (26.66 μg/ml) and Ifosfamide from 12.52 × 10-5 M (32.7 μg/ml) to 8.206 × 10-5 M (21.43 μg/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combination treatment. qRT-PCR analysis showed decreased expression of stemness-related genes CD44 and Nanog, and migration-related genes MMP2 and CXCL8 in the combination groups. Apoptosis-related genes Casp-3, Casp-9, and pP53 showed increased expression following combination therapy, while BAX expression increased and BCL2 expression decreased relative to the control.

The study demonstrates that combining E5-siRNA with Oxaliplatin or Ifosfamide enhances the efficacy of chemotherapy in HPV-16 positive cervical cancer cells. This synergistic approach effectively targets multiple aspects of cancer cell behavior, including proliferation, apoptosis, migration, and stemness. The findings suggest that this combination strategy could potentially allow for lower chemotherapy doses, thereby reducing toxicity while maintaining therapeutic efficacy. This research provides valuable insights into targeting HPV E5 as a complementary approach to existing therapies focused on E6 and E7 oncoproteins, opening new avenues for combination therapies in cervical cancer treatment.

Berberine (BBR) has been proved to inhibit the malignant progression of non-small cell lung cancer (NSCLC), but the underlying molecular mechanism still needs to be further revealed. NSCLC cells (A549 and H1299) were treated with BBR. CCK8 assay, colony formation assay, flow cytometry, TUNEL staining and transwell assay were used to examine cell proliferation, apoptosis and invasion. The levels of spindle pole body component 25 (SPC25) and NDC80 kinetochore complex component (NUF2) were detected by qRT-PCR or western blot. The interaction between SPC25 and NUF2 was confirmed by Co-IP assay and FISH assay. Xenograft tumors were constructed to assess the anti-tumor role of BBR in vivo. BBR inhibited NSCLC cell growth, invasion and glycolysis. SPC25 was upregulated in NSCLC tissues, and BBR could reduce SPC25 expression in NSCLC cells. SPC25 knockdown repressed NSCLC cell growth, invasion and glycolysis, and its overexpression also reversed the anti-tumor effect of BBR. SPC25 could interact with NUF2, and NUF2 overexpression abolished the inhibitory effect of SPC25 knockdown or BBR on NSCLC cell behaviors. In animal experiments, BBR could suppress NSCLC tumor growth by inhibiting SPC25/NUF2 axis in vivo. BBR mainly played an anti-NSCLC role by targeting SPC25/NUF2 axis, which provided a new idea for NSCLC treatment.

Argemone mexicana, commonly known as the Mexican prickly poppy, has been historically employed in traditional medicine for various ailments, including liver disorders. Given the rising prevalence of liver diseases, including cancer, investigating the potential efficacy of Argemone mexicana in promoting liver health is of paramount importance. This review aims to provide a comprehensive analysis of the existing literature on the hepatoprotective and anticancer properties of Argemone mexicana.

A systematic literature search was conducted across PubMed, Google Scholar, and relevant botanical and pharmacological databases. Studies from various sources, including in vitro experiments, animal models, and clinical trials, were included in the review. The search focused on articles published up to 2010-2023, encompassing research that explored the botanical characteristics, chemical composition, traditional uses, and pharmacological properties of Argemone mexicana, specifically emphasizing its impact on liver health and cancer.

The review revealed a wealth of studies highlighting the diverse pharmacological properties of Argemone mexicana. The botanical composition includes compounds with antioxidant and anti-inflammatory potential, suggesting hepatoprotective effects. Studies using in vitro and in vivo models demonstrated promising outcomes regarding liver function improvement and inhibition of liver cancer cell proliferation. While some clinical studies supported the traditional uses of Argemone mexicana, further well-designed trials are warranted to establish its clinical efficacy.

In conclusion, Argemone mexicana shows promise as a natural agent for promoting liver health and combating liver cancer. Bioactive compounds with antioxidant and anti-inflammatory properties suggest potential hepatoprotective effects. However, translating these findings into clinical practice requires further rigorous investigation, including well-designed clinical trials. This review provides a foundation for future research efforts aimed at elucidating the full therapeutic potential of Argemone mexicana in liver health and cancer management.

The fluorescence quantum yield of berberine in aqueous solution is significantly smaller than those of organic solution. The time profile of fluorescence intensity of berberine was analyzed by a bi-exponential function, showing that two kinds of states of berberine exist in the solutions. The observed fluorescence lifetime of shorter lifetime species of berberine in water (0.08 ns) was markedly smaller than those of organic solvents and the relative amplitude of the shorter lifetime was dominated in the aqueous solution. Thus, this shorter lifetime can be explained by the deactivation via intramolecular electron transfer. These two states of berberine were independent of pH. The enthalpy and entropy changes between these two states were - 23.2 kJ mol-1 and - 90 J K-1 mol-1, supporting the aggregation of berberine. In the aggregation state, an electrostatic interaction between cationic berberine and chloride ion decreases the electron accepting ability of the isoquinoline moiety of berberine, resulting in the suppression of intramolecular electron transfer. Furthermore, in the presence of clay, the interaction between berberine and clay increased the fluorescence intensity of berberine and its lifetime, showing that the negative charge of clay suppresses the intramolecular electron transfer. Since the electron transfer quenching of the photo-excited berberine is advantageous for suppressing the phototoxic effect of berberine, the inhibition of berberine aggregation is an important process for the phototoxicity prevention.

Gastric cancer (GC) is a common cancer worldwide. Therefore, searching for effective treatments is essential, and drug repositioning can be a promising strategy to find new potential drugs for GC therapy. For the first time, we sought to identify molecular alterations and validate new mechanisms related to Mebendazole (MBZ) treatment in GC cells through transcriptome analysis using microarray technology. Data revealed 1066 differentially expressed genes (DEGs), of which 345 (2.41 %) genes were upregulated, 721 (5.04 %) genes were downregulated, and 13,231 (92.54 %) genes remained unaltered after MBZ exposure. The overexpressed genes identified were CCL2, IL1A, and CDKN1A. In contrast, the H3C7, H3C11, and H1-5 were the top 3 underexpressed genes. Gene set enrichment analysis (GSEA) identified 8 pathways significantly overexpressed in the treated group (p < 0.05 and FDR<0.25). The validation of the expression of top desregulated genes by RT-qPCR confirmed the transcriptome results, where MBZ increased the CCL2, IL1A, and CDKN1A and reduced the H3C7, H3C11, and H1-5 transcript levels. Expression analysis in samples from TCGA databases correlated that the lower ILI1A and higher H3C11 and H1-5 gene expression are associated with decreased overall survival rates in patients with GC, indicating that MBZ treatment can improve the prognosis of patients. Thus, the data demonstrated that the drug MBZ alters the transcriptome of the AGP-01 lineage, mainly modulating the expression of histone proteins and inflammatory cytokines, indicating a possible epigenetic and immunological effect on tumor cells, these findings highlight new mechanisms of action related to MBZ treatment. Additional studies are still needed to better clarify the epigenetic and immune mechanism of MBZ in the therapy of GC.

Berberine (BBR) is an isoquinoline alkaloid extracted from Huang Lian and other herbal medicines. It has been reported to play a crucial role in multiple metabolic diseases and cancers. Programmed cell death-1 (PD-L1) is known as the immune checkpoint; immunotherapy targeting PD1/PD-L1 axis can effectively block its pro-tumor activity. However, the effect of the combined use of BBR and anti-PD-L1 on hepatocellular carcinoma (HCC) has not been reported.

Hep-3B and HCCLM3 cells were chosen as the experimental objects. To determine the potential anti-cancer activity of the combination of BBR and anti-PD-L1, we first treated v cells with BBR. The cell viability of Hep-3B and HCCLM3 with BBR treatment was measured by Cell Count Kit 8 assay. Cytometry by time-of-flight was performed to analyze tumor tissues after treatment with BBR and/or anti-PD-L1. Proliferation-, migration-, and invasion-related markers were measured by western blotting and immunohistochemistry.

The results showed that BBR significantly inhibited the proliferation of Hep-3B and HCCLM3.The combination treatment of BBR and anti-PD-L1 had a prominent inhibitory effect on HCC tumorigenesis. Cytometry by time-of-flight analysis indicated that BBR affects the immune subsets in the tumors. Besides, BBR and anti-PD-L1 inhibited the migration and invasion of HCC by inactivating the phosphorylation of Erk.

Our study proposed that the combination treatment of BBR and anti-PD-L1 markedly inhibited the tumorigenesis of HCC by Erk signaling pathway. We hope our research can provide a new strategy for the potential of BBR as a therapeutic agent in the treatment of HCC.

Despite the advancement in cancer diagnosis and treatment, colorectal cancer remains the leading cause of cancer-related death worldwide. Given the high recurrence rate of colorectal cancer even after surgical resection, chemotherapy has been clinically used to improve the treatment outcomes of colorectal cancer. However, chemotherapy is well-known for its toxic side effects. Thus, phytochemicals have been widely studied in recent years as preventive and therapeutic agents for colorectal cancer owing to their relatively low toxicity. Moreover, combinatorial uses of phytochemicals with other natural compounds or with drugs may amplify the positive outcomes of colorectal cancer prevention and treatment by intervening in multiple signaling pathways and targets. This review summarized the combinatorial use of several well-studied groups of phytochemicals, that is, isothiocyanates, quinones, carotenoids, and alkaloids, in the prevention and treatment of colorectal cancer, and suggested it as a potential approach to improve the anticancer efficacy of single compounds and minimize the toxic side effects associated with conventional drugs. Notably, we generalized the in vitro, in vivo, and clinical experiments-based molecular mechanisms whereby the selected phytochemicals in combination with other compounds exerted anti-colorectal cancer effects by inhibiting cancer cell proliferation, cell apoptosis, cell invasion, and tumor growth. Overall, this review provides a reference and new perspective to propel further advancements in research and development of preventative and therapeutic strategies for colorectal cancer.

Hepatocellular carcinoma (HCC) exhibits a propensity for early recurrence following liver resection, resulting in a bleak prognosis. At present, majority of the predictive models for the early postoperative recurrence of HCC rely on the linear assumption of the Cox Proportional Hazard (CPH) model. However, the predictive efficacy of this model is constrained by the intricate nature of clinical data. The present study aims to investigate the efficacy of the random survival forest (RSF) model, which is a machine learning algorithm, in predicting the early postoperative recurrence of HCC, and compare its performance with that of the traditional CPH model. This analysis seeks to elucidate the potential advantages of the RSF model over the CPH model in addressing this clinical challenge.

The present retrospective cohort study was conducted at a single center. After excluding 41 patients, a total of 541 patients were included in the final model construction and subsequent analysis. The patients were randomly divided into two groups at a 7:3 ratio: training group (n = 378) and validation group (n = 163). The least absolute shrinkage and selection operator (LASSO) regression was used to identify the risk factors in the training group. Then, the identified factors were used to develop the RSF and CPH regression models. The predictive ability of the model was assessed using the concordance index (C-index). The accuracy of the model predictions was evaluated using the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic curve (AUC). The clinical practicality of the model was measured by decision curve analysis (DCA), and the overall performance of the model was evaluated using the Brier score. The RSF model was visually represented using the Shapley additive explanations (SHAP) framework. Then, the RSF, CPH regression, and albumin-bilirubin (ALBI) grade models were compared.

The following variables were examined by LASSO regression: alpha fetoprotein (AFP), gamma-glutamyl transpeptidase to platelet ratio (GPR), blood transfusion (BT), microvascular invasion (MVI), large vessel invasion (LVI), Edmondson-Steiner (ES) grade, liver capsule invasion (LCI), satellite nodule (SN), and Barcelona clinic liver cancer (BCLC) grade. Then, a RSF model was developed using 500 trees, and the variable importance (VIMP) ranking was MVI, LCI, SN, BT, BCLC, ESG, AFP, GPR and LVI. After these aforementioned factors were applied, the RSF and CPH regression models were developed and compared using the ALBI grade model. The C-index for the RSF model (0.896 and 0.798, respectively) outperformed that of the CPH regression model (0.803 and 0.772, respectively) and ALBI grade model (0.517 and 0.515, respectively), in both the training and validation groups. Three time points were selected to assess the predictive capabilities of these models: 6, 12 and 18 months. For the training group, the AUC value for the RSF model at 6, 12 and 18 months was 0.971 (95% CI: 0.955-0.988), 0.919 (95% CI: 0.887-0.951) and 0.899 (95% CI: 0.867-0.932), respectively. For the validation cohort, the AUC value for the RSF model at 6, 12 and 18 months was 0.830 (95% CI: 0.728-0.932), 0.856 (95% CI: 0.787-0.924) and 0.832 (95% CI: 0.764-0.901), respectively. The AUC values were higher in the RSF model, when compared to the CPH regression model and ALBI grade model, in both groups. The DCA results revealed that the net clinical benefits associated to the RSF model were superior to those associated to the CPH regression model and ALBI grade model in both groups, suggesting a higher level of clinical utility in the RSF model. The Brier score for the RSF model at 6, 12 and 18 months was 0.062, 0.125 and 0.178, respectively, in the training group, and 0.111, 0.128 and 0.149, respectively, in the validation group. In summary, the RSF model demonstrated superior performance, when compared to the CPH regression model and ALBI grade model. Furthermore, the RSF model demonstrated superior predictive ability, accuracy, clinical practicality, and overall performance, when compared to the CPH regression model and ALBI grade model. In addition, the RSF model was able to successfully stratify patients into three distinct risk groups (low-risk, medium-risk and high-risk) in both groups (p < 0.001).

The RSF model demonstrates efficacy in predicting early recurrence following HCC surgery, exhibiting superior performance, when compared to the CPH regression model and ALBI grade model. For patients undergoing HCC surgery, the RSF model can serve as a valuable tool for clinicians to postoperatively stratify patients into distinct risk categories, offering guidance for subsequent follow-up care.

Visceral pleural infiltration (VPI) has been identified as an important risk factor in nonsmall cell lung cancer (NSCLC) for many decades. However, for patients who present with ground glass opacity (GGO), the prognostic value of VPI is still elusive. The authors aimed to investigate whether the VPI is a significant prognostic factor in surgically resected ≤3 cm stage I NSCLC, who presented with GGO.

Patients with primary NSCLC who underwent surgical resection between December 2009 and December 2018 were collected. Stage I tumors that presented as GGO nodules with a tumor size of less than 3 cm were included and divided into two groups based on VPI status (positive and negative). Clinical, pathological, and prognostic data were prospectively collected and retrospectively reviewed. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using the Cox proportional hazards model and Kaplan-Meier method.

A total of 2043 patients were included in this study (VPIs were found in 196 patients). After IPTW weighting, all factors between the two groups were balanced. The median follow-up time was 67.3 months. According to the multivariable Cox models, the VPI was not a significant prognostic factor for OS (HR=2.00, 95% CI: 0.96-4.17; P =0.063), but was significant for RFS (HR=2.00, 95% CI: 1.12-3.55; P =0.019). In subgroup analysis, we found VPI was significant for OS (HR=3.17, 95% CI: 1.09-9.26, P =0.035) and RFS (HR=4.07, 95% CI: 1.76-9.40, P =0.001) in patients with a tumor size >1 cm and a consolidation to tumor ratio (CTR) >50%. For patients with a tumor size ≤1 cm or a CTR ≤50%, the VPI was not significant.

VPI may be a significant risk factor for GGOs in NSCLC patients with a tumor size >1 cm and a CTR >50%. Further prospective studies conducted across multicenters with a larger sample size are needed.

Triple negative breast cancer is considered to be a malignancy of grave concern with limited routes of treatment due to the absence of specific breast cancer markers and ambiguity of other potential drug targets. Poor prognosis and inadequate survival rates have prompted further research into the understanding of the molecular pathophysiology and targeting of the disease. To overcome the recurrence and resistance mechanisms of the TNBC cells, various approaches have been devised, and are being continuously evaluated to enhance their efficacy and safety. Chemo-Adjuvant therapy is one such treatment modality being employed to improve the efficiency of standard chemotherapy. Combining chemo-adjuvant therapy with other upcoming approaches of cancer therapeutics such as phytoconstituents and nanotechnology has yielded promising results in the direction of improving the prognosis of TNBC. Numerous nanoformulations have been proven to substantially enhance the specificity and cellular uptake of drugs by cancer cells, thus reducing the possibility of unintended systemic side effects within cancer patients. While phytoconstituents offer a wide variety of beneficial active constituents useful in cancer therapeutics, most favorable outcomes have been observed within the scope of polyphenols, isoquinoline alkaloids and isothiocyanates. With an enhanced understanding of the molecular mechanisms of TNBC and the advent of newer targeting technologies and novel phytochemicals of medicinal importance, a new era of cancer theranostic treatments can be explored. This review hopes to instantiate the current body of research regarding the role of certain phytoconstituents and their potential nanoformulations in targeting specific TNBC pathways for treatment and diagnostic purposes.

Soy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer.

A two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk.

A nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57-0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008).

We identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.

Previous reports from our laboratory describing the formation of myofibrils in cultured embryonic cardiac and skeletal muscle cells have proposed that myofibrillogenesis occurs in three steps of increasing protein organization: beginning with premyofibrils, followed by nascent myofibrils, and ending in mature myofibrils. Inhibitors of the ubiquitin proteasome system (UPS) prevented nascent myofibrils from progressing directly to mature myofibrils in cultured cardiac and skeletal muscle cells, supporting a three-step model of assembly in which some of the proteins in nascent myofibrils are proteolyzed to allow the assembly of mature myofibrils. Application of UPS inhibitors on cultured muscle cells suggests possible explanations for the off-target cardiac and skeletal muscle adverse effects of UPS drugs, which are used on cancer patients. Berberine, a plant derivative, has been used to treat various cancers, including multiple myelomas. In contrast to the use of UPS drugs, success was reported with Berberine in multiple myeloma patients with no off-target effects on their hearts. We have exposed cultured cardiac and skeletal muscle cells to Berberine, a ligase inhibitor of UHRF1 (ubiquitin-like with PHD and RING finger domains). Berberine inhibited myofibril assembly at the nascent myofibril stage in embryonic skeletal muscle cells but had no effect in the assembly of mature myofibrils in embryonic heart cells. RT-PCR experiments demonstrated Berberine inhibition of mRNA for muscle myosin II heavy chains but not for muscle actin mRNA in skeletal muscle cells. Berberine is also being used as a popular weight losing compound, because it is much cheaper and available without a prescription than the semaglutide containing weight losing drugs (Wegovy and Ozempic). In contrast to Berberine, semaglutide had no effects on myofibril assembly in culture assays for both cardiac and skeletal muscle cells. We postulate that analyses of cultured embryonic cardiac and skeletal muscle cells will provide a preclinical assay for the testing of novel cancer drugs with improved outcomes for patients, an important goal for cancer therapeutics.

Meningeal metastasis (LM) is commonly seen in the advanced stages of cancer patients, often leading to a rapid decline in survival time and quality of life. Currently, there is still a lack of standardized treatments. Oncolytic viruses (OVs) are a class of emerging cancer therapeutics with the advantages of selectively replicating in cancer cells, delivering various eukaryotic transgenes, inducing immunogenic cell death, and promoting anti-tumor immunity. Some studies applying OVs intrathoracically or intraperitoneally for the treatment of malignant pleural and peritoneal effusions have shown promising therapeutic effects. If OVs could be applied to treat LM, it would bring significant survival benefits to patients with LM. In this review, we analyzed past research on the use of viruses to treat meningeal metastasis, summarized the efficacy and safety demonstrated by the research results, and analyzed the feasibility of oncolytic virus therapy for meningeal metastasis. We also summarized the existing data to provide guidance for the development of OVs that can be injected into the cerebrospinal fluid (CSF).

Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells.

LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 μM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling.

The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment.

Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.

Understanding the role of TRIB3 in cellular chemotherapy responsiveness and survival could facilitate its development as a prognostic marker that could be used to improve chemotherapeutic efficiency against specific tumors. Therefore, the role of TRIB3 to reflect the cytotoxic abilities of chemotherapeutic agents was clarified in the tested gastric cancer cell lines.

We have comprehensively investigated the protein expression of TRIB3 in three gastric cancer cell lines AGS, TMK-1, and MKN-45 cells treated with the anticancer drugs, 5-fluorouracil, cisplatin, and docetaxel. The Cell Count kit-8 was used to evaluate cell viability. Immunoblotting was performed to assay protein levels after drug treatment. Flow cytometry was carried out to evaluate the levels of sub-G1 cell population.

Treatment of the tested gastric cancer cell lines dose-dependently decreased cell viability and protein levels of TRIB3 while increasing apoptosis. Overexpression of TRIB3 protects MKN-45 cells from endoplasmic reticulum stress-induced apoptosis but does not influence the induction of autophagy by anticancer drugs. In addition, overexpression of TRIB3 also rescued paroxetine-induced apoptosis and endoplasmic reticulum stress.

Our previous and present results indicate that TRIB3 can protect gastric cancer cells against anticancer drug treatment and that downregulating TRIB3 may increase these cells' sensitivity to anticancer drugs. We thus suggest that the capability of anticancer drugs to downregulate TRIB3 can indicate tumors' potential susceptibility to these drugs.

Cancer is one of the most common causes of death in the world. Despite the fact that there are many types of therapies available, cancer treatment remains a major challenge. The main reason for the ineffectiveness of chemotherapy is the acquisition of multidrug resistance (MDR) by cancer cells. One of the factors responsible for the acquisition of MDR is the NRF2 transcription factor, which regulates the expression of proteins such as HO-1, NQO1, MRP1, MRP2, and GST. In normal cells, NRF2 is the first line of defense against oxidative stress, thereby preventing carcinogenesis. Still, its hyperactivation in cancer cells causes them to acquire MDR, which significantly reduces or eliminates the effectiveness of chemotherapy. Considering the important role NRF2 plays in the acquisition of MDR, its modulators and, above all, inhibitors are being sought after, including among compounds of plant origin. NRF2 inhibition may prove to be a key element of anticancer therapy. This review summarizes the current state of knowledge about plant NRF2 inhibitors and presents the effects of their use in overcoming MDR in cancer.

Microbial combating is one of the hot research topics, and finding an alternative strategy is considerably required nowadays. Here, we report on a developed combined chemo- and photodynamic delivery system with a core of zinc oxide nanoparticles (ZnO NPs), porphyrin photosensitizer (POR) connected to alginate polymer (ALG), and berberine (alkaloid natural agent, BER) with favorable antimicrobial effects. According to the achieved main designs, the results demonstrated that the loading capacity and entrapment efficiency reached 22.2 wt % and 95.2%, respectively, for ZnO@ALG-POR/BER nanoformulation (second design) compared to 5.88 wt % and 45.1% for ZnOBER@ALG-POR design (first design). Importantly, when the intended nanoformulations were combined with laser irradiation for 10 min, they showed effective antifungal and antibacterial action against Candida albicans, Escherichia coli, and Staphylococcus aureus. Comparing these treatments to ZnO NPs and free BER, a complete (100%) suppression of bacterial and fungal growth was observed by ZnO@ALG-POR/BER nanoformulation treated E. coli, and by ZnOBER treated C. albicans. Also, after laser treatments, most data showed that E. coli was more sensitive to treatments using nanoformulations than S. aureus. The nanoformulations like ZnOBER@ALG-POR were highly comparable to traditional antibiotics against C. albicans and E. coli before laser application. The results of the cytotoxicity assessment demonstrated that the nanoformulations exhibited moderate biocompatibility on normal human immortalized retinal epithelial (RPE1) cells. Notably, the most biocompatible nanoformulation was ZnOBER@ALG-POR, which possessed ∼9% inhibition of RPE1 cells compared to others. High binding affinities were found between all three microbial strains' receptor proteins and ligands in the molecular docking interaction between the receptor proteins and the ligand molecules (mostly BER and POR). In conclusion, our findings point to the possible use of hybrid nanoplatform delivery systems that combine natural agents and photodynamic therapy into a single therapeutic agent, effectively combating microbial infections. Therapeutic efficiency correlates with nanoformulation design and microorganisms, demonstrating possible optimization for further development.

Heterogeneity of hepatocellular carcinoma (HCC) presents significant challenges for therapeutic strategies and necessitates combinatorial treatment approaches to counteract suppressive behavior of tumor microenvironment and achieve improved outcomes. Here, we employed cytokines to induce memory-like behavior in natural killer (NK) cells, thereby enhancing their cytotoxicity against HCC. Additionally, we evaluated the potential benefits of combining sorafenib with this newly developed memory-like NK cell (pNK) immunochemotherapy in a preclinical model.

HCC tumors were grown in SD rats using subcapsular implantation. Interleukin 12/18 cytokines were supplemented to NK cells to enhance cytotoxicity through memory activation. Tumors were diagnosed using MRI, and animals were randomly assigned to control, pNK immunotherapy, sorafenib chemotherapy, or combination therapy groups. NK cells were delivered locally via the gastrointestinal tract, while sorafenib was administered systemically. Therapeutic responses were monitored with weekly multi-parametric MRI scans over three weeks. Afterward, tumor tissues were harvested for histopathological analysis. Structural and functional changes in tumors were evaluated by analyzing MRI and histopathology data using ANOVA and pairwise T-test analyses.

The tumors were allowed to grow for six days post-cell implantation before treatment commenced. At baseline, tumor diameter averaged 5.27 mm without significant difference between groups (p = 0.16). Both sorafenib and combination therapy imposed greater burden on tumor dimensions compared to immunotherapy alone in the first week. By the second week of treatment, combination therapy had markedly expanded its therapeutic efficacy, resulting in the most significant tumor regression observed (6.05 ± 1.99 vs. 13.99 ± 8.01 mm). Histological analysis demonstrated significantly improved cell destruction in the tumor microenvironment associated with combination treatment (63.79%). Interestingly, we observed fewer viable tumor regions in the sorafenib group (38.9%) compared to the immunotherapy group (45.6%). Notably, there was a significantly higher presence of NK cells in the tumor microenvironment with combination therapy (34.79%) compared to other groups (ranging from 2.21 to 26.50%). Although the tumor sizes in the monotherapy groups were similar, histological analysis revealed a stronger response in pNK cell immunotherapy group compared to the sorafenib group.

Experimental results indicated that combination therapy significantly enhanced treatment response, resulting in substantial tumor growth reduction in alignment with histological analysis.

Oxidative stress is a key factor in the development of chronic diseases such as type 2 diabetes, cardiovascular diseases, and liver disorders. Antioxidant therapies that target oxidative damage show significant promise in preventing and treating these conditions. Berberine, an alkaloid derived from various plants in the Berberidaceae family, enhances cellular defenses against oxidative stress through several mechanisms. It activates the AMP-activated protein kinase (AMPK) pathway, which reduces mitochondrial reactive oxygen species (ROS) production and improves energy metabolism. Furthermore, it boosts the activity of key antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), thus protecting cells from oxidative damage. These actions make berberine effective in managing diseases like type 2 diabetes, cardiovascular conditions, and neurodegenerative disorders. Silymarin, a flavonolignan complex derived from Silybum marianum, is particularly effective for liver protection. It activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, enhancing antioxidant enzyme expression and stabilizing mitochondrial membranes. Additionally, silymarin reduces the formation of ROS by chelating metal ions, and it also diminishes inflammation. This makes it beneficial for conditions like non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disorders. This review aims to highlight the distinct mechanisms by which berberine and silymarin exert their antioxidant effects.

Despite various treatment modalities, the progression and metastasis of breast cancer (BC) are grave concerns due to the alarming disease-free survival rate (DFS) and overall survival rate (OS) of affected patients. Over the years, many antibiotics, synthetic compounds, medicinal plant isolates and polyherbal combinations have been used as adjuvants in therapy for the management of primary and secondary tumors. Paclitaxel (PTX)-based chemotherapy for breast cancer causes multiple adverse side effects in patients. Withania somnifera (L.) Dunal (WS) and Asparagus racemosus Willd. (AR) as Ayurveda-inspired plant-based adjuvants were investigated for their anticancer effects on MDA-MB-231 and 4T1 cells in mouse model systems.

This study focused on evaluating the adjuvant properties of WS and AR plant extracts with PTX and their effectiveness over PTX alone in terms of tumor inhibition.

The effects of WS and AR on DNA double-strand breaks (DSBs), senescence induction and mitochondrial functions were evaluated in BC cells in vitro. The potential for cancer stem cell (CSC) inhibition was evaluated via mammosphere formation assays and CD44/CD24 immunostaining. In vivo tumor growth studies were conducted in athymic BALB/c mice for MDA-MB-231 cells and in BALB/c mice for 4T1 cells.

Induction of senescence was evident due to DSBs induced by the WS and AR extracts. Mammosphere formation and CD44/CD24 CSC markers were reduced after treatment with WS, AR or the combination of both in MCF-7 cells. WS or AR inhibited epithelial-to-mesenchymal transition (EMT). In vivo studies demonstrated that tumor growth inhibition was more pronounced in the treated group than in the PTX alone group and the untreated control group.

Our study showed that the use of WS or AR plant hydroalcoholic extracts in combination with paclitaxel (PTX) has better effects on sensitivity and efficacy than PTX alone, as demonstrated in in vitro BC cells and mouse models with BC cell grafts. Hence, scheduling adjuvant therapy with WS or AR alone or combined with PTX can be advantageous for the management of triple-negative BC (TNBC). Further studies are warranted in human clinical conditions to ascertain the efficacy of these treatments.

Berberine (BBR) is a natural alkaloid, which has played an important role in the field of medicine since its discovery in the late 19th century. However, the low availability of BBR in vivo prevents its full effect. In recent years, a large number of studies confirmed that BBR has a protective effect on the nervous system through various functions, yet the issue of the inability to systematically understand the protection of BBR on the nervous system remains a gap that needs to be addressed. Many existing literature introductions about berberine in neurodegenerative diseases, but the role of berberine in the nervous system goes far beyond these. Different from these literatures, this review is divided into three parts: preparation method, mechanism, and therapeutic effect. Various dosage forms of BBR and their preparation methods are added, in order to provide a reasonable choice of BBR, and help to solve the problem of low bioavailability in treatment. More importantly, we more comprehensively summarize the mechanism of BBR to protect the nervous system, in addition to the treatment of neurodegenerative diseases (anti-oxidative stress, anti-neuroinflammation, regulation of apoptosis), two extra mechanisms of berberine for the protection of the nervous system were also introduced: bidirectional regulation of autophagy and promote angiogenesis. Also, we have clarified the precise mechanism by which BBR has a therapeutic effect not only on neurodegenerative illnesses but also on multiple sclerosis, gliomas, epilepsy, and other neurological conditions. To sum up, we hope that these can evoke more efforts to comprehensively utilize of BBR nervous system, and to promote the application of BBR in nervous system protection.

Berberine (BER) is an alkaloid found, together with other protoberberinoids (PROTBERs), in several species used in medicines and food supplements. While some herbal preparations containing BER and PROTBERs, such as Berberis aristata DC. bark extracts, have shown promising potential for human health, their safety has not been fully assessed. Recently, the EFSA issued a call for data to deepen the pharmacokinetic and pharmacodynamic understanding of products containing BER and PROTBERs and to comprehensively assess their safety, especially when used in food supplements. In this context, new data were collected in this work by assessing: (i) the phytochemical profile of 16 different commercial B. aristata dry extracts, which are among the most widely used preparations containing BER and PROTBERs in Europe; (ii) the In Vitro and In Silico investigation of the pharmacokinetic properties of BER and PROTBERs; (iii) the In Vitro cytotoxicity of selected extracts in different human cell lines, including tests on hepatic cells in the presence of CYP450 substrates; (iv) the effects of the extracts on cancer cell migration; and (v) the In Vitro molecular effects of extracts in non-cancer human cells. Results showed that commercial B. aristata extracts contain BER as the main constituent, with jatrorrhizine as main secondary PROTBER. BER and jatrorrhizine were found to have a good bioaccessibility rate, but they interact with P-gp. B. aristata extracts showed limited cytotoxicity and minimal interaction with CYP450 substrates. Furthermore, tested extracts demonstrated inhibition of cancer cell migration and were devoid of any pro-tumoral effects in normal cells. Overall, our work provides a valuable overview to better elucidate important concerns regarding botanicals containing BER and PROTBERs.

Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are critical components of the extracellular matrix (ECM) in colorectal cancer (CRC). We aimed to evaluate the prognostic value of MMP-2 and MMP-9 in patients with CRC.

We performed a meta-analysis of cohort studies with available data on the effect of MMP-2 and MMP-9 expression on both disease-free survival (DFS) and overall survival (OS) by the risk ratios (RRs) with their 95% confidence intervals (CIs). Studies were subgrouped based on the different tissue types, including cancer tissue and normal tissue, and the subgroup effect of MMP expression in different tissues was analyzed through meta-regression. To ensure the quality and reduce the risk of bias, the Newcastle‒Ottawa Scale (NOS) was used to assess the included studies. A sensitivity analysis was randomly performed to assess the potential impact of each study on our results.

Eighteen trials were selected (Table 1) and included a total of 3944 patients. According to our primary meta-analysis, the expression of MMP-2 was significantly associated with a decrease in OS (RR = 1.75, 95% CI = 1.34 to 2.29, P < 0.001) and DFS (RR = 2.62, 95% CI = 1.25 to 5.49, P < 0.001), and the expression of MMP-9 was not significantly associated with a decrease in OS (RR = 1.48, 95% CI = 0.97 to 2.24, P = 0.069) or DFS (RR = 1.60, 95% CI = 0.87 to 2.94, P = 0.133). According to the subgroup analysis of MMPs in different tissues, high MMP-2 expression in cancer tissue (RR = 1.90, 95% CI = 1.29 to 2.79) and normal tissue (RR = 1.59, 95% CI = 1.17 to 2.17) were significant indicators of poor OS. High MMP-2 expression in cancer tissue was significant indicator of poor DFS (RR = 2.12, 95% CI = 1.09 to 4.11). MMP-9 expression was also associated with poor OS (RR = 1.40, 95% CI = 0.85 to 2.29), but the difference in OS between the high and low expression groups was not statistically significant.

High MMP-2 expression, especially in cancer tissue, is significantly associated with both poor DFS and poor OS in patients with CRC. High MMP-9 expression tended to indicate a poor prognosis of CRC but the correlation was not significant.

To investigate the effects of berberine (BBR) as a treatment on intestinal microecological alterations and enteritis in mice produced by TNBS.

There were seven mice per group: seven in the healthy group (Ctrl), seven in the TNBS-induced enteritis group (TNBS), and seven in the berberine treatment group (BBR). The mice were weighed, slaughtered after 7 days, and subjected to high-throughput intestinal microecological analysis by Illumina, as well as haematological detection and imaging evaluation of colon pathology.

The alterations in colon length, immune cell subpopulations, inflammatory factors, and intestinal microecology of mice induced by BBR were refined using a battery of experiments and observations. According to intestinal microecological studies, BBR can increase the number of bacteria, including Lactobacillus, Verrucomicrobia, Bacteroides, and Akkermansia muciniphila.

BBR has a therapeutic effect on TNBS-induced colitis in mice, which is associated with modifications in immune cell subpopulations and intestinal microecology. It also offers a viable approach as a prospective probiotic (like Akkermansia muciniphila) to IBD therapy in clinical settings.

Multiple compounds are related to the development of liver injury, such as toxins, drugs, and environmental pollutants. Although there are reports that the T-2 toxin can cause liver injury, its toxic mechanism remains unclear, which further impedes the development of effective antidotes. In this study, CRISPR-Cas9 genome-wide screening technology was used to identify transformation-related protein 53 inducible nuclear protein 1 (trp53inp1) as a toxic target of the T-2 toxin. Mechanism studies have shown that the T-2 toxin induced pyroptosis of macrophages (J774A.1 cells) by activating the trp53inp1/NF-κB/NLRP3/GSDMD-N pathway, leading to a subacute liver injury. Also, the new drug berberine (BER) identified through virtual screening significantly alleviated the subacute liver injury by competitively binding trp53inp1 via His224; the effect was better than those of the positive control drugs N-acetylcysteine (NAC) and disulfiram (DSF). In summary, the above results indicate that trp53inp1 is a key target for T-2 toxin to induce subacute liver injury and that inhibiting macrophage pyroptosis is a new method for treating liver injury. In addition, this study provides a new method and strategy for the discovery of key disease targets and the search for effective drugs.

Bryonia dioica Jacq., Evernia prunastri (L.) Ach., Telephium imperati L., and Aristolochia longa L. are species widely used in traditional medicine to treat several diseases including cancer. Conjugation of two or more extracts is an approach to improve the effectiveness of their pharmacological activities.

To evaluate the synergistic anticancer and anti-angiogenic effects of medicinal plants and edible species combinations.

In this work, B. dioica, E. prunastri, Telephium imperati, and Aristolochia longa extracts were conjugated to form four mixtures. The antiproliferative effect of mixtures on several carcinoma cells was examined by MTT assay, and the antiangiogenic activity was estimated through Hen's egg test in vivo. Moreover, in an Ovo model, 35 fertilized Ross eggs were used to test the embryotoxicity of mixtures.

At the highest concentration of 200 μg/mL, both mixtures exerted an important cytotoxic effect against human carcinoma cells. The mixture BETE (Bryonia Evernia Telephium Extract) significantly reduced HT-29, PC-3, and A-549 cell viability. Likewise, this mixture strongly suppressed vascularization in vivo at 200 μg/mL. Interestingly, no signs of toxicity on Perdix embryos were recorded within 21 days of treatment. More importantly, the mixture did not have any cytotoxic effect on non cancerous cells.

Taken together, our results suggest that the synergy between B. dioica, E. prunastri and T. imperati may be promising for developing new anti-cancer treatments.

In recent years, there has been a significant improvement in the accuracy of the classification of pigmented skin lesions using artificial intelligence algorithms. Intelligent analysis and classification systems are significantly superior to visual diagnostic methods used by dermatologists and oncologists. However, the application of such systems in clinical practice is severely limited due to a lack of generalizability and risks of potential misclassification. Successful implementation of artificial intelligence-based tools into clinicopathological practice requires a comprehensive study of the effectiveness and performance of existing models, as well as further promising areas for potential research development. The purpose of this systematic review is to investigate and evaluate the accuracy of artificial intelligence technologies for detecting malignant forms of pigmented skin lesions. For the study, 10,589 scientific research and review articles were selected from electronic scientific publishers, of which 171 articles were included in the presented systematic review. All selected scientific articles are distributed according to the proposed neural network algorithms from machine learning to multimodal intelligent architectures and are described in the corresponding sections of the manuscript. This research aims to explore automated skin cancer recognition systems, from simple machine learning algorithms to multimodal ensemble systems based on advanced encoder-decoder models, visual transformers (ViT), and generative and spiking neural networks. In addition, as a result of the analysis, future directions of research, prospects, and potential for further development of automated neural network systems for classifying pigmented skin lesions are discussed.