This study sought to ascertain if zinc nanoparticles (ZnNPs) could lessen the toxicity of azoxystrobin (AZ). This naturally occurring methoxyacrylate is one of the most often used fungicides in agriculture in male albino rats. Six sets of 60 mature male albino rats were randomly assigned: control (distilled water), Azoxystrobin formulation (AZOF), Azoxystrobin nano-formula (AZON), ZnNPs, AZOF + ZnNPs, and AZON + ZnNPs. Blood and tissues were obtained for further immunohistochemical, pathological, and biochemical examination. The results showed that exposure to AZOF and AZON significantly increased the levels of the oxidative stress indicators glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Additionally, AZOF significantly impacts liver function bioindicators, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. AZOF and AZON induced damage to the liver and kidney by disrupting vascular dilatation and causing hemorrhages, apoptosis, inflammatory lymphocytes, and necrosis. Furthermore, co-administration of ZnNPs with fungicides (AZOF and AZON) can gently enhance the alterations of oxidative stress and liver function bioindicators levels. These findings showed that ZnNPs could help male rats receiving AZ treat their histologically abnormal liver and kidney.

Irisin, a myokine released during exercise, has been shown to exert protective effects against metabolic and inflammatory disorders. Its role in mitigating hepatic damage induced by anabolic-androgenic steroids (AAS) remains largely unexplored. This study was conducted to examine the effects of exercise on irisin level and its capability to prevent hepatotoxicity caused by anabolic androgenic steroids (AAS) in rat model. The fifty-two male rats were divided into four groups: control, AAS treated (15 mg/kg/day S.C/8 W), exercised, and exercised- AAS treated. The following procedures were carried out: liver function tests, serum irisin, tissue inflammatory and oxidative stress markers, macro and micromorphological evaluation, and the examination of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-gamma (PPARγ) and its coactivator-1α (PGC1α) by immunohistochemistry. The liver tissue's expression of nuclear factor kappa B (NF-κB), Toll-like receptor-4 (TLR4), and Nrf2 mRNA was also assessed. After administering AAS to animals, aerobic exercise was found to significantly improve liver function tests, inflammation, and oxidative stress, reduce liver weight, improve morphological and histological changes, and improve the hepatic injury score. Furthermore, there was a notable rise in serum irisin, hepatic PPARγ, PGC1α, and Nrf2 immune-expressions and Nrf2 mRNA expression, while NF-κB and TLR4 mRNA expressions were significantly decreased. In conclusion, the irisin/PGC1α/PPARγ/Nrf2 and Nrf2/NF-κB/TLR4 signaling pathways may be modulated by aerobic exercise, which also reduces the liver's oxidative stress and inflammatory reactions to AAS treatment.

Colchicine (CHC), a poisonous plant alkaloid, has been widely utilized for decades in the treatment of gout, but has a rather low therapeutic index, which causes oxidative stress leading to cognitive impairment, brain damage, apoptosis, and hitopathological alterations in humans and experimental animals. The present investigation evaluated the potential palliative effect of the pumpkin seeds oil (PSO) at a dose of 4 ml/kg b.wt against CHC (0.6 mg/kg b.wt) -induced neurotoxic and neurobehavioral effects in rats. Forty male rats weighing 245-260 g were assigned to four groups. The results displayed that CHC exposure induced neurobehavioral disorders and a remarkable decline in the serotonin and dopamine levels and the immunoexpression of BDNF and GFAP in the brain. Besides, CHC treatment evoked brain oxidative stress, as manifested by depleted antioxidant enzyme activities and elevated malondialdehyde (MDA) and protein carbonyl (PC) levels. Also, CHC triggered brain DNA damage, as indicated by a marked increment in the brain 8-Hydroxyguanosine (8-OHdG) level. However, concurrent treatment with the PSO effectively attenuated the CHC-induced toxic effects as evidenced by a noticeable increase in the serotonin (33 ± 3.05) and dopamine (2.48 ± 0.40) concentrations, and the BDNF and GFAP immunoexpression in the brain. Moreover, PSO mitigated CHC-induced brain oxidative stress and DNA damage as shown by elevated antioxidant enzyme activities (164 ± 3.46 SOD and 7.55 ± 0.43 CAT) and reduced MDA (1.62 ± 0.23), PC (1.35 ± 0.23), and 8-OHdG (3.02 ± 0.33) levels. These results concluded that PSO could serve as a therapeutic strategy to ameliorate the neurotoxic and neurobehavioral impacts of CHC.

Iron oxide nanoparticles (IONPs) are widely used in various fields, particularly in medicine, where they can be directly injected for diagnostic and therapeutic purposes, although they may induce certain types of toxicity. Therefore, the present work aimed to estimate the potential protective role of the oral extract of rosemary (RO)against the toxic effects of injected IONPs on the brain tissues of adult male rats, and to explore the potential underlying mechanisms involved in reversing such toxicity. Thirty adult male albino rats were allocated into five groups: the control, the vehicle (intravenous saline injection once/week), the RO extract group (orally gavaged100mg/kg/day), IONPs (intravenously injected 30 mg/kg once/week), and the combined RO+IONPs (orally gavaged RO extract 1 hrh before intravenous injection of IONPs). IONPs induced neurotoxicity via triggering a cascade of neuro-oxidative stress, neuro-inflammation, and parthanatos-mediated neuronal cell death by increasing MDA, NO, TNF-α levels, PARP-1, AIF, and NF-κB mRNA expression alongside reducing GSH levels. These incidents contributed to neurodegenerative changes, reflected in increased mRNA expression of α-S, β-APP, and TDP-43. Additionally, IONPs induced structural degenerative changes and elevated iron levels in brain tissues reduced occludin expression, and disrupted the BBB. Furthermore, the concurrent oral RO extract alleviated these conditions and repaired BBB by increasing the occludin expression and ameliorating structural changes in brain tissues. Consequently, the current data provide evidence that RO supplementation during IONP administration holds promise to minimize potential health risks, which should be corroborated by translational studies.

The medicinal application of pomegranate peel extract enriched with polyphenols (PPE) as a therapeutic strategy for managing inflammatory bowel diseases (IBD) is still limited. Integrating pomegranate peel extract (PPE) into an effective nanocarrier system could enhance its mechanistic actions, potentially aiding in the remission of colitis. Therefore, this approach aimed to enhance PPE's stability and bioavailability and investigate mitigating impact of pomegranate peel extract-loaded nanoparticles (PPE-NPs) in a colitis model. Colonic injury was induced by 5% dextran sulfate sodium (DSS) and efficacy of disease progression after oral administration of PPE-NPs for 14 days was assessed by evaluating clinical signs severity, antioxidant and inflammatory markers, expressions of endoplasmic reticulum associated genes and histopathological and immunostaining analysis in colonic tissues. Clinical signs and disease activity index were effectively reduced, and the levels of fecal calprotectin were decreased in groups treated with PPE-NPs compared to DSS group. The colitic group showed a significant increase (P < 0.05) in C-reactive protein (CRP) and myeloperoxidase (MPO) and nitric oxide (NO) (35.60, 163.30 and 280 nmol/g tissue respectively) and higher expression (P < 0.05) IL-17, TNF-α, and IL-1β (increased up to 2.99, 4.36 and 4.90 respectively unlike PPE-NPsIII that recorded reduced levels of CRP, MPO and NO (8,96, 78.30 and 123 nmol/g tissue respectively) and much lower (P < 0.05) levels of IL-17, TNF-α, and IL-1β expression (decreased to 1.23, 1.69 and 1.64, respectively). The most improvement of colon damage PPE-NPsIII group was also associated with the reduction MDA level (P < 0.05) (decreased to 21.60 vs 90.65 in DSS non treated group). The highest glutathione peroxidase, superoxide dismutase and catalase activities were noted in PPE-NPsIII received group (42.60, 50.30 and 62.70 U/mg). Notably, prominent free radical scavenging activities were noticed in group received 150 mg/kg of PPE-NPs as supported by higher scavenging of 1,1-diphenyl-2-picrylhydrazyl (9.85 mg/g) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid tested radicals (19.98 mg/g). Balancing between endoplasmic reticulum stressors (ERS), inflammation and autophagy was prominently noted in group treated with 150 mg/kg of PPE-NPs. These findings were supported by subsiding the excessive expression of ERS related genes (CHOP, JUNK, ATF6, BIP, and Elf-2) and immunostaining expression regulation of key markers regulating autophagy (Beclin-2) in this group. The histopathological changes in the colon were less severe in the PPE-NPs received groups (especially at the level of 150 mg/kg) compared to DSS group. Collectively, these findings suggest that the nanoencapsulation of PPE enhances its effectiveness in promoting recovery of colonic tissue damage and achieving remission of colitis.

This study aims to evaluate the anticancer properties of chamomile nano-emulsion (Cha-NE) and α-lactalbumin (α-LA) coated Cha-NE (LA-Cha-NE) against breast tumor through both in vitro and in vivo investigations. Both Cha-NE and LA-Cha-NE exhibited typical semi-spherical forms under Transmission electron microscope (TEM), and displayed surface charges of 46.75 and 28.45 mV with average sizes of 87.46 and 112.75 nm, respectively. In a safe manner, Cha-NE and LA-Cha-NE showed higher selectivity against breast cancer (MDA-MB-231 and MCF7) cells than normal (HSF) cells. Reductions in serum contents of IL1β, TNF-α, IL-4, IL-6, IL-10, ASAT, ALAT, creatinine, urea, triglycerides, and cholesterol, as well as an the administration of LA-Cha-NE, breast tumor incidence dramatically reduced. Thus, improvement in survival rates leads to successful prevention of mammary tumorigenesis as proved by the histopathological and immunohistochemistry findings. However, there was an increase in mammary GSH, GPx, CAT, and SOD activity. Both in vitro and in vivo investigations showed that LA-Cha-NE had a beneficial therapeutic effect, exhibiting more significantly regulated apoptosis and elevated expression of genes that regulate the cell cycle. Thus, this study demonstrated that the chemo-preventive property of LA-Cha-NE may offer a brand-new alternative therapy to cure breast cancer by re-establishing the compromised oxidative stress response, enhancing the immune response, reducing inflammation process, and fortifying the apoptosis pathway.

This study evaluated the potential efficacy of eco-friendly biofabricated zinc oxide nanoparticles (GS-ZnONP) (10 mg/kg b.wt) to reduce the impacts of long-term oral acrylamide (ALD) exposure (20 mg/kg b.wt) on the blood cells, immune components, splenic oxidative status, and expression of CD20, CD3, CD4, CD8, TNF-α, caspase-3, microRNA-181a-5p, and microRNA-125-5p in rats in a 60-day experiment. The study findings revealed that GS-ZnONP significantly corrected the ALD-induced hematological alterations. Additionally, the ALD-induced increase in the serum C3, splenic ROS, CD4, CD8, and MDA and histological alterations were significantly repressed in the ALD + GS-ZnONP-treated rats. Instead, the depleted splenic antioxidants and Zn contents were markedly reestablished in the ALD + GS-ZnONP-treated group. Additionally, a significant upregulation of expression of splenic CD3, CD4, CD8, CD20, TNF-α, and caspase-3, but downregulation of microRNA-181a-5p and microRNA-125-5p was detected in the ALD-exposed group. Yet, the former deviations in the gene expressions were corrected in the ALD + GS-ZnONP-treated rats. Furthermore, GS-ZnONP treatment significantly minimized the increased caspase-3 and TNF-α immunoexpression in the splenic tissues of ALD-exposed rats. Conclusively, the study findings proved the efficacy of GS-ZnONP in rescuing ALD-induced disturbances in blood cell populations, immune function, splenic antioxidant status, and immune-related gene expression.

A total of sixty commercial beef products, represented by minced meat, sausage, kofta, and burger, with fifteen samples per product, were collected randomly from different markets in Assiut city, Egypt. Samples were examined histologically, immunohistochemically and molecularly to investigate tissue composition and species substitution. Polymerase Chain Reaction (PCR) was applied to confirm the beef origin of different marketed beef products and determine if there are any adulteration and/or contamination with rodents and canine species. The histological investigation finds significant differences in skeletal muscle content, with the highest proportion in minced meat, whereas the lowest detected in kofta. Several animal tissues were detected, including adipose tissue, collagen, cartilage, and bone, where kofta showed the highest levels. We also detected plant tissues, predominantly found in burger samples. Expression Bcl2 indicated the maximum intensity in sausage, while burger showed the lowest expression. PCR results revealed that 89.13% were pure beef products, 10.87% were with rat meat contamination, and 100% of examined samples were negative for canine species. These results highlight the efficacy of histology, Bcl2 immunohistochemistry and PCR in assessing meat quality and distinguishing adulteration.

This study investigated the potential neuroprotective role of Moringa oleifera leaf powder (MOLP) dietary supplementation on imidacloprid (IMD)-induced neurobehavioral disturbances, oxidative stress, and apoptosis in broiler chicken brains. In a 6 week trial, 150 day-old commercial meat-type Ross 308 broiler chicks were randomly divided into five equal groups of 30 chicks each. The control and MOLP groups were fed a basal diet and a basal containing diet 25 g MOLP/kg, respectively, for 6 weeks. The IMD group was fed a basal diet for 2 weeks, followed by a basal diet containing 50 mg IMD/kg for 4 weeks. The IMD + MOLP combined group was fed a basal diet for 2 weeks, followed by a basal diet containing both IMD and MOLP for 4 weeks. The MOLP/IMD + MOLP prophylactic group was fed a MOLP-fortified diet for 2 weeks, followed by a basal diet containing both IMD and MOP for 4 weeks. MOLP supplementation effectively reversed IMD-induced reductions in feeding behavior and locomotor activity while decreasing crouching behavior and fearfulness. Dietary MOLP significantly restored the IMD-induced depletion of brain antioxidants while lessening lipid peroxidation, pathological alterations, and Caspase-3 immunoexpression. Yet, the brain AChE content did not change significantly among the experimental groups. However, dietary MOLP significantly reversed IMD-induced apoptotic-related genes (P21 and Caspase-3) upregulation and neuronal development-related genes (BDNF, GLP-1, PGC-1α, and PPARA) downregulation. Notably, the MOLP/IMD + MOLP prophylactic group showed more enhanced neuroprotection than the IMD + MOLP combined group. In conclusion, our study highlighted the IMD neurotoxic effects in broiler chickens and showed, for the first time, the neuroprotective potential of MOLP as a dietary supplement against IMD exposure.

We aimed to investigate TLR-4 receptor activity in the development of endometriosis and the effect of trastuzumab in experimentally induced endometriotic tissue via TLR-4 in this study. Twenty-eight female Wistar-Albino rats were divided into four groups: Group 1 (Control Group), Group 2 (Endometriosis Group), Group 3 (Endometriosis + Trastuzumab Group), and Group 4 (Trastuzumab Group). All animal tissue samples were collected. Histopathological, immunohistochemical, and biochemical analyses were performed. In histopathological analysis, there was a significant difference between Group 2 and other groups in terms of connective tissue edema, inflammation, hemorrhage, epithelial damage, and mast cell density. In immunohistochemical analysis with TLR-4, Group 2 exhibited strong staining. In biochemical analysis, it was found that there was a highly significant difference between Group 2 and Group 1 considering the Malondialdehyde (MDA) levels in plasma samples. There was no significant difference in terms of the MDA levels among other groups. Considering the glutathione levels in the plasma samples, it was found that there was a highly significant difference between Group 2 and Groups 3 and 4. Trastuzumab may play a role in the treatment of histopathological damage and fibrosis in experimentally induced endometriotic implants by showing anti-inflammatory and antiproliferative activity.

Tubulointerstitial fibrosis (TIF) is present with chronic kidney disease (CKD). Vinpocetine (Vinpo) is used for treating cerebrovascular deficits, exhibiting some kidney-beneficial effects; however, its role in TIF is uncertain. So, the aim of this study was to investigate its potential impact on adenine-induced fibrotic CKD and explore the underlying mechanistic aspects. Eighteen male Wistar rats were categorized into three groups (n = 6 each). Group I was kept as controls and given saline; group II received adenine (300 mg/kg, twice weekly, i.p.) for induction of the CKD model; and group III was administered Vinpo (20 mg/kg/d, orally) concurrently with adenine. All treatments were administered for 4 weeks. Vinpo revealed an improvement in renal function and an alleviation of inflammation triggered by adenine via diminishing serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels. Further, Vinpo repressed the epithelial-mesenchymal transition (EMT) with preserved E-cadherin mRNA expression and lowered gene and immune expression of fibronectin and vimentin, respectively, besides attenuating the elevated G2/M arrest-related molecules (renal Ki67 protein contents and p21 gene expression). Renal pathological alterations caused by adenine were attenuated upon Vinpo administration. Interestingly, Vinpo suppressed abnormal renal β-catenin immunoreactivity, Snail 1, and MMP-7 gene expression while simultaneously restored Klotho protein expression by downregulating DNA methyltransferase 1 enzyme (DNMT1) protein expression in the kidney. These data indicated that Vinpo effectively mitigated EMT and G2/M arrest-induced renal fibrosis in adenine-induced CKD rats by targeting DNMT1-associated Klotho suppression, subsequently inhibiting β-catenin and its fibrotic downstream genes.

Exposure to organophosphorus nerve agents irreversibly inhibits acetylcholinesterase and may lead to cholinergic crisis and seizures. Although benzodiazepines are the standard of care after nerve agent-induced status epilepticus, when treatment is delayed for up to 30 min or more, refractory status epilepticus can develop. Adult male rodents are often utilized for evaluation of therapeutic efficacy against nerve agent exposure. However, there may be age and sex differences in toxicity and in therapeutic response. We previously reported that juvenile rats are less susceptible to the lethal effects of soman compared to adults, while pups are the most susceptible. Here, we report on age and sex differences in delayed midazolam treatment efficacy on survival, seizures and brain pathology. Male and female pups, juvenile and adult rats were exposed to an equitoxic dose of soman and treated with atropine sulfate and the oxime asoxime chloride (HI-6 dimethanesulphonate) 1 min after exposure and with midazolam 40 min after seizure onset, determined by EEG in juvenile and adult rats, and by behavior in pups. Survival, seizure data, and spontaneous recurrent seizures were evaluated. Brains were processed to assess neurodegeneration, neuroinflammation, and blood brain barrier (BBB) integrity. Juvenile and adult rats exposed to soman and treated with midazolam had BBB disruption, epileptogenesis, neurodegeneration, microglial activation, and astrogliosis; adult rats had poorer outcomes. Pups and juvenile rats exposed to soman had poor survival prior to midazolam treatment but most survived once treated; overall, neurodegeneration or disrupted BBB integrity was not detected in midazolam-treated pups. We found that age is a determinant factor in soman-induced toxicity and response to standard medical countermeasures. In addition, we observed sex differences in response to soman in juveniles and males with respect to body weight growth curves and in neuronal loss in juveniles and adults. Adjunct therapies to midazolam are warranted and it is important to evaluate both age and sex as factors in therapeutic response.

Trichinellosis is a severe parasitic disease transmitted by food, specifically caused by Trichinella spiralis, which exhibits great clinical importance worldwide. Albendazole (ABZ) is the main clinical treatment for trichinellosis but has some adverse effects and drug resistance. Sea cucumber Holothuria polii is an essential source of beneficial therapeutic metabolites. Hence, the purpose of the present study was to explore the potential therapeutic effectiveness of H. polii extract (HPE) during the intestinal phase of trichinellosis and the possibility of using it as a supplement to ABZ. For this purpose, mice were divided into a control group and four T. spiralis-infected groups: infected untreated, infected and ABZ-treated, infected and HPE-treated, and infected and combined therapy-treated groups. The treatment with the combined therapy decreased parasitic load by 96.76%, caused deleterious effects on the adult worm cuticle, improved jejunum histological architecture, diminished intestinal inflammatory cytokines, and decreased oxidative damage compared with the infected untreated group and ABZ-treated group. The ameliorating effect of HPE could be due to its total antioxidant capacity content and the presence of natural anti-inflammatory and antioxidant agents like saponins, phenolics, alkaloids, and flavonoids. In conclusion, HPE has a multifaceted, effective impact on trichinellosis and can be considered an ABZ-promising complementary treatment.

Rabies virus (RABV) is a lethal and neglected zoonosis responsible for over 60,000 deaths annually caused by the neurotropic virus Lyssavirus rabies. Although rabies is well-known for its severe nervous system impairment, little is known regarding the specific alterations caused in extraneural organs. Studies suggest an essential involvement of RABV in the kidneys. However, the extent of the pathological damage caused by RABV in this organ remains to be understood. This study describes the histopathological alterations and RABV antigen expression in the kidneys and urinary bladder. Viral immunostaining was observed, suggesting that RABV can successfully infect these tissues. In addition, the main alterations found in the kidneys were edema in the convoluted tubules and in the glomerulus, interstitial inflammation, atrophy of the glomerular tuft, a decrease in Bowman's capsule and Bowman's space, and the accumulation of glycogen in the tubules, which may indicate the effects of inflammation caused by RABV. Therefore, our results showed the importance of understanding the effects of histopathological alterations induced by RABV and the need for more studies concerning the inflammatory action of the virus during the infection.

Background: Aging is a complex biological process characterized by the accumulation of molecular and cellular damage over time, often driven by oxidative stress. This oxidative stress is particularly detrimental to the testes, where it causes degeneration, reduced testosterone levels, and compromised fertility. D-galactose (D-gal) is commonly used to model aging as it induces oxidative stress, mimicking age-related cellular and molecular damage. Testicular aging is of significant concern due to its implications for reproductive health and hormonal balance. This research examines the protection by thymoquinone (TQ) or thymoquinone-loaded chitosan nanoparticles (NCPs) against D-galactose (D-gal)-induced aging in rat testes, focusing on biochemical, histological, and molecular changes. Aging, which is driven largely by oxidative stress, leads to significant testicular degeneration, reducing fertility. D-gal is widely used to model aging due to its ability to induce oxidative stress and mimic age-related damage. TQ, a bioactive ingredient of Nigella sativa, has earned a reputation for its anti-inflammatory, anti-apoptotic, and antioxidant characteristics, but its therapeutic application is limited by its poor bioavailability. Methods: Thymoquinone was loaded into chitosan nanoparticles (NCPs) to enhance its efficacy, and this was hypothesized to improve its stability and bioavailability. Four groups of male Wistar rats participated in the study: one for the control, one for D-gal, one for D-gal + TQ, and the last one for D-gal + NCP. Results: The results exhibited that D-gal substantially increased oxidative injury, reduced testosterone levels, and caused testicular damage. Treatment with TQ and NCPs significantly reduced oxidative stress, improved antioxidant enzyme levels, and restored testosterone levels, with NCPs showing a stronger protective effect than TQ alone. A histological analysis confirmed that NCPs better preserved testicular structure and function. Additionally, the NCP treatment upregulated the expression of key genes of oxidative stress resistance, mitochondrial function, and reproductive health, including SIRT1, FOXO3a, and TERT. Conclusions: The findings suggest that NCPs offer enhanced protection against aging-related testicular damage compared with TQ alone, which is likely due to the improved bioavailability and stability provided by the nanoparticle delivery system. This research emphasizes the potential of NCPs as a more effective therapeutic strategy for mitigating oxidative stress and age-related reproductive dysfunction. Future research should further explore the mechanisms underlying these protective effects.

Conflict reports exist on the impact of pyrethroid insecticides on immune function and the probable underlying mechanisms.

This study evaluated the effect of an extensively used pyrethroid insecticide, fenpropathrin (FTN) (15 mg/kg b.wt), on the innate and humoral immune components, blood cells, splenic oxidative status, and mRNA expression of CD3, CD20, CD56, CD8, CD4, IL-6, TNF-α, and Caspase3 in a 60-day trial in rats. Besides, the possible defensive effect of curcumin-loaded chitosan nanoparticle (CML-CNP) (50 mg/kg b.wt) was evaluated.

FTN exposure resulted in hypochromic normocytic anemia, thrombocytosis, leukocytosis, and lymphopenia. Besides, a significant reduction in IgG, not IgM, but increased C3 serum levels was evident in the FTN-exposed rats. Moreover, their splenic tissues displayed a substantial increase in the ROS, MDA, IL-6, and IL-1β content, altered splenic histology, and reduced GPX, GSH, and GSH/GSSG. Furthermore, a substantial upregulation of mRNA expression of splenic CD20, CD56, CD8, CD4, CD3, IL-6, and TNF-α, but downregulation of CD8 was detected in FTN-exposed rats. FTN exposure significantly upregulated splenic Caspase-3 and increased its immunohistochemical expression, along with elevated TNF-α immunoexpression. However, the alterations in immune function, splenic antioxidant status, blood cell populations, and immune-related gene expression were notably restored in the FTN + CML-CNP-treated group.

The findings of this study highlighted the immunosuppressive effects of FTN and suggested the involvement of many CD cell markers as a potential underlying mechanism. Additionally, the results demonstrated the effectiveness of CML-CNP in mitigating pollutant-induced immune disorders.

The study aims to investigate whether selenium (Se) has a protective role against testicular toxicity induced by 4-nonylphenol (4-NP) in rats and reduces oxidative damage. For this purpose, 30 adult male Sprague-Dawley rats (250-300 g/90 days old) were divided into five equal groups: control, sham control, Se, 4-NP, and 4-NP + Se. The trial lasted 48 days, with 4-NP administered at 125 mg/kg/day and Se at 0.5 mg/kg/day. The general microscopic examination of the testicular tissue involved measuring the diameters of seminiferous tubules, epithelial heights, and the density of stage XIV tubules in sections stained with the triple staining method. Caspase 3 and CX43 expressions were observed immunohistochemically, and the numbers of live-dead and normal-abnormal spermatozoa were recorded. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in blood serum and testicular tissue. At the end of the study, testicular toxicity due to 4-NP was demonstrated cytologically, histologically, histometrically, biochemically, and immunohistochemically. Se showed a positive effect against this toxicity, as evidenced by higher stage XIV tubule density in the 4-NP + Se group, lower caspase 3 levels compared to the 4-NP group, decreased MDA levels, increased SOD levels in serum and testicular tissue, and a higher count of live and normal spermatozoa. When used alone, Se may cause metabolic adverse effects, such as decreased live weight gain, reduced tubule diameter and epithelial height, and increased caspase 3 expression, depending on the dose and duration of use.

Liposarcoma (LPS) is the most prevalent soft tissue sarcoma. The most common biological subtypes are well-differentiated (WDLPS), a low-grade disease that can evolve to high-grade dedifferentiated LPS (DDLPS), with increased rates of recurrence and metastasis and low response rates to chemotherapy and targeted therapies. Preclinical testing of immunotherapeutics for LPS has been held back by the lack of an immunocompetent mouse model. Here, we present a spontaneous immunocompetent LPS mouse model, ACPP, with targeted deletion of Trp53 and Pten in adipocytes to mimic signaling alterations observed in human LPS. Similar to human LPS, tumors arising in ACPP mice produce WDLPS and DDLPS, along with tumors that exhibit both WD and DD components. Murine and human DDLPS tumors possess transcriptional similarities, including increased expression of oncogenes Cdk4 and Hmga2 and reduced expression of the tumor suppressor Cebpa; further, both mouse and human DDLPS exhibit either high or low T cell infiltration. Syngeneic cell lines derived from spontaneous ACPP DDLPS reliably produce tumors following orthotopic injection, each with distinct growth patterns, aggressiveness and tumor infiltrating lymphocyte profiles. These models provide much needed tools to understand the complex immunobiology of LPS and greatly accelerate the pace of preclinical studies to uncover new therapies for patients with this aggressive malignancy.

This study was executed to mitigate imiquimod (IMQ)-side effects and promote its anticancer potential against skin cancer via encapsulation in hyaluronic acid-coated lipid nanocapsules (HA-LNCs) for targeted topical delivery. The LNCs were prepared using the phase inversion technique. Optimized LNCs formulation was gained following 22 factorial design experiment to adjust the IMQ and CTAB concentrations. The two variables were found to significantly influence the dependent responses. The encapsulation efficiency of IMQ exceeded 97 %. HA coating provided a sustained release of IMQ from LNCs, with 63.81 ± 2.45 % of IMQ released after 24 h. Moreover, the ex-vivo human skin permeation study showed that 7.9-fold more IMQ was localized in all skin layers than that permeated. In vitro anticancer activity indicated that IMQ-HA-LNCs had higher cytotoxicity (IC50 = 22.39 μg/mL) compared to free IMQ (IC50 = 97.94 μg/mL). Further, in vivo studies revealed that encapsulation of IMQ in HA-LNCs enhanced its immunostimulatory potential and promoted its anti-tumor activity in competing skin cancer even in low doses compared to the untreated group and group treated with a brand product with no topical or systemic toxicity. The present study suggested that HA-LNCs with their mixed polymeric/lipophilic nature epitomize a promising strategy for safe topical delivery of poorly water-soluble candidates.

Immunohistochemistry (IHC) is crucial for determining cancer treatments. We previously developed a rapid IHC method and have now developed a fully automated rapid IHC stainer (R-Auto). This study aimed to evaluate the clinical reliability of the R-Auto protocol for staining estrogen receptors (ERs) in breast cancer specimens and evaluate the staining performance.

Between January 2015 and June 2020, 188 surgical specimens collected from breast cancer patients treated at our hospital were evaluated via ER staining using R-Auto, conventional manual IHC, and a commercial autostainer. The specimens were scored using Allred scores, after which the staining results were compared between R-Auto and conventional IHC or the commercial autostainer. Weighted kappa coefficients and AC1 statistics were used to assess the agreement between the methods.

The AC1 statistic for comparison between R-Auto and conventional IHC was 0.9490 (0.9139-0.9841), with a 95.7% agreement rate, and that for comparison between R-Auto and the commercial autostainer was 0.9095 (0.8620-0.9570), with a 92.6% agreement. There was, thus, substantial agreement between R-Auto and both conventional IHC and the commercial autostainer. However, R-Auto shortened the time required for IHC from 209 min with conventional IHC to 121 min.

R-Auto enables a good staining performance in a shorter time with less effort.

Atorvastatin (ATOR) acts on certain antitumor pathways; the consequences of chemotherapies continue to be a major concern, notwithstanding the increased efficacy provided by contemporary therapies. This study investigated the synergistic effects and underlying mechanisms of different treatment protocols using ATOR on the THP-1 cell line and on lung cancer in mice. For the in vitro study, an MTT assay was performed, and then different combinations against the THP-1 cell line were used as follows: non-treated cells, THP-1/ATOR IC50, THP-1/cytarabine (CYT) IC50, THP-1/doxorubicin (DOX) IC50, THP-1/DOX/CYT, THP-1/ATOR/CYT, THP-1/ATOR/DOX, and THP-1/ATOR/CYT/DOX. For the in vivo study, CD-1 male mice were used; G1 was the normal control. Gs2-5 were administered with urethane (Ure) and butylated hydroxytoluene (BHT). G2 was the positive control. G3 was treated with ATOR (20 mg/kg). G4 was treated with Bevacizumab (Bev) (5 mg/kg). G5 was co-treated with ATOR/Bev. Histopathological and immunohistochemical investigations, flow cytometry and molecular analysis of PI3K, Akt, and mTOR genes were performed after different treatment protocols. The results showed that different combinatorial treatment settings of ATOR in vitro increase the apoptotic-inducing capacity and cell cycle arrest. Co-treatment with ATOR and Bev led to a significant decrease in S-phase and G2/M percentages. Furthermore, in vivo co-treatment with ATOR/Bev decreased tumor incidence and size with a significant reduction of the immunohistochemical PCNA (LI%) in lung parenchyma, targeting PI3K/Akt/mTOR, and VEGF-A signaling pathways. Co-treatment with ATOR and chemotherapies led to cell cycle arrest, modulation of the PI3K/Akt/mTOR, and VEGF-A signaling pathways in tumor cells.

Necroptosis is a regulated form of cell death implicated in several pathological conditions, including viral infections. In this study, we investigated the expression and correlation of necroptosis markers MLKL, RIP1 and RIP3 in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). The liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases underwent histopathological analysis, followed by tissue immunostaining with the immunohistochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular zone (Z3), midzonal zone (Z2), periportal zone and portal tract (PT) of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. A quantitative analysis revealed a significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PTs) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. A Pearson correlation analysis demonstrated significant correlations among necroptosis markers, which indicates their coordinated regulation during YF-induced liver injury.

The main objectives of this study were to investigate surfactant apoprotein expression (SP) and to detect Brucella sp. antigens in the lungs of aborted bovine fetuses and neonatal calves delivered weak. The Avidin-Biotin-Peroxidase Complex (ABC) and the indirect immunofluorescence (IF) techniques were applied, using antibodies to the lung surfactant apoproteins (SP-A, SP-B, SP-C) and Brucella sp. antigens. Hyperplasia of type II cells was also assessed by evaluating Thyroid Transcription Factor-1 (TTF-1), Proliferating Cell Nuclear Antigen (PCNA), and Cytokeratin Pan Type I/II (CK-P) markers. The study materials were the lungs of 46 aborted bovine fetuses and 20 neonatal calves delivered weak. Brucella sp.-positive fetal lungs displayed bronchopneumonia in 24 cases. The lungs of the weak-delivered neonates which were positive for Brucella sp. also showed pneumonia. Bacterial culture detected positivity in 11 of 46 fetuses and two neonates. IHC for Brucella sp. antigens found positivity in 22 of 46 fetuses and four neonates. Thus, our research revealed that the IHC technique using anti-Brucella sp. antibodies was useful for detecting Brucella sp. in autolytic and culture-negative fetuses. The study also found that surfactant synthesis begins close to the 7th month of gestation in bovine fetuses. Immunolabeling to SPs occurred in the cytoplasm of both type II and Clara cells, along with SP-C only in type II pneumocytes. The IF yielded dense labeling for Brucella sp. antigens, SP-B, and CK-P, respectively, in the phagocytic cells and epithelium of the airways. Also, pneumonia in newborn calves indicates an intrauterine infection by Brucella sp.

The current study evaluated the influence of the treatment with tea tree oil and cefepime on morpho- genetic, histo-immunohistochemical, and biochemical assessments in rats experimentally challenged with Escherichia coli ATCC 4157™. Thirty adult male rats were divided into control, E. coli infected positive group (1×108CFU/I/P/once), E. coli with cefepime-supplemented group (45 mg/kg bw/I/M/day), E. coli with tea tree oil treated group (1.5 ml/per os/day), and the E. coli-challenged group that received a combination of tea tree oil and cefepime. E. coli infection induced morphological changes in color and texture of both liver and kidney. The transcription levels of the PHLPP2 and Nrf2 genes were noticeably lowered in all treated groups related to the E. coli group. Regarding the TLR4 expression, it was clearly up-regulated in the E. coli group in comparison to other groups, while CD14 gene decreased clearly in all treated groups compared to the positive group. The findings revealed that RBC, HGB, and PCV were clearly higher in the positive group compared to all treated groups. AST, ALT, and ALP, total bilirubin and its fractions, urea, and creatinine maximized in the positive group and decreased by the treatment, especially in the E+CF+oil treated group. Regarding the redox balance, MDA levels of MDA were notably reduced in the E+CF+oil treated group compared to the positive and the other treated groups. GSH, SOD, and GPX were significantly induced in the E. coil-treated group and decreased significantly with treatment. Overall, cefepime is highly safe especially when dually supplied with tea tree oil for mitigating E. coli adverse impact.

Little is known about the effects of acrylamide (AMD) on the stomach. So, this study evaluated the effect of oral AMD exposure (20 mg/kg b.wt) on oxidative status, apoptotic, and inflammatory reactions in rat's stomach for 60 days. To explore novel targets of AMD toxicity, a more detailed molecular and immune-expression study was performed. Besides, the possible protective effect of green synthesized zinc oxide nanoparticles (G-ZNP) (10 mg/kg b.wt) was explored. The results revealed that AMD significantly provoked oxidative and lipid peroxidative damage of the stomach in terms of increased ROS and MDA but reduced SOD, CAT, GSH, and GSH/GSSG. Additionally, the stomachs of AMD-exposed rats showed a significant increment of PGE2 but reduced NO. Histopathologically, AMD induced a significant increase in PAS stain and the immunoexpression of iNOS and NF-κB in the glandular stomach. A significant upregulation of CART, VACHT, EGFR, caspase-3, NOS-1, and miR-27a-5p was evident in the stomach of the AMD group. Yet, G-ZNP oral dosing significantly rescued the AMD-induced oxidative damage, apoptotic reaction, inflammatory effect, and altered miR-27a-5p and gene expressions in the stomach. Conclusively, these findings demonstrated the efficacy of G-ZNP in protecting against the harmful impacts of acrylamide on stomach tissues.

Metabolic syndrome (MetS) is a prevalent public health problem. Uric acid (UA) is increased by MetS. We investigated whether administration of UA and 10% fructose (F) would accelerate MetS formation and we also determined the effects of irisin and exercise. We used seven groups of rats. Group 1 (control); group 2 (sham); group 3 (10% F); group 4 (1% UA); group 5 (2% UA); group 6 (10% F + 1% UA); and Group 7, (10% F + 2% UA). After induction of MetS (groups 3 -7), Group 3 was divided into three subgroups: 3A, no further treatment; 3B, irisin treatment; 3C, irisin treatment + exercise. Group 4, 1% UA, which was divided into three subgroups: 4A, no further treatment; 4B, irisin treatment; 4C, Irisin treatment + exercise. Group 5, 2% UA, which was divided into three subgroups: 5A, no further treatment; 5B, irisin treatment; 5C, irisin treatment + exercise. Group 6, 10% F + 1% UA, which was divided into three subgroups: 6A, no further treatment; 6B, irisin treatment; 6C, irisin treatment + exercise. Group 7, 10% F + 2% UA, which was divided into three subgroups: 7A, no further treatment; 7B, irisin treatment; 7C, irisin treatment + exercise., İrisin was administered 10 ng/kg irisin intraperitoneally on Monday, Wednesday, Friday, Sunday each week for 1 month. The exercise animals (in addition to irisin treatment) also were run on a treadmill for 45 min on Monday, Wednesday, Friday, Sunday each week for 1 month. The rats were sacrificed and samples of liver, heart, kidney, pancreas, skeletal muscles and blood were obtained. The amounts of adropin (ADR) and betatrophin in the tissue supernatant and blood were measured using an ELISA method. Immunohistochemistry was used to detect ADR and betatrophin expression in situ in tissue samples. The duration of these experiments varied from 3 and 10 weeks. The order of development of MetS was: group 7, 3 weeks; group 6, 4 weeks; group 5, 6 weeks; group 4, 7 weeks; group 3, 10 weeks. Kidney, liver, heart, pancreas and skeletal muscle tissues are sources of adropin and betatrophin. In these tissues and in the circulation, adropin was decreased significantly, while betatrophin was increased significantly due to MetS; irisin + exercise reversed this situation. We found that the best method for creating a MetS model was F + UA2 supplementation. Our method is rapid and simple. Irisin + exercise was best for preventing MetS.

Human epidermal growth factor receptor 2 (HER2)-low has emerged as a potential new entity in breast cancer (BC). Data on this subset are limited, and prognostic results are controversial, evidencing the need of further data in a BC real-world cohort.

Patients with HER2-negative stage I-III BC diagnosed between 2006 and 2016 were retrospectively reviewed in a single cohort from the Catalan Institute of Oncology Badalona. Demographics and clinicopathological characteristics were examined via medical charts/electronic health records. We aim to describe and compare HER2-0/HER2-low populations through Chi-square or Fisher test, and explore its prognostic impact using Kaplan-Meier curves and Cox regression models.

From a cohort of 1755 BC patients, 1401 invasive HER2-negative, stage I-III cases were evaluated. 87% were hormone receptor (HR)-positive versus 13% triple negative (TNBC). Overall, 43% were HER2-0 and 57% HER2-low (61% immunohistochemistry (IHC) 1+ and 39% IHC 2+). Comparing HER2-low versus HER2-0, HER2-low showed higher proportion of estrogen receptor (ER)-positive (91.6% vs 79.9%, p ⩽ 0.001) and progesterone receptor (PR)-positive (79.8% vs 68.9%, p ⩽ 0.001) cases. HER2-0 exhibited higher proportion of TNBC (20.1% vs 8.4%, p = 0.001), grade III tumors (28.8% vs 23.5%, p = 0.039), and higher Ki67 median value (26.47% vs 23.88%, p = 0.041). HER2-low was associated with longer time to distant recurrence (TTDR) compared to HER2-0 (67.8 vs 54.1 months; p = 0.015) and better BC-related survival (19.2 vs 16.3 years; p = 0.033). In the multivariable analysis, HER2-low was not an independent prognostic factor for TTDR and BC-related survival. ER expression showed a strong association with longer TTDR (Hazard Ratio: 0.425, p ⩽ 0.001) and improved BC-related survival (Hazard Ratio: 0.380, p ⩽ 0.001). PR expression was also associated with longer TTDR (Hazard Ratio: 0.496, p ⩽ 0.001), and improved BC-related survival (Hazard Ratio: 0.488, p ⩽ 0.001). Histological grade III was significantly associated with shorter TTDR (Hazard Ratio: 1.737, p = 0.002). Positive nodal status was the strongest factor correlated with worse BC-related survival (Hazard Ratio: 2.747, p ⩽ 0.001).

HER2-low was significantly associated with HR-positive disease, whereas HER2-0 group had higher incidence of TNBC, histological grade III and higher Ki67%. Although HER2-low group was associated with longer TTDR and improved BC-related survival, these findings could be explained by the greater proportion of favorable prognostic features in this subgroup compared to HER2-0.

Dermatophytosis is a very common superficial mycosis, but there are few studies about the human immune response to dermatophytes. We aim to analyze the in situ expression of TNF-α and IL-10 in human dermatophytosis. Expression of TNF-α and IL-10 were evaluated in skin samples from 10 patients with dermatophytosis and 12 healthy subjects using an immunohistochemistry assay. TNF-α and IL-10 were significantly elevated in lesions from patients with dermatophytosis compared to healthy controls. These data illustrate the balance of pro- and anti-inflammatory cytokines suggesting Trichophyton rubrum infection could control the local immune response.

We genetically manipulated HaCaT cells, a spontaneously immortalised normal keratinocyte cell line, to stably express two different coloured luciferase reporter genes, driven by interleukin 8 (IL-8) and ubiquitin-C (UBC) promoters, respectively. Subsequently, we generated a three-dimensional (3D) skin-like in vitro composite (SLIC) utilising these cells, with the objective of monitoring bioluminescence emitted from the SLIC. This SLIC was generated on non-woven silica fibre membranes in differentiation medium. Immunohistochemical analyses of skin differentiation markers in the SLIC revealed the expression of keratins 2 and 10, filaggrin, and involucrin, indicating mature skin characteristics. This engineered SLIC was employed for real-time bioluminescence monitoring, allowing the assessment of time- and dose-dependent responses to UV stress, as well as to hydrophilic and hydrophobic chemical loads. Notably, evaluation of responses to hydrophobic substances has been challenging with conventional 2D cell culture methods, suggesting the need for a new approach, which this technology could address. Our observations suggest that engineered SLIC with constitutively expressing reporters driven by selected promoters which are tailored to specific objectives, significantly facilitates assays exploring the physiological functions of skin cells based on genetic response mechanisms. It also highlights new avenues for evaluating the physiological impacts of various compounds designed for topical application to human skin.

Nicotine, a pervasive global environmental pollutant, is released throughout every phase of the tobacco's life cycle. This study examined the probable ameliorative role of Chlorella vulgaris (ChV) extract against nicotine (NIC)-induced hepatic injury in Ehrlich ascites carcinoma (EAC) bearing female Swiss mice. Sixty female Swiss mice were assigned to four equal groups orally gavaged 2% saccharin 0.2 mL/mouse (control group), orally intubated 100 mg ChV /kg (ChV group), orally intubated 100 µg/mL NIC in 2% saccharin (NIC group), and orally intubated NIC + ChV as in group 3 and 2 (NIC+ChV group). The dosing was daily for 4 weeks. Mice from all experimental groups were then inoculated intraperitoneally with viable tumor cells 2.5 × 106 (0.2 mL/mouse) in the fourth week, and the treatments were extended for another 2 weeks. The results have shown that NIC exposure significantly altered the serum levels of liver function indices, lipid profile, LDH, and ALP in the NIC-exposed group. NIC administration significantly increased hepatic inflammation, lipid peroxidation, and DNA damage-related biomarkers but reduced antioxidant enzyme activities. NIC exposure downregulated SOD1, SOD2, CAT, GPX1, and GPX2 but upregulated NF-κB hepatic gene expression. Notably, the presence of the EAC cells outside the liver was common in all mice groups. Liver tissue of the NIC-exposed group showed multifocal expansion of hepatic sinusoids by neoplastic cells. However, with no evidence of considerable infiltration of EAC cells inside the sinusoids or in periportal areas in the NIC + ChV groups. NIC significantly altered caspase-3, Bax, and BcL2 hepatic immune expression. Interestingly, ChV administration significantly mitigates NIC-induced alterations in hepatic function indices, lipid profile, and the mRNA expression of antioxidant and NF-κB genes and regulates the caspase-3, Bax, and BcL2 immunostaining. Finally, the in vivo protective outcomes of ChV against NIC-induced hepatic injury combined with EAC in female Swiss mice could suggest their helpful role for cancer patients who are directly or indirectly exposed to NIC daily.

Vincristine (VCR), a vinca alkaloid with anti-tumor and anti-oxidant properties, is acclaimed to possess cardioprotective action. However, the molecular mechanism underlying this protective effect remains unknown. This study investigated the effects of VCR on isoprenaline (ISO), a beta-adrenergic receptor agonist, induced cardiac hypertrophy in male Wistar rats. Animals were pre-treated with ISO (1 mg/kg) intraperitoneally for 14 days before VCR (25 μg/kg) intraperitoneal injection from days 1 to 28. Thereafter, mechanical, and electrical activities of the hearts of the rats were measured using a non-invasive blood pressure monitor and an electrocardiograph, respectively. After which, the heart was homogenized, and supernatants were assayed for contractile proteins: endothelin-1, cardiac troponin-1, angiotensin-II, and creatine kinase-MB, with markers of oxidative/nitrergic stress (SOD, CAT, MDA, GSH, and NO), inflammation (TNF-a and IL-6, NF-kB), and caspase-3 indicative of VCR reduced elevated blood pressure and reversed the abnormal electrocardiogram. ISO-induced increased endothelin-1, cardiac troponin-1, angiotensin-II, and creatine phosphokinase-MB, which were reversed by VCR. ISO also increased TNF-α, IL-6, NF-kB expression with increased caspase-3-mediated apoptosis in the heart. However, VCR reduced ISO-induced inflammation and apoptosis, with improved endogenous antioxidant agents (GSH, SOD, CAT) relative to ISO controls. Moreso, VCR, protected against ISO-induced histoarchitectural degeneration of cardiac myofibre. The result of this study revealed that VCR treatment significantly reverses ISO-induced cardiac hypertrophic phenotypes, via mechanisms connected to improved levels of proteins involved in excitation-contraction, and suppression of oxido-inflammatory and apoptotic pathways.

Type 2 diabetes is one of the most prevalent chronic diseases worldwide, significantly impacting patients' quality of life. Current treatment options like metformin (MET) effectively counteract hyperglycemia but fail to alleviate diabetes-associated complications such as retinopathy, neuropathy, nephropathy, hepatopathy, and cardiovascular diseases.

To propose the supplementation of cholecalciferol (CHO) and taurine (TAU) to enhance MET efficacy in controlling diabetes while minimizing the risk of associated complications.

The study involved sixty rats, including ten non-diabetic control rats and fifty experimental rats with type 2 diabetes induced by streptozotocin. The experimental rats were further subdivided into positive control and treatment subgroups. The four treatment groups were randomly allocated to a single MET treatment or MET combined with supplements either CHO, TAU, or both.

Diabetic rats exhibited elevated levels of glucose, insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), glycated hemoglobin%, lipid markers, aspartate aminotransferase, and malondialdehyde, along with reduced levels of antioxidant enzymes (catalase and superoxide dismutase). The administration of CHO and TAU supplements alongside MET in diabetic rats led to a noticeable recovery of islet mass. The antioxidative, anti-inflammatory, and anti-apoptotic properties of the proposed combination therapy significantly ameliorated the aforementioned abnormalities.

The supplementation of CHO and TAU with MET showed the potential to significantly improve metabolic parameters and protect against diabetic complications through its antioxidative, anti-inflammatory, and anti-apoptotic effects.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks an actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure is often encountered due to inherent or acquired resistance to chemotherapy. Previous studies implicated PI3K/Akt/mTOR signaling pathway in cancer stem cells (CSCs) enrichment and hence chemoresistance. The present study aimed at investigating the potential effect of piperine (PIP), an amide alkaloid isolated from Piper nigrum, on enhancing the sensitivity of TNBC cells to doxorubicin (DOX) in vitro on MDA-MB-231 cell line and in vivo in an animal model of Ehrlich ascites carcinoma solid tumor. Results showed a synergistic interaction between DOX and PIP on MDA-MB-231 cells. In addition, the combination elicited enhanced suppression of PI3K/Akt/mTOR signaling that paralleled an upregulation in this pathway's negative regulator, PTEN, along with a curtailment in the levels of the CSCs surrogate marker, aldehyde dehydrogenase-1 (ALDH-1). Meanwhile, in vivo investigations demonstrated the potential of the combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities. Notably, the combination failed to change cleaved poly-ADP ribose polymerase levels suggesting a pro-necrotic rather than pro-apoptotic mechanism. Overall, these findings suggest a potential role of PIP in decreasing the resistance to DOX in vitro and in vivo, likely by interfering with the PI3K/Akt/mTOR pathway and CSCs.

We evaluated whether thymol (THY) (30 mg/kg b.wt) could relieve the adverse effects of the neonicotinoid insecticide imidacloprid (IMD) (22.5 mg/kg b.wt) on the liver in a 56-day oral experiment and the probable underlying mechanisms. THY significantly suppressed the IMD-associated increase in hepatic enzyme leakage. Besides, the IMD-induced dyslipidemia was considerably corrected by THY. Moreover, THY significantly repressed the IMD-induced hepatic oxidative stress, lipid peroxidation, DNA damage, and inflammation. Of note, the Feulgen, mercuric bromophenol blue, and PAS-stained hepatic tissue sections analysis declared that treatment with THY largely rescued the IMD-induced depletion of the DNA, total proteins, and polysaccharides. Moreover, THY treatment did not affect the NF-kB p65 immunoexpression but markedly downregulated the Caspase-3 in the hepatocytes of the THY+IMD-treated group than the IMD-treated group. Conclusively, THY could efficiently protect against IMD-induced hepatotoxicity, probably through protecting cellular macromolecules and antioxidant, antiapoptotic, and anti-inflammatory activities.