This study investigates the mycochemical profile and biological activities of hydroethanolic (EtOH), chloroform (CHCl3), and hot water (H2O) extracts of Sanghuangporus lonicerinus from Uzbekistan. Antioxidant capacity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), NO, and FRAP assays, and in vitro hypoglycaemic effects were evaluated through α-amylase and α-glucosidase inhibition. Antiproliferative potential was explored by analysing the binding affinities of EtOH and H2O extracts to estrogen receptor α (ERα), ERβ, androgen receptor (AR), and glucocorticoid receptor (GR), with molecular docking providing structural insights. LC-MS/MS analysis revealed solvent-dependent phenolic profiles, with the EtOH extract containing the highest total phenolic content (143.15 ± 6.70 mg GAE/g d.w.) and the best antioxidant capacity. The EtOH extract showed significant hypoglycaemic effects, with 85.29 ± 5.58% inhibition of α-glucosidase and 41.21 ± 0.79% inhibition of α-amylase. Moderate ERβ binding suggests potential for estrogen-mediated cancer therapy, while strong AKR1C3 inhibition by the EtOH extract supports its therapeutic potential.

Maize (Zea mays L.) is a vital crop worldwide, serving as a cornerstone for food security, livestock feed, and biofuel production. However, its cultivation is increasingly jeopardized by environmental challenges, notably soil salinization, which severely constrains growth, yield, and quality. To combat salinity stress, maize employs an array of adaptive mechanisms, including enhanced antioxidant enzyme activity and modulated plant hormone levels, which work synergistically to maintain reactive oxygen species (ROS) balance and ion homeostasis. This review explores the intricate interactions among ROS, antioxidant systems, plant hormones, and ion regulation in maize under salt stress, providing a comprehensive understanding of the physiological and molecular basis of its tolerance. By elucidating these mechanisms, this study contributes to the development of salt-tolerant maize varieties and informs innovative strategies to sustain agricultural productivity under adverse environmental conditions, offering significant theoretical insights into plant stress biology and practical solutions for achieving sustainable agriculture amidst global climate challenges.

The use of vegetable residues as a source of bioactive components is a global trend. The production of flours reintroduces these materials into the productive chain and extend their shelf-life. Processing may reduce the diversity of pigments present in the fresh matter. We analysed a beetroot peel flour (BPF) that presented relevant protein and fibre contents and preserved the colour of the in natura beetroot (Beta vulgaris L.) due to the presence of betacyanins and betaxanthins. The bioavailability, pharmacokinetics and mutagenicity of the pigments were predicted using bioinformatics. No mutagenicity was confirmed according to the OECD guidelines. A chemoprotective effect and cancer cell anti-clone activities were observed. BPF processing ensured a good nutritional value and maintained this product as a good source of bioactive compounds and of pigments with antitumor activity, suggesting this vegetable residue as a food industry pigments source for use in the elaboration of functional products.

Acute lung injury (ALI) represents a complicated and debilitating pulmonary disorder for which therapeutic options are currently limited. Genipin is an aglycone derived from the geniposide, the most abundant iridoid glucoside constituent of Gardenia jasminoides Ellis, and has demonstrated beneficial effects in ALI. The objective of this study was to investigate the protective effect of Gen-17, a beta-methyl derivative of genipin, against ALI in vitro and in vivo, and explore its mechanism of action.

In this study, we prepared a beta-methyl derivative of genipin, Gen-17, and assessed the antioxidative and anti-inflammatory effects of Gen-17 in LPS-induced murine macrophages and ALI in mice, and explored the mechanism of action of Gen-17. In an in vivo model, the impact of Gen-17 on lipopolysaccharide (LPS)-induced ALI in mice was investigated by assessing pro-inflammatory cytokine levels, lung histology, edema, and vascular and alveolar barrier integrity, and in an in vitro model, murine macrophages-Raw 264.7 cells were used to establish a cell model of inflammation and oxidative stress by incubating with LPS. Keap1-Nrf2/HO-1, NF-κB and MAPK signaling pathways related factors were tested in vitro and in vivo to explore the possible mechanism of Gen-17.

The study showed that administration of Gen-17 conferred protection against LPS-induced ALI in mice, characterized by the mitigation of histological lung tissue alterations, reduction in lung edema, diminished protein content in bronchoalveolar lavage fluid, attenuation of inflammatory cell infiltration, and a decrease in cytokine secretion. Furthermore, Gen-17 exhibited the capacity to inhibit the nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) in the context of LPS-induced lung injury. In vitro, research findings revealed that Gen-17 demonstrated notable efficacy in reducing oxidative stress and inflammation in RAW 264.7 cells induced by LPS. Its central mechanism of action revolved around enhancing the antioxidant defense pathway, mediated through nuclear factor erythroid 2-related factor 2 (Nrf2). Consequently, this intervention repressed the release of pro-inflammatory mediators initiated by LPS, along with the modulation of the mitogen-activated protein kinase (MAPK) signaling pathway.

Gen-17 demonstrates the ability to mitigate oxidative stress and inflammation in the context of LPS-induced ALI via modulation of the MAPK, NF-κBp65, and Keap1/Nrf2/heme oxygenase-1 (HO-1) pathways. As such, it emerges as a promising and novel therapeutic candidate for treating ALI.

Opioids have been extensively used in cancer pain management because they can significantly improve the quality of life of patients with advanced cancer. However, recent evidence suggests that opioids can also modulate the tumor immune microenvironment by interacting with opioid receptors on immune cells, potentially regulating tumor progression and efficacy of cancer treatments. Notably, morphine can exhibit a dose-dependent effect on tumor immunity in pancreatic cancer and renal cell models, with lower doses potentially promoting tumor migration and invasion of pancreatic cancer cells, whereas higher doses shows the effect of inhibiting migration and invasion through distinct molecular pathways. The present review therefore comprehensively explored the mechanisms by which opioids can regulate the tumor immune microenvironment, focusing on their effects on immune cells, oxidative stress and angiogenesis. It also examined the interactions between opioids and other analgesics, along with their potential impact on immune modulation. All relevant articles and materials were retrieved from PubMed using the key words 'opioids', 'immune system', 'T cells', 'monocytes', 'macrophages', 'lymphocytes', 'natural killer cell', 'immunotherapy', 'immune cell function' and 'dose dependent effect'. The immunosuppressive effects of opioids, particularly through the µ-opioid receptor, can suppress the activity of natural killer cells, impair antigen presentation and promote the function of regulatory T cells (Tregs). These effects may contribute to tumor progression and metastasis. The severity of these immunosuppressive effects appears to be dose-dependent and can vary among different tumor types. There is evidence to suggest that tumors with higher immune responsiveness will experience more pronounced suppression, including the reduction of tumor angiogenesis, resulting in a decrease in tumor volume and decrease in tumor metastases. Furthermore, the combination of opioids with other analgesics, such as non-steroidal anti-inflammatory drugs, has the potential to exacerbate immunosuppression, which can in turn increase the risk of infections. Therefore, although opioids are essential for pain management in patients with cancer, their potential to modulate the immune microenvironment and promote tumor progression requires careful consideration. Clinicians should evaluate the advantages and disadvantages of opioids, especially regarding emerging immunotherapies, to minimize their potential negative effects on the outcomes of cancer treatments. Future studies are recommended to prioritize the development of strategies that optimize pain management whilst preserving immune function, such as receptor-specific opioid formulations or adjunctive therapies targeting immunosuppressive pathways.

8-hydroxy-2'deoxyguanosine (8-OHdG) is an oxidative product removed from DNA following radical oxygen species-induced damage. As a water-soluble molecule, it can be measured non-invasively in urine and is commonly used as a marker for 'whole-body' oxidative stress. However, its validity and reliability in assessing oxidative stress across various chronic diseases and in early carcinogenesis screening in clinical diagnosis and research remain subjects of debate. To determine optimal measurement timing and duration, it is essential to establish the circadian profile of 8-OHdG under everyday life conditions. Here, applying the integrative single-case design, we show the presence of day-night differences for 8-OHdG in continuous time series of two breast cancer survivors while considering different correction approaches. The participants sampled their urine in 12-h-pooled collections over one month. In both subjects, 8-OHdG levels were significantly higher during the day than at night regardless of whether they were corrected by creatinine or urine volume (creatinine corrected: t = -6.43, p < 0.01 [subject 1], t = -2.69, p = 0.01 [subject 2]; volume corrected: t = -7.30, p < 0.01 [subject 1], t = -3.69, p < 0.01 [subject 2]). Notably, urinary 8-OHdG levels show higher variability in night samples compared to day samples. These findings underscore the importance of considering daily fluctuations in 8-OHdG levels in both clinical and research studies, as well as the need to account for the dynamic characteristics of stress markers to minimize the risk of inconsistent or misleading results in clinical diagnostics.

The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines. Cell viability, migration, and clonogenicity were assessed using the following assays MTT, scratch, and colony formation. Antioxidant levels of GSH, as well as activities catalase (CAT), and superoxide dismutase (SOD) were measured. BSO alone exhibited minimal cytotoxic effects, while DOX alone reduced cell viability significantly. The combination of BSO+DOX decreased IC50 values for most cell lines, demonstrating a synergistic effect, especially in B16/F10, S180, and SVEC4-10 cells. BSO+DOX combination significantly inhibited cell migration and clonogenicity compared to DOX alone. While GSH levels were decreased with BSO+DOX treatment activities of CAT and SOD increased following DOX administration but remained unchanged by BSO. These results suggest that BSO may be considered a valuable tool to improve DOX therapeutic efficacy, particularly in cases of chemotherapy-resistant tumors, as BSO enhances DOX activity while potentially reducing systemic chemotherapeutic drug toxicity.

According to the World Health Organization, cancer remains the primary cause of death of millions of individuals annually and the foremost cause of mortality worldwide. Cancer imposes substantial economic and mental challenges on patients and their families and strains healthcare systems. Depression, one of the most prevalent mental health conditions, affects approximately 3.8% of the global population and is a significant global health challenge. Research indicates increasing incidence rates of depression among patients with cancer. Depression also appears to influence cancer development and progression, worsening patient prognosis and quality of life, thereby creating additional challenges for clinical treatment. Correlation of depression and cancer is a complicated yet promising field with fast-paced progression and vital clinical values. Therefore, we discussed in this review the associations between depression and cancer and their potential mechanisms by analyzing the specific role of depression in the development and progression of tumors from the perspective of suppressing tumor immunity, inhibiting tumor cell apoptosis, inducing DNA damage, promoting tumor cell mesenchymal transition, enhancing tumor cell stemness, and promoting tumor angiogenesis. This review also discusses how tumors influence the development of depression via inflammatory factors and the significance of identifying and treating depression to enhance the quality of life and prognosis of patients with cancer. Promising biomarkers and effective treatments are also highlighted. Despite available data, limited research exists on how treating depression affects cancer prognosis, and whether timely treatment can reduce cancer risk remains unclear, which necessitates further investigation. This review summarizes the molecular mechanisms involved in the relationship between cancer and depression to help identify new biomarkers and provide precise medical care for patients with depression. We hope this review will lay the foundation for future research, advancing new biomarkers and therapies for early diagnosis of cancer and depression comorbidity.

Bisphenol S (BPS) and Bisphenol F (BPF), as alternatives to bisphenol A (BPA), are recognized for their endocrine-disrupting properties, but their combined immune toxicity mechanisms remain poorly understood. This study systematically evaluates the individual and joint immune toxicity effects of BPS and BPF through ADMET predictions, transgenic zebrafish models, and molecular docking analyses. The results indicate that equal effect concentration BPS and BPF act through distinct immune pathways: BPS primarily targets macrophages to mediate immune responses, while BPF significantly stimulates neutrophil proliferation and induces a stronger inflammatory response through chemokine signaling. Molecular docking studies show that BPF binds more stably to pro-apoptotic protein Mapk8 and oxidative stress-related protein Hsp90aa1, leading to significantly higher levels of apoptosis and reactive oxygen species (ROS) compared to BPS. The similarity of modes of action (MOA)between BPS and BPF based on relevant immune indicators calculated and experimentally is about 0.3; this quantitative result also proves that modes of action differ widely. Nonetheless, most of the indicators showed superimposed effects in the combined experiments, and it is noteworthy that the oxidative stress indicators (SOD, MDA) showed synergistic effects, suggesting that BPS and BPF, which have very different modes of action, are able to be risk assessed using an additive model with respect to immunity, but may exhibit synergistic risks with respect to oxidative stress. This research demonstrates that BPS and BPF induce immune toxicity via different molecular targets and pathways and highlights the need to account for their synergistic effects in risk assessments. These findings provide important insights into the immune toxicity mechanisms of BPA substitutes and the potential risks of combined exposures.

Colorectal cancer (CRC) is a common type of cancer that impacts the digestive tract, and current treatment options have limitations. Studies have confirmed that ferroptosis plays a key role in CRC progression. This research sought to clarify how Proline-rich acidic protein 1 (PRAP1) influences CRC advancement and ferroptosis, and to uncover the underlying mechanisms involved.

Real-time quantitative PCR (RT-qPCR) and western blot were employed to ascertain the levels of PRAP1 in CRC cells (SW480, SW620, and LOVO) and tissues. Immunofluorescence was utilized to locate PRAP1. Biological characterization of CRC cells was determined through CCK-8 assay, EdU staining, Transwell assay, TUNEL staining and Scratch-wound assay. Iron and Fe2+ content was measured using prussian blue staining and iron assay kit. A nude mouse model of xenograft was established, and the impact of PRAP1 on tumor growth was investigated by pathological staining. Expression of ferroptosis-related proteins as well as nuclear factor-erythroid factor 2-related factor 2 (Nrf2) pathway proteins was detected by Western blot.

PRAP1 levels were elevated in CRC. Overexpression PRAP1 promoted cell proliferation, inhibited apoptosis and ferroptosis. Additionally, overexpression PRAP1 can activate the Nrf2 pathway. However, silencing PRAP1 had the opposite effect. In vivo tumor xenograft experiments showed that silencing PRAP1 resulted in decreased Ki67 positivity and increased TUNEL positivity in tumor tissues, and blocked Nrf2 pathway, thereby inhibited tumor growth.

PRAP1 promotes CRC cell proliferation and inhibits ferroptosis by Nrf2 pathway. This study provides a conceptual framework for the development of novel targeted drugs.

Background and ObjectiveThe rapid proliferation of mobile technology has intensified debates on the potential adverse effects of non-ionizing electromagnetic radiation (NIER) from mobile phones on various human organs and cells. This study aimed to evaluate the impact of mobile phone-emitted NIER on parotid gland function.MethodologyThis cross-sectional study included 104 student volunteers from the University campus, categorized based on their mobile phone usage and exposure duration. Saliva samples were collected from the dominant (test) and non-dominant (control) sides. Key metrics measured were salivary flow rate, pH, albumin, Ischemia-Modified Albumin (IMA), and the IMA/albumin ratio (IMAR). Data analysis was performed using one-way ANOVA and Fisher's LSD multiple comparisons, with p ≤ 0.05 considered statistically significant.ResultsThe salivary flow rate and pH were higher on both sides in all groups, correlating with increased mobile phone usage duration. Although albumin levels were lower on the dominant side, they increased with longer mobile phone use. Salivary IMA and IMAR were higher on the dominant side in subjects using mobile phones for ≤3 years compared to those using them for >3 years.Interpretation and ConclusionConsistent exposure to NIER and the heat generated by mobile phones adversely affects parotid gland function, as indicated by increased salivary flow rate, pH, and altered levels of albumin, IMA, and IMAR. Public health recommendations should encourage reducing long-duration conversations and using earphones to minimize NIER exposure. Further studies are needed to evaluate the long-term effects of NIER on parotid gland function.

Wheat bran, rich in phenolic compounds like ferulic acid, possesses notable antioxidant properties that may contribute to cancer treatment strategies. This study examined the effects of hydrolyzed arabinoxylan oligomers (HAOs) linked with ferulic acid from hard wheat bran on three human cancer cell lines: colon cancer (SW480), liver cancer (HepG2), and cervical cancer (HeLa). Cells were cultured in a three-dimensional (3D) 0.5% PGS matrix and exposed to varying concentrations (100, 500, and 1000 μg/mL) of wheat bran antioxidants (WBA) extracts. Results show that WBA inhibited growth of SW480 cells, significantly reducing spheroid expansion and promoting dehydration. In contrast, HepG2 cells exhibited increased growth under WBA treatment, suggesting a non-toxic, growth-enhancing effect. No significant changes were observed in HeLa cell growth, with cell viability remaining high across all treatments. These findings highlight the selective influence of WBA on cancer cell behavior, underscoring its potential for targeted, personalized cancer therapies. This study provides valuable insights into the application of antioxidant-rich compounds for modulating specific cancer cell dynamics, paving the way for novel therapeutic approaches.

Macrophages are heterogeneous cells that are the mediators of tissue homeostasis. These immune cells originated from monocytes and are classified into two basic categories, M1 and M2 macrophages. M1 macrophages exhibit anti-tumorous inflammatory reactions due to the behavior of phagocytosis. M2 macrophages or tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and have a basic role in tumor progression by interacting with other immune cells in TME. By the expression of various cytokines, chemokines, and growth factors, TAMs lead to strengthening tumor cell proliferation, angiogenesis, and suppression of the immune system which further support invasion and metastasis. This review discusses recent and updated mechanisms regarding tumor progression by M2 macrophages. Moreover, the current therapeutic approaches targeting TAMs, their advantages, and limitations are also summarized, and further treatment approaches are outlined along with an elaboration of the tumor regression role of macrophages. This comprehensive review article possibly helps to understand the mechanisms underlying the tumor progression and regression role of macrophages in a comparative way from a basic level to the advanced one.

Objective: Acute traumatic muscle injuries are common and result in substantial loss of time and risk of recurrence. Pulsed radiofrequency (PR) is a strategy that has been gradually adopted for treating muscle injuries in clinical practice. However, the molecular mechanism underlying its therapeutic effects is currently unclear. Materials and Methods: In this study, we screened the gene expression profiles of rats with muscle contusion obtained from the online dataset GSE162565. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the differentially expressed genes were conducted. Further, we established an acute soft tissue injury (ASTI) rat model and applied PR treatment. Muscle swelling rate analysis, malondialdehyde (MAD) and superoxide dismutase (SOD) content, inflammatory cytokine release, and hematoxylin and eosin staining of the gastrocnemius muscles of ASTI and ASTI + PR rats were performed, and the results were compared with those of control rats. Further, we evaluated the gene expression of Ccl1, interleukin-6 (IL-6), nuclear factor-kappa-B-inhibitor alpha (Nfkbia), Akt1, Jun, Fos, and Caps3 in the model and PR-treated groups, all of which are key genes in the tumor necrosis factor (TNF)/mechanistic target of rapamycin (mTOR) signaling pathway according to the KEGG analysis. Results: The results revealed that 52 genes involved in the TNF/mTOR signaling pathway were closely associated with ASTI progression in rats. PR treatment significantly reduced the malondialdehyde content but increased the SOD content in ASTI model rat muscles, efficiently alleviated muscle contusions and reduced TNF-α and IL-1β production. Moreover, PR treatment significantly decreased Ccl1, IL-6, and Nfkbia expression but increased Akt1, Jun, Fos, and Caps3 levels in ASTI models. These data indicate that PR alleviated ASTI in rats by mediating redox homeostasis and the inflammatory response, which might be modulated by the TNF/mTOR signaling pathway. Conclusions: Thus, this study contributes to the understanding of ASTI progression and provides more substantial information about the genetic mechanism underlying the therapeutic effects of PR on ASTI.

Lung cancer is the primary cause of death due to cancer all over the world despite the decrease in the mortality rates from cancer in general. While chemotherapy is a commonly employed treatment for lung cancer, its efficacy is limited due to poor tissue selectivity, inadequate delivery to tumor sites, and associated side effects. The present work aims to assess the potential anti-cancer effectiveness of amlodipine, a calcium channel blocker, on murine lung cancer via modulating GSK-3β, NF-κB, PPARγ, and apoptosis. Lung cancer was induced in BALB/c mice by intraperitoneal injection of 1.5 g/kg in two doses of urethane: once on the 1st and the second on the 60th day of the experiment. Amlodipine was administered orally at a dose of 10 mg/kg/day for the last 28 days of experiment. Relative to urethane group, amlodipine mitigated urethane-induced histopathological abnormalities. It restored oxidant/antioxidant balance by normalizing MDA, GSH, and SOD. Furthermore, it exerted a marked anti-inflammatory effect through downregulating lung MPO, ICAM-1, IL-6, TNF-α, and NF-қB expressions. Amlodipine enhanced apoptosis of cancer cells as evidenced by increasing Bax and decreasing Bcl-2 expression. The anticancer effect of amlodipine was suggested to be mediated through increasing PPARγ and reducing GSK3β and p-GSK3β signaling. Collectively, these results suggest that amlodipine could exert a promising anticancer effect against lung cancer through modulating GSK-3β, NF-κB, PPARγ, and apoptosis. Our findings could be highly significant in clinical settings, offering a valuable adjuvant option for managing lung carcinoma, particularly in patients with cardiovascular disorders.

Acrylamide (ACR) has garnered significant attention due to its neurotoxic effects. Oxidative stress, a key mechanism underlying ACR-induced neurotoxicity, is well-documented. Methionine sulfoxide reductase A (MsrA) plays a pivotal role in protecting various types of cells, including neuronal cells, against the effects of oxidative stress. However, the role of MsrA in ACR-induced neurotoxicity remains poorly understood. This study explored the effects of MsrA on ACR-induced neurotoxicity. After administering ACR by gavage at doses of 20 mg/kg, 30 mg/kg, and 40 mg/kg for 21 days, rats exhibited motor impairment and structural damage in the cerebellum. Both in vivo and in vitro, ACR dose-dependently reduced MsrA level, accompanied by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, c-Jun N-terminal kinase (JNK) phosphorylation, and mitochondria-dependent neuronal apoptosis. To further ascertain the role of MsrA in mitigating ACR-induced neuronal apoptosis, SH-SY5Y cell line overexpressing MsrA was constructed. Overexpression of MsrA attenuated the ACR-induced increases in ROS and MDA levels. Additionally, alterations in mitochondrial membrane potential (MMP), mitochondrial ultrastructure, JNK phosphorylation, and mitochondria-dependent apoptosis caused by ACR were reversed in the cells overexpressing MsrA. These findings offer significant insights into the protective role of MsrA against ACR-induced neurotoxicity.

Chitinase 3-like 1 (CHI3L1) has been implicated in the pathogenesis of various diseases, including cancer. In our previous study, we found that anti-CHIL1 antibody inhibited lung tumorigenesis. It has been reported that CHI3L1 is highly overexpressed in colon cancer tissue compared with normal tissue, and high levels of serum CHI3L1 have been associated with worse colon cancer prognosis. We investigated the anticancer effect of an anti-CHI3L1 antibody on colon cancer cells. The anti-CHI3L1 antibody inhibited the cell growth of colon cancer cells in a concentration-dependent manner. The anti-CHI3L1 antibody also reduced the migration but increased apoptotic cell death in colon cancer cells. Using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), we identified an association between VEGFA and CHI3L1 in colon cancer. We confirmed interaction between VEGFA and CHI3L1 through immunoprecipitation. Furthermore, the combination treatment of the anti-CHI3L1 antibody and VEGFA siRNA inhibited cell growth but increased apoptotic cell death. Additionally, using the Human Base database, we found that CHI3L1 and VEGFA are associated with nicotinamide phosphoribosyltransferase (NAMPT). Furthermore, combining the anti-CHI3L1 antibody and NAMPT siRNA more effectively reduced cell growth and the expression of CHI3L1, VEGFA, and cell growth-related proteins, but significantly increased apoptosis-related proteins. The combination of VEGFA siRNA and NAMPT siRNA more effectively inhibited cell growth. Anti-CHI3L1 antibody inhibited the production of ATP and NADH in colon cancer and had a higher inhibitory effect on these levels when combined with NAMPT siRNA These data demonstrated that anti-CHI3L1 antibody is useful as a potential therapy for colon cancer by inhibiting NAMPT-dependent VEGFA expression and ATP and NADH levels.

To evaluate curcumin's impact on postmenopausal women's health through a meta-analysis. The databases searched included PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2024. The Cochrane risk of Bias assessment tool was used to assess the quality of the included studies. This meta-analysis reviewed 14 randomized controlled trials involving 982 participants (466 in the intervention group and 516 in the control group) and evaluated curcumin's effects across 30 indicators grouped into cardiovascular health, oxidative stress and antioxidant markers, bone health, metabolic health, and quality of life. We found that curcumin reduced systolic (SMD -0.51, 95% CI -0.83 to 0.19, p = 0.002) and diastolic blood pressure (SMD -0.63, 95% CI -0.96 to -0.30, p = 0.005), increased total antioxidant capacity (SMD 0.93, 95% CI 0.15 to 1.72, p = 0.020) and superoxide dismutase levels (SMD 0.30, 95% CI 0.04 to 0.56, p = 0.026), decreased aspartate aminotransferase (AST) (SMD -0.36, 95% CI -0.66 to -0.06, p = 0.020), and improved vasomotor (SMD -0.39, 95% CI -0.65 to -0.13, p = 0.003) symptoms. Curcumin positively impacts several indicators in postmenopausal women, highlighting its potential therapeutic role in managing cardiovascular risk factors, oxidative stress, hepatoprotective effects, and vasomotor symptoms. Due to variations in the purity and dosages across different studies and the lack of combinable data for certain indicators, the conclusions are still limited. These issues can be addressed through more comprehensive large-scale trials later. A more in-depth investigation into the mechanisms is also crucial.

Ficus benjamina is a common park tree, with previous reports of some medicinal properties. In this work, we identified and explored phytochemicals from F. benjamina for potential antimicrobial, pro-wound-healing, anti-inflammatory, and effect on cancer cell lines' proliferation, both experimentally and bioinformatically. Gas chromatography/mass spectrometry (GC/MS) analysis was performed to identify the volatile compounds. The nonvolatile active components of the extract were identified by HPLC and LC-ESI-MS. We found that some drug-resistant microorganisms (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Serratia marcescens, and Salmonella enteritidis) were inhibited by the extract, the 80% fraction, and all the identified flavonoids except quercetin 3-O-rutinoside. Furthermore, the extract and above-mentioned compound also inhibited the growth of biofilm-producing bacterium. The extract and 80% fraction were very potent (p < 0.001) at inducing death of MCF7 and U87 cancer cell cultures and were more effective in that than the chemotherapeutic agent doxorubicin which served as a positive control. Additionally, the extract of F. benjamina, the 80% fraction, and selected phytochemicals had pronounced pro-wound-healing properties. Finally, the extracts, the 80% fraction, caffeic acid, kaempferol 3-O-rutinoside, and kaempferol 3-O-robinobioside significantly inhibited the secretion of pro-inflammatory cytokines, IL-6 and IL-8 (p < 0.001). In conclusion, this comprehensive research revealed convincing and promising indications of significant therapeutic potential of a F. benjamina extract and its active phytochemicals.

Disulfidptosis, a regulated cell death modality driven by the cystine transporter solute carrier family 7 member 11 (SLC7A11), is characterized by actin cytoskeleton collapse under glucose starvation. This review systematically elucidates the pivotal role of disulfidptosis in tumor metabolic reprogramming, with a focus on its molecular mechanisms and distinctions from other cell death pathways. The core mechanisms include SLC7A11-mediated cystine overload and NRF2/c-Myc-regulated pentose phosphate pathway activation. By integrating multiomics data and single-cell transcriptomics, we comprehensively decipher the heterogeneous expression patterns of disulfidptosis-related genes (DRGs) and their dynamic interplay with immune microenvironment remodeling. Furthermore, the coexpression networks of DRGs and disulfidptosis-related long noncoding RNAs (DRLs) offer novel insights into tumor diagnosis, prognosis, and targeted therapy. Therapeutically, SLC7A11 inhibitors (e.g., HG106) and glucose transporter inhibitors (e.g., BAY-876) demonstrate efficacy by exploiting metabolic vulnerabilities, whereas natural compounds synergizing with immune checkpoint blockade provide strategies to counteract immunosuppressive microenvironments. Through interdisciplinary collaboration and clinical translation, disulfidptosis research holds transformative potential in redefining precision oncology.

Cancer treatments often exploit oxidative stress to selectively kill tumour cells by disrupting their lipid peroxidation membranes and inhibiting antioxidant enzymes. However, lipid peroxidation plays a dual role in cancer progression, acting as both a tumour promoter and a suppressor. Balancing oxidative stress through antioxidant therapy remains a challenge, as excessive antioxidant activity may compromise the efficacy of chemotherapy and radiotherapy.

This review explores the role of antioxidants in mitigating lipid peroxidation in cancer therapy while maintaining treatment efficacy. It highlights recent advancements in nanotechnology-based targeted antioxidant delivery to optimize therapeutic outcomes.

A comprehensive literature review was conducted using reputable databases, including PubMed, Scopus, Web of Science, and ScienceDirect. The search focused on publications from the past five years (2020-2025), supplemented by relevant studies from earlier years. Keywords such as "antioxidants," "lipid peroxidation," "nanotechnology in cancer therapy," and "oxidative stress" were utilized. Relevant articles were critically analysed, and graphical illustrations were created.

Emerging evidence suggests that nanoparticles, including liposomes, polymeric nanoparticles, metal-organic frameworks, and others, can effectively encapsulate and control the release of antioxidants in tumour cells while minimizing systemic toxicity. Stimuli-responsive carriers with tumour-specific targeting mechanisms further enhance antioxidant delivery. Studies indicate that these strategies help preserve normal cells, mitigate oxidative stress-related damage, and improve treatment efficacy. However, challenges such as bioavailability, stability, and potential interactions with standard therapies remain.

Integrating nanotechnology with antioxidant-based interventions presents a promising approach for optimizing cancer therapy. Future research should focus on refining lipid peroxidation modulation strategies, assessing oxidative stress profiles during treatment, and employing biomarkers to determine optimal antioxidant dosing. A balanced approach to antioxidant use may enhance therapeutic efficacy while minimizing adverse effects.

This case report presents a unique study focused on relationship between nutritional parameters, C-reactive protein (CRP), and the marker of oxidative stress 8-hydroxy-2'-deoxyguanosine (8-OHdG), in 61-year-old male paraplegic patient with multiple pressure ulcers. A multidisciplinary approach was essential for the timing of the successful reconstruction process. The patient had a history of paraplegia since 1999 due to a skiing accident with fractures of thoracic vertebrae (Th6-Th9), requiring spinal surgery. His medical background includes acute pancreatitis with biliary tract revisions, partial pancreatic resection, acute respiratory failure with tracheostomy, renal failure treated with hemodialysis, bronchopneumonia, pseudomembranous colitis, and hyperuricemia. The patient also underwent multiple surgical interventions, including treatment for ulnar nerve paresis, cholecystectomy, and multiple pressure ulcer reconstructions. The study describes the relationship between selected biochemical parameters and overall clinical status in a paraplegic patient with three deep pressure ulcers located in the left-sided ischial, trochanteric, and sacral regions during their multistage surgical therapy. The reconstructive procedure and collection of biological samples for determination of selected biochemical parameters were performed according to the same schedule: debridement of pressure ulcers at the beginning of the particular hospitalization and on the day of surgical reconstruction. The patient's severe condition was accompanied by decreased levels of both 8-OHdG and selected nutritional parameters (albumin, prealbumin, and total protein) and increased CRP levels at the beginning of the treatment process. The evaluation of the dynamics of the measured parameters during the gradual improvement of the patient's condition and the multistage reconstruction of pressure ulcers in six hospitalizations over a period of 17 months was continued resulting in the healing of all pressure ulcers. This case highlights the crucial importance of investigating selected biochemical parameters, with emphasis on 8-OHdG, and nutritional parameters, for the timing of surgical strategy and comprehensive therapy in patients with multiple pressure ulcers and severe, complex medical histories.

This study investigated the suppressor effects of carrots depending on cultivation method on AOM/DSS-induced colon cancer in mice by examining cell apoptosis, inflammation response, and metabolites. Carrots grown using different fertilizers significantly suppressed tumor development by modulating cell apoptosis and inflammatory responses in our experimental settings.

Naturaldream Fertilizer Carrot (NFC) cultivated with deep sea water minerals (DSWM) showed effectively increased the expression of apoptosis-related genes and proteins including p53, p21, Bim, Bad, Bax, Bak, Caspase 9, and Caspase 3 in colon tissue, while inhibiting the production of inflammatory factors and related genes and proteins such as TNF-a, IL-1b, IL-6, IFN-g, NF-kB, and iNOS in serum, spleen cells, and liver tissues. Intestinal microbiota analysis revealed a distinct composition in mice receiving carrots compared to the control group, with accumulation of intestinal microorganisms such as Lachnospiraceae, and Mucispirillum schaedleri closely associated with anti-tumor effects.

Overall, our results indicate that carrots, especially carrots grown with DSWM fertilizers, play a crucial role in inhibiting AOM/DSS-induced colon cancer in mice by regulating cell apoptosis and inflammation responses. The present findings provide valuable insights for further exploration of carrots depending on the cultivation method, as a potential dietary source against colon cancer.

Serious pulmonary pathologies of infectious, viral, or bacterial origin are accompanied by inflammation and an increase in oxidative stress (OS). In these situations, biological measurements of OS are technically difficult to obtain, and their results are difficult to interpret. OS assays that do not require complex preanalytical methods, as well as machine learning methods for improving interpretation of the results, would be very useful tools for medical and care teams.

We aimed to identify relevant OS biomarkers associated with the severity of hospitalized patients' condition and identify possible correlations between OS biomarkers and the clinical status of hospitalized patients with COVID-19 and severe lung disease at the time of hospital admission.

All adult patients hospitalized with COVID-19 at the Infirmerie Protestante (Lyon, France) from February 9, 2022, to May 18, 2022, were included, regardless of the care service they used, during the respiratory infectious COVID-19 epidemic. We collected serous biomarkers from the patients (zinc [Zn], copper [Cu], Cu/Zn ratio, selenium, uric acid, high-sensitivity C-reactive protein [hs-CRP], oxidized low-density lipoprotein, glutathione peroxidase, glutathione reductase, and thiols), as well as demographic variables and comorbidities. A support vector machine (SVM) model was used to predict the severity of the patients' condition based on the collected data as a training set.

A total of 28 patients were included: 8 were asymptomatic at admission (grade 0), 14 had mild to moderate symptoms (grade 1) and 6 had severe to critical symptoms (grade 3). As the first outcome, we found that 3 biomarkers of OS were associated with severity (Zn, Cu/Zn ratio, and thiols), especially between grades 0 and 1 and between grades 0 and 2. As a second outcome, we found that the SVM model could predict the level of severity based on a biological analysis of the level of OS, with only 7% misclassification on the training dataset. As an illustrative example, we simulated 3 different biological profiles (named A, B, and C) and submitted them to the SVM model. Profile B had significantly high Zn, low hs-CRP, a low Cu/Zn ratio, and high thiols, corresponding to grade 0. Profile C had low Zn, low selenium, high oxidized low-density lipoprotein, high glutathione peroxidase, a low Cu/Zn ratio, and low glutathione reductase, corresponding to grade 2.

The level of severity of pulmonary damage in patients hospitalized with COVID-19 was predicted using an SVM model; moderate to severe symptoms in patients were associated with low Zn, low plasma thiol, increased hs-CRP, and an increased Cu/Zn ratio among a panel of 10 biomarkers of OS. Since this panel does not require a complex preanalytical method, it can be used and studied in other pathologies associated with OS, such as infectious pathologies or chronic diseases.

Colorectal cancer is the third most common cancer worldwide; its higher incidence in the Western world, compared to rural areas of Africa and Asia, led to its classification among the so-called Westernized diseases. The wild strawberry Fragaria vesca L. is endowed with several bioactive components, such as polyphenols, vitamins, terpenes, and organic acids that can contribute to cancer prevention. In this study, we chemically characterized a wild strawberry extract through high-resolution mass spectrometry and evaluated its antioxidant properties on two human colorectal cancer cell lines: KRAS mutated SW480 cells and E705 cells. We found that treatment with the extract induced cell cycle arrest in the G2 phase in SW480 cells, while it led E705 cells to apoptosis through a significant increase in the reactive oxygen species level. Wild strawberry extract is a promising dietary supplement for both wild-type and KRAS-mutated patients who exhibit a more aggressive cancer phenotype. In addition, the lack of toxicity of wild strawberry extract toward healthy colorectal cells makes this food a promising chemopreventive nutritional supplement.

The biphasic dose-response behavior, also known as hormesis, is a characteristic feature of numerous natural products. It is defined by beneficial effects at low concentrations and toxicity at higher doses. This study investigates the hormetic effects of Brosimine B, a flavonoid derived from Brosimum acutifolium, on retinal cell viability under oxidative stress.

To simulate ischemic conditions, we used an oxygen-glucose deprivation (OGD) model. Retinal cells were treated with varying concentrations of Brosimine B, and analyses of cell viability, reactive oxygen species (ROS) production, and antioxidant enzyme activity were performed.

Brosimine B at 10 µM significantly enhanced cell viability and reduced ROS production, likely through modulation of oxidative stress-protective enzymes such as catalase. However, higher concentrations (>10 µM) induced cytotoxic effects. A computational modeling approach using a hormetic (inverted U-shaped) model revealed biologically interpretable parameters, including a peak response at 10.2 µM and a hormetic zone width (σ = 6.5 µM) (R2 = 0.984).

These results confirm that Brosimine B exhibits hormetic neuroprotective effects within a well-defined concentration window, supporting its potential as a therapeutic agent for oxidative stress-related retinal damage. The study highlights the value of computational modeling in optimizing dose-response analyses, offering a framework for refining natural product therapies and predicting toxicological thresholds in pharmacological applications.

Malignant melanoma, particularly amelanotic melanoma, contributes to a very serious problem in public health. One way to find new therapies is to learn about and understand the molecular pathways that regulate cancer growth and development. In the case of a tumor, the autophagy process can lead to the development or inhibition of cancer. This study aimed to assess the cytotoxicity of connection trametinib (MEK1 and MEK2 kinase inhibitor) with autophagy inhibitors-chloroquine (lysosomal clearance of autophagosomes inhibitor) and 3-methyladenine (phosphatidylinositol 3-kinases inhibitor), on two amelanotic melanoma cell lines (C32 and A-375). The results showed that combination therapy had better anti-proliferative effects than alone therapy in both cell lines. The C32 cell line was more sensitive to 3-methyladenine treatment (alone and in combinations), and the A375 line showed sensitivity to chloroquine and 3-methyladenine (alone and in combinations). The anti-proliferative effect was accompanied by dysregulation of the cell cycle, a decrease in the reduced thiols, the depolarization of the mitochondrial membrane and the level of p44/p42 MAPK. Both inhibitors have the ability to induce apoptosis. Differences in the level of LC3A/B and LC3B proteins between the chloroquine and the 3-methyladenine samples indicate that these drugs inhibit autophagy at different stages. The enhancement of the effect of trametinib by autophagy inhibitors suggests the possibility of combining drugs with anti-cancer potential with modulators of the autophagy process.

Prolonging the duration of photodynamic therapy (PDT) enhances the level of reactive oxygen species (ROS), thereby facilitating tumor ablation. However, our findings indicated that excessive ROS not only induces epithelial-mesenchymal transition (EMT) but also creates an immunosuppressive microenvironment in tumor, thereby triggering tumor metastasis.

We initially developed neutrophil membrane hybrid liposomes (NLs) that can specifically target inflamed tumor tissues following PDT. Then, we utilized NLs to encapsulate the antioxidant nanozyme FeGA and the antiplatelet drug Lysine Acetylsalicylate (LAS), resulting in the formulation NLASF.

Experimental results demonstrated that FeGA effectively scavenges ROS, thereby reversing the immunosuppressive microenvironment induced by prolonged PDT. Furthermore, the incorporation of LAS effectively disrupts the interaction between tumor cells and platelets, mitigating tumor EMT and inhibiting hematogenous tumor metastasis. In a breast cancer mouse model, we observed that treatment with NLASF led to a near-complete suppression of tumor lung metastasis following the prolonged PDT. Additionally, the in vivo application of NLASF did not result in any blood toxicity or organ toxicity, highlighting its significant advantages over the free drugs group.

This study provides a novel approach to enhance the efficacy of PDT and successfully suppress PDT-mediated tumor metastasis.

The endonucleolytic cleavage step of the eukaryotic mRNA 3'-end processing is considered imprecise, which leads to heterogeneity of cleavage site (CS) with hitherto unknown function. Contrary to popular belief, we show that this imprecision in the cleavage is tightly regulated, resulting in the CS heterogeneity (CSH) that controls gene expression in antioxidant response. CSH centres around a primary CS, followed by several subsidiary cleavages determined by CS's positions. Globally and using reporter antioxidant mRNA, we discovered an inverse relationship between the number of CS and the gene expression, with the primary CS exhibiting the highest cleavage efficiency. Strikingly, reducing CSH and increasing primary CS usage induces gene expression. Under oxidative stress (we employ three conditions that induce antioxidant response, tBHQ, H2O2, and NaAsO2) conditions, there is a decrease in the CSH and an increase in the primary CS usage to induce antioxidant gene expression. Key oxidative stress response genes (NQO1, HMOX1, PRDX1, and CAT) also show higher CSH compared to the non-stress response genes and that the number of CSs are reduced to impart cellular response to oxidative stresses. Concomitantly, ectopic expression of one of the key antioxidant response gene (NQO1) driven by the primary CS but not from other subsidiary CSs, or reduction in CSH imparts tolerance to cellular oxidative stresses (H2O2, and NaAsO2). Genome-wide CS analysis of stress response genes also shows a similar result. Compromised CSH or CSH-mediated gene control hampers cellular response to oxidative stress. We establish that oxidative stress induces affinity/strength of cleavage complex assembly, increasing the fidelity of cleavage at the primary CS, thereby reducing CSH inducing antioxidant response. Together, our study reports a novel cleavage imprecision- or CSH-mediated anti-oxidant response mechanism that is distinct and operates downstream but in concert with the transcriptional pathway of oxidative stress induction.

Oxidative stress is a pathological condition that contributes to the onset of various diseases. In this way, studying oxidative stress could lead to significant discoveries in the field of therapeutic and preventive medicine. Lipid peroxidation is the most significant event in the oxidative stress process and the gold standard biomarkers for endogenous oxidative damage to lipids are isoprostanes (IsoPs). This project aims to develop a reliable analytical method for the liquid-liquid microextraction technique, parallel artificial liquid membrane extraction (PALME) and LC-MS/MS analysis. PALME allowed to obtain a significant enrichment factor and, at the same time, a good sample purification by removing compounds that cause signal suppression, thereby reducing matrix effect. The chromatographic and mass spectrometric conditions have been fine tuned to improve the sensitivity of the method and therefore obtaining very low LOD and LOQ values. The recovery values obtained for the analytes are slightly above 50 %, except for 6-keto Prostaglandin F1A (24 %). Matrix effects were ≤ -10 %, with LODs ranging between 1 and 5 pg mL-1. The developed method is characterized by high sensitivity and low consumption of organic solvents, according to the principles of Green Analytical Chemistry and enables the determination of basal levels of IsoPs in oral fluid by processing 96 samples simultaneously.

Polysaccharides are valuable macromolecules due to their multiple bioactivities, safety, and a wide range of sources. Recently, a series of polysaccharides with antioxidant activity have been intensively reported. In this review, the latest advances in polysaccharides with antioxidant activity have been reviewed, primarily based on the investigations of polysaccharides regarding advanced extraction methods, roles in oxidative stress-related diseases, intracellular signaling pathways associated with antioxidant responses, activating pathways in the gut, structure-function relationships, and methods to improve antioxidant activity. The summarized information highlighted that much work needs to be conducted, from laboratory to industry, to understand and fully utilize the antioxidant potential of polysaccharides. Finally, future perspectives, including scaling-up of advanced extraction methods, standardizing the protocols for assessing and screening polysaccharides, bridging gaps on the biological mechanisms underlying antioxidant activity, performing clinical trials, and elucidating structure-antioxidant relationships, have been addressed. The information present in this review will be helpful to the scientific community when studying on polysaccharides with antioxidant potential and provides research directions for a better understanding of the polysaccharides and promotes their successful applications in functional foods and nutraceuticals.

Microalgae are emerging as valuable sources of bioactive compounds. This study evaluates hexane extracts from Thalassiosira sp. and Raphidonema sp., and Arthrospira sp., for their bioactive potential. Saturated fatty acids predominated in Arthrospira sp. and Thalassiosira sp. while Raphidonema was rich in polyunsaturated fatty acids. Carotenoids, such as carotenes and xanthophylls, were abundant in Arthrospira sp., while Thalassiosira sp. contained chlorophylls and fucoxanthin derivatives, and Raphidonema sp. showed high levels of chlorophylls and xanthophylls. Antioxidant assays revealed up to 70 % radical scavenging activity, 60 % iron chelation, and up to 67 (μM) ferric-reducing power. Dose-dependent protective effects were observed in Schizosaccharomyces pombe and HepG2 cells, with viability improvements up to 50 %, indicating their potential as antioxidant-rich ingredients for functional foods, promoting health and disease prevention. This study enhances our understanding of Thalassiosira sp. and Raphidonema sp. while underscoring the promising applications of microalgae extracts in functional foods.

Renal Ischemia-Reperfusion Injury (RIRI) often arises due to heightened oxidative stress, rendering it a central focus of research. Sestrin2 plays a pivotal role in regulating oxidative stress; nevertheless, its impact on the renoprotective properties of Eugenol (EU) during RIRI warrants further investigation.

Mice and TCMK-1 cells were categorically assigned into six groups: Sham/Control, Ischemia-Reperfusion (IR)/HR (Hypoxia-Reoxygenation), IR/HR+EU, Sham/Control+Sestrin2-KO, IR/HR+Sestrin2-KO, and IR/HR+EU+Sestrin2-KO. The effects of EU and the involvement of Sestrin2 in RIRI/HR were evaluated using Urea Nitrogen (BUN), Creatinine (Scr), Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), and Malondialdehyde (MDA) assay kits; western blotting; cell viability assays; HE-staining; and Reactive Oxygen Species (ROS) detection.

Following RIRI/HR, a marked deterioration in kidney function and a significant surge in oxidative stress levels were observed. However, EU treatment ameliorated renal injury and inhibited oxidative stress. Additionally, EU upregulated Sestrin2 expression, and the renoprotective effects of EU were reversed upon Sestrin2 knockdown.

The present study posits that EU effectively mitigates RIRI/HRI (Hypoxia-Reoxygenation Injury), and its mechanism of renal protection potentially involves the upregulation of Sestrin2, coupled with the inhibition of oxidative and Endoplasmic Reticulum Stress (ERS).

The "Life's Essential 8" (LE8) is a comprehensive lifestyle assessment tool by the American Heart Association, designed to mitigate cardiovascular disease risk by optimizing lifestyle factors including diet, physical activity, and other health metrics. While individual components of LE8 have been linked to reduced cancer risks, comprehensive studies on LE8 score trajectories over time and their relation to cancer risk are lacking. This study employed the Kailuan cohort, involving 48,330 participants who underwent three health examinations from 2006 to 2010 to determine their LE8 scores. LE8 score trajectories were analyzed using latent mixture modeling, and their association with incident cancer risks was assessed through Cox proportional hazard models, adjusting for confounders such as age, biological sex, and lifestyle behaviors. Three distinct LE8 trajectory patterns were identified: low-stable (21.2%), moderate-stable (49.4%), and elevated-stable (29.4%). Participants with elevated-stable trajectories showed a 21% (HR = 0.79; 95% CI: 0.70-0.90), 27% (HR = 0.73, 95% CI: 0.57-0.92), 51% (HR = 0.49, 95% CI: 0.32-0.77), 31% (HR = 0.69, 95% CI: 0.50-0.97) and 39% (HR = 0.61, 95% CI: 0.39-0.95) reduction in overall, lung, breast, colorectal and liver cancer risk compared to those with low-stable scores. Notably, the protective effect of elevated-stable LE8 scores against breast cancer was pronounced in participants with elevated CRP levels, indicating an interaction between inflammation and LE8 trajectories. Maintaining high and stable LE8 scores significantly associated with reduced cancer risk, underscoring the importance of integrating LE8 into public health and clinical strategies for cancer prevention. Kailuan study, ChiCTR-TNRC-11,001,489. Registered August 24, 2011-Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050 .

Renal fibrosis is a hallmark and the final outcome of chronic kidney disease (CKD). Jingtian Granule (JT), a traditional formula used in the clinical treatment of CKD for many years. However, the mechanism of action of JT against renal interstitial fibrosis remain unknown.

This study aimed to explore the potential effects and mechanisms of JT on adenine - diet - induced CKD in mice.

Renal interstitial fibrosis was induced in mice by adenine - diet and treated with JT. Renal function was assessed by measuring blood urea nitrogen and serum creatinine levels. Masson's staining and type I collagen expression were used to evaluate renal collagen deposition. RNA sequencing was used to analyze the expression levels of mRNA in mouse kidney samples after JT treatment. The levels of glutathione (GSH) and malondialdehyde (MDA) were measured to assess lipid peroxidation in the kidneys. Iron metabolism levels were detected by Prussian blue staining and measurement of iron content. The protein levels of SIRT3, P53, glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) were detected by Western blot. Subsequently, under the premise of SIRT3 knockout, renal function, fibrosis level, iron metabolism level, and lipid peroxidation level were detected, and mitochondrial damage was observed by transmission electron microscope (TEM). In addition, human proximal tubule epithelial cells (HK - 2) were treated with Erastin to induce ferroptosis, followed by exposure to JT. The levels of reactive oxygen species (ROS) were detected.

JT significantly reduced collagen deposition in the kidneys. RNA sequencing identified 20 mRNAs that were differentially expressed in response to JT treatment. Bioinformatics analysis revealed that SIRT3 was a key mRNA regulated by JT. JT activated SIRT3 in fibrotic kidneys to inhibit the acetylation of P53. Under the premise of SIRT3 knockout, JT did not show significant therapeutic effects in inhibiting ferroptosis and fibrosis. In vitro experiments also showed that JT promoted the downregulation of ROS.

SIRT3 is the key ferroptosis - related mRNA regulated by JT. The ability of JT to modulate the SIRT3/P53 signaling pathway may be a viable approach for the treatment of renal interstitial fibrosis.

Mounting evidence suggests that malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) are valuable biomarkers of lipid and nucleic acid oxidation in numerous canine diseases. However, their application in clinical settings is limited due to the absence of reference intervals (RI) and the analytical inconsistencies. Therefore, this study aimed to characterize serum MDA and 8-OHdG concentrations in dogs, to establish assay-specific RI, and to identify biological, haematological and biochemical factors influencing these markers.

A total of 190 clinically healthy dogs were recruited, including pet dogs, working dogs and shelter dogs. Serum MDA concentration was measured by the Thiobarbituric Acid Reactive Substances (TBARS) assay, while 8-OHdG levels were determined by using a competitive ELISA. RI were established by non-parametric methods. Potential associations between oxidative stress (OS) biomarkers and multiple biological, haematological and biochemical factors were assessed using multivariate regression models.

RI for serum MDA (1.85-14.51 µM) and 8-OHdG (0.06-0.75 ng/mL) were established in the reference population (144 and 143 dogs, respectively). The multivariate regression model for MDA revealed a positive association with total cholesterol concentration, and a negative association with monocyte count. 8-OHdG level was positively associated with urea concentration. Notably, both models also revealed a significant association between MDA and 8-OHdG. Biological factors, including the age and size of the animals, did not exert a significant influence on the results.

This is the first study to establish serum RI for MDA and 8-OHdG in a large and diverse canine population. Additionally, the multivariate regression models identified relevant haematological and biochemical, but not biological factors that should be considered when interpreting the results. These findings could significantly enhance the application of MDA and 8-OHdG as biomarkers in clinical settings, and promote further exploration of their value in canine diseases.