Tissue & cell最新文献

Without doubt, liver injury and immunotoxicity are patently interconnected. The liver's role as a leading regulator of the immune system is compromised in advanced liver illness, which may cause immune dysfunction. The liver disorders, when they deteriorate the immunity, making it more vulnerable to systemic damage, while certain chemicals can induce liver injury through direct immune responses. Branch-chain amino acids (BCAAs) are indispensable amino acids immensely recommended as pharmacological nutrients for those with chronic liver diseases to restrict the development of systemic complications caused by toxicants. The aim of this dietary treatment for CCl4-induced liver immunotoxicity and remote disorders is to recruit branched-chain amino acids enriched in the protein diet to achieve therapeutic effectiveness. In the current design, 40 male Wister rats (n = 10 per group) were randomly divided into four equal groups: The study included four groups: control, CCl4, CCl4 +BCAAs, and CCl4 +protein diet. Histomorphological analysis was conducted using toluidine blue and Masson's trichrome stains, and immunohistochemical assessment employed the caspase-3 gene as a marker, and standard diagnostic methods were applied to evaluate liver biomarkers. Poisoning by CCl4 emphasized a significant increase in liver transaminases, and unlimited histomorphological deteriorations elicited by severe fibrosis. Significant apoptosis was also demonstrated by the elevated apoptotic expression of caspase-3 in the target tissues. Concurrent supplementation of BCAAs with dietary protein following CCl4 administration returned histomorphological and immunohistochemical alterations to normal architecture and downregulated caspase-3 expression, which correlated with decreased transaminases. Fundamentally proposed that CCl4-induced rats administered a protein diet mainly of plant origin, concomitant with BCAAs, were immunologically effective not only in reducing liver cirrhosis but also as coadjuvant treatment for specific lesions.

Overcoming therapeutic resistance remains one of the most critical challenges in the clinical management of non-small cell lung cancer (NSCLC). Most systemic therapies for advanced NSCLC rely on intact apoptotic execution, which inherently limits their durability once apoptotic competence is lost. In many advanced tumors, apoptosis is disrupted by TP53 dysfunction, persistent activation of anti-apoptotic survival programs, or epigenetic repression of death-executing genes, allowing malignant cells to persist under sustained therapeutic pressure. In this context, pyroptosis has emerged as an alternative regulated cell-death program that operates independently of classical apoptotic machinery. Unlike apoptosis, pyroptosis is driven by gasdermin-mediated membrane permeabilization and the release of pro-inflammatory mediators capable of reshaping local immune responses, making it particularly attractive for apoptosis-resistant tumors. This review examines recent advances in pyroptosis-inducing nanomedicines for apoptosis-resistant NSCLC, with a specific focus on delivery-relevant mechanisms, gasdermin activation nodes, immune remodeling effects, and key barriers to clinical translation. We discuss how tumor-responsive nanocarriers can be engineered to deliver inflammasome activators, redox-sensitive agents, epigenetic modulators, or caspase triggers selectively to malignant tissue, thereby minimizing off-target inflammation. Through controlled engagement of the caspase-1/GSDMD or caspase-3/GSDME axes, these systems induce localized membrane disruption, cytokine release, and enhanced antigen presentation in preclinical models. In selected settings, nano-enabled pyroptosis promotes immune cell infiltration and restores responsiveness to PD-1/PD-L1-based immunotherapy, particularly when combined with chemotherapy or radiotherapy. Despite these advances, clinical translation remains constrained by tumor heterogeneity, delivery inefficiency, and the need for stringent control of inflammatory spillover in lung tissue.

Diabetes mellitus, marked by chronic hyperglycemia and systemic inflammation, causes oxidative stress and multi-organ damage. Marine macroalgae like Dictyota ciliolata contain polyphenols and flavonoids with potential therapeutic effects on metabolic disorders. This study examined the antidiabetic, hepatoprotective, antioxidant, and anti-inflammatory effects of Dictyota ciliolata extract in alloxan-induced diabetic rats. Adult male Wistar rats were allocated into four groups: normal control, diabetic control, diabetic treated with metformin (5 mg/kg), and diabetic treated with Dictyota ciliolata extract (200 mg/kg) for 21 days. Assessments included fasting blood glucose, serum insulin, liver enzymes (ALT, AST, ALP), lipid profile, oxidative stress biomarkers (MDA, SOD, CAT, GPx), pro-inflammatory cytokines (IL-6, TNF-α), and transcription factors (NF-κB). Gene expression of metabolic regulators (PPAR-γ, GLUT4, IRS-1, Nrf2, AMPK) was analyzed via qRT-PCR. Histopathological examination of the liver and pancreas was conducted to assess tissue-level effects. Treatment with Dictyota ciliolata reduced fasting blood glucose by approximately 38 % and increased serum insulin levels by 55 % compared with diabetic controls. The extract restored liver enzyme profiles and lipid parameters while increasing antioxidant enzyme activities by more than 40 % and significantly reducing lipid peroxidation. Furthermore, the extract modulated the levels of inflammatory cytokines. Gene expression analysis confirmed upregulation of PPAR-γ (0.70-fold), GLUT4 (1.42-fold), AMPK (1.17-fold), IRS-1 (1.36-fold), and Nrf2 (1.49-fold) relative to diabetic controls. Histopathological findings supported the biochemical results, revealing preserved hepatic architecture with limited pancreatic recovery. Dictyota ciliolata ethanolic extract exerts multifaceted protective effects in diabetic conditions via regulation of glycemia, oxidative stress, and inflammatory signaling. These findings highlight its potential as a natural therapeutic candidate for diabetes management.

An important consequence of diabetes is diabetic nephropathy (DN), which could end up in end-stage renal failure and chronic kidney disease. Blood glucose control, reduction of inflammation, management of oxidative stress, enhancement of autophagy, and repair of renal injury and fibrosis are important strategies for the management of DN. This research examined the protective benefits of berberine hydrochloride liposomes (BHC-Lip) and/or vildagliptin (Vild) against DN in rats with high-fat diet/streptozotocin (HFD/STZ) were examined in this investigation. The rats were separated into four diabetic groups and a control group. These groups are T2DM, T2DM-BHC-Lip, T2DM-Vildagliptin (Vild), and T2DM-BHC-Lip-Vild groups. BHC-Lip or Vild treatment significantly restored antioxidant capacity, resulting in decreased MDA and elevated GPx, SOD, and GSH levels in renal tissues, with combined therapy producing the most powerful effect. The combined therapy significantly improved renal function biomarkers, including creatinine, urea, sodium, and potassium levels, restoring them to nearly control levels. Furthermore, BHC-Lip or Vild treatments markedly reduced serum inflammatory cytokines and upregulated autophagy-related gene expression, with increased expression of Beclin-1 and LC3, and decreased expression of PI3K/Akt/mTOR/P62 signaling. In contrast, combination therapy produced superior autophagic activation and suppression of pro-inflammatory pathways. Furthermore, there was a noticeable improvement in kidney damage and fibrosis indicators (nephrin and higher nestin, desmin, and vimentin), especially those receiving combined treatment. Histopathological examination supported these findings, showing significant improvement in kidney architecture. Together, our findings show that Vild and BHC-Lip work in concert to prevent DN through lowering oxidative stress and inflammation, boosting autophagy, and reducing renal structural damage.

Dibutyl phthalate (DBP) is a member of phthalate esters which are considered as potent environmental toxicant owing to their damaging effects on different organs including testis. Glabridin (GLN) is a polyphenolic substance that is found in the roots of Glycyrrhiza glabra and exhibits a wide range of pharmacological activities. This research investigation explored the ameliorative potential of GLN against DBP instigated testicular toxicity. Forty-eight male Sprague Dawley rats were categorized into control, DBP (200 mg/kg), DBP (200 mg/kg) + GLN (50 mg/kg), and GLN (50 mg/kg) group. We found that DBP administration exacerbated the gene expression of β-catenin, WNT1, and TCF7L2 while suppressed the gene expression of APC, AXIN1 as well as GSK3β. Furthermore, DBP exposure promoted the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) while suppressing the activities of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), glutathione reductase (GSR), glutathione Peroxidase (GPx), catalase (CAT), and glutathione (GSH). Moreover, DPB administration exacerbated Caspase-9, Bax and Caspase-3 while diminishing Bcl-2 concentrations. A notable escalation was observed in the levels of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and nuclear factor- kappa B (NF-κB) following the administration of DBP. Besides, DBP intoxication distorted the normal morphology of testicular tissues. Nonetheless, GLN therapy significantly alleviated testicular impairments via regulating aforementioned biochemical and histological abnormalities. These findings suggest he palliative efficacy of GLN against DPN induced testicular damages thereby recommending the use of GLN to promote reproductive health in male.

The increasing prevalence of antibiotic resistance and pathological inflammation underscores the importance of understanding the underlying biochemical and immune processes that govern the host-pathogen interface. Nutrient deficiency, compounded by antibiotic-induced nutrient depletion, forms a vicious cycle of overt inflammation, contributing to bacterial toxin translocation in human inter-organ and intra-organs milieus. Coenzyme Q10 (CoQ10) and omega-6 linoleic acid (LA 18:2ω6) are integral to cellular membrane integrity and immune defense. However, the complex enzymatic steps at the host cell-pathogen interface remain poorly understood. This study is particularly timely, as it explores these knowledge gaps, which can inform the development of nutritional and therapeutic strategies that modulate or target these mechanisms. Using an infectious-inflamed cell co-culture model of the gut-liver axis, we exposed triple cell co-cultures of human intestinal epithelial cells (T84), macrophage-like THP-1 cells, and hepatic cells (Huh7) to linoleic acid-producing Lactobacillus casei (L. casei) and Pseudomonas aeruginosa strain PAO1 (PAO1). The cultures were incubated for 6 h in medium with or without ceftazidime antibiotic. PAO1 and L. casei exerted opposing effects on the secretion of Th1 cytokines IL-1β, IL-6, and the Th 2-type cytokine IL-10. Inoculation with PAO1 decreased CoQ10 and linoleic acid levels compared to uninfected controls. L. casei restored cellular health and biofunctionality impaired by PAO1, indicating its benefit to the host's well-being. The antibiotic ceftazidime exerted dual effects, alleviating PAO1 toxicity while marginally disrupting the beneficial effects of L. casei. Our results show how the vicious cycle of nutrient deficiency and antibiotic-induced nutrient loss reinforces pathological inflammation at the host cell-pathogen interface and highlights the need for more appropriate targeted antibiotic use that preserves essential nutrients like CoQ10 and omega-6 fatty acids. Inflammatory responses driven by opportunistic pathogens and LA-producing bacteria represent opposing immunometabolic pathways that may provide insights into novel approaches for treating infection and reducing antibiotic resistance.

Aquaculture has become a global major economic sector that requires constant innovation. One of the main problems facing aquaculture systems is infectious disorders, particularly bacterial diseases, which reduce aquaculture's viability and cause significant economic losses. Fish mostly use innate or non-specific immunity to protect themselves from different microbial infections. Of the numerous Pattern Recognition Receptors (PRRs), Toll-like receptors (TLRs) are the earliest and best-characterized innate immune receptors. In the current study, the immunohistochemical expression patterns of TLR4 in the renal, hepatic, and splenic tissues of Oreochromis niloticus (O. niloticus) and Mugil cephalus (M. cephalus) were examined and compared. In addition, correlation between TLR-4 expression and the severity of histopathological lesions was also performed. Our findings revealed a strong positive immune reaction of the hepatic, splenic, and renal tissues of O. niloticus to TLR4, while M. cephalus exhibited moderate expression of TLR4 in the same organs when compared to O. niloticus. This upregulation of TLR4 expression was consistent with the histological alterations that were obviously seen in the examined tissues. The present investigation demonstrated that O. niloticus had significantly more severe histological abnormalities compared to M. cephalus. By providing important new information about the relationship between pathological findings and molecular immune activation, this comparative study advances our understanding of host-pathogen interaction. However, more research is required to highlight the differentially expressed immune-related genes and signaling pathways involved in defense mechanisms against bacterial infections in different species, infected with the same microorganisms.

Background: CAP2 influences cellular behavior by regulating actin dynamics, and it is upregulated in malignant melanoma. The investigation intended to explore the mechanism of CAP2 in skin cutaneous melanoma (SKCM).

Methods: Based on TCGA-SKCM and GTEx databases, the expression, clinical relevance, and potential molecular functions of CAP2 in SKCM were investigated using bioinformatics analysis. CAP2 expression in SKCM cell lines and normal cells was detected. CAP2 was knocked down in SKCM models, including A375 cells and subcutaneous nude mouse xenografts, to evaluate its involvement in tumor development and epithelial-mesenchymal transition (EMT)-like processes. TLR4 and p-NF-κB p65 levels were detected by Western blot. Dual-luciferase reporter assay and co-immunoprecipitation were used to explore the interaction between CAP2 and TLR4. TLR4 was overexpressed in SKCM models to further validate the underlying mechanism of CAP2 in SKCM.

Results: Bioinformatics analysis indicated that the high expression of CAP2 in SKCM patients was associated with poor prognosis and had potential diagnostic value. Its function might be correlated with the Toll-like receptor (TLR) pathway. CAP2 was highly expressed in SKCM cell lines. CAP2 knockdown markedly suppressed tumor progression and EMT-like processes both in vivo and in vitro. Additionally, CAP2 knockdown significantly inhibited TLR4/NF-κB pathway. Notably, CAP2 regulated the activation of TLR4 at the transcriptional level. Overexpression of TLR4 partially altered the effects of CAP2 knockdown.

Conclusion: CAP2 accelerates SKCM development by promoting EMT-like processes through TLR4/NF-κB pathway. CAP2 may be a novel biomarker for SKCM management. Nevertheless, these findings require further validation in clinical studies.