Journal of Molecular Histology最新文献

Fluoride is commonly used in dentistry to prevent dental caries, however, excessive exposure may pose risks to soft tissues, particularly the kidneys, which are responsible for approximately 60% of fluoride excretion. Diabetic nephropathy, a major complication of diabetes mellitus, may share pathogenic pathways with fluoride-induced renal toxicity. However, the combined effects of chronic hyperglycemia and fluoride exposure on kidney cells remain poorly understood. This study investigated the effects of fluoride on murine renal tubular epithelial cells (M-1) and on murine kidneys under normal and hyperglycemic conditions. M-1 cells were cultured under high-glucose conditions (22.5 mM) and/or treated with fluoride (1 µM or 5 µM) for 24 to 72 h. Diabetic C57BL/6J mice received drinking water containing fluoride (10 mgF/L or 50 mgF/L) for 21 days. Evaluations included cell viability and morphology in vitro, collagen deposition in renal tissue by birefringence analysis, and expression of the kidney injury marker KIM-1 by immunofluorescence in both models. M-1 cells exposed to fluoride alone showed increased viability at 72 h, while KIM-1 expression was elevated in high-glucose and high-glucose + 1 µM fluoride conditions, suggesting a stress or adaptive response. In diabetic mice, glomerular collagen accumulation, indicative of early fibrosis, was observed but attenuated by fluoride treatment. However, high KIM-1 levels in fluoride-treated diabetic mice, particularly at the higher dose, indicated potential kidney injury. These results highlight a complex, dual role of F in the diabetic kidney, potentially protecting against glomerular fibrosis while exacerbating tubular injury at high doses. Careful monitoring of F exposure is needed, especially in areas with endemic fluorosis and high chronic kidney disease risk.

Electroacupuncture (EA) has been widely used in the clinical treatment of cognitive impairment after cerebral ischemia (CI) in China, but the specific molecular mechanism is not fully understood yet. In this study, permanent middle cerebral artery occlusion (pMCAO) model mice were administrated with EA therapy, Morris water maze (MWM) test was used for evaluation of cognitive function, Nissl staining was employed to quantify surviving neurons in the hippocampus, and enzyme-linked immunosorbent assay (ELISA) was utilized to detect the levels of amyloid beta (Aβ). The results showed that EA treatment obviously improved learning and memory abilities in the mice with pMCAO, inhibited neuronal loss in the hippocampus, and reduced the levels of Aβ40 and Aβ42. Meanwhile, we observed that METTL3 expression and total N6-methyladenosine (m6A) levels were significantly increased in the hippocampal tissues of pMCAO mice, which were reduced by EA therapy. Then, hippocampal neuronal cell line HT22 was induced by oxygen-glucose deprivation (OGD) to verify the molecular regulatory mechanism in vitro, and we found that METTL3 upregulated BACE1 expression in OGD-induced HT22 cells through promoting m6A enrichment on BACE1 mRNA, thus facilitating Aβ production and cell apoptosis of OGD-induced HT22 cells. Finally, through in vivo functional recovery experiments, we demonstrated that EA therapy restrained the METTL3/BACE1 axis to alleviate Aβ accumulation and cognitive dysfunction in pMCAO model mice. In summary, our data reveals that the m6A-modified BACE1 pathway is one of the molecular targeting mechanisms for EA treatment in cognitive impairment after CI.

Pimpinella brachycarpa has been used in food and traditional herbal medicine for its anti-inflammatory and antimicrobial properties. This study evaluated the therapeutic potential of P. brachycarpa extract (PBE) in a rat model of ligature-induced periodontitis and identified its active compounds, such as green tea catechin (GTC), chlorogenic acid (CGA), and their combination (MIX). Seven-week-old rats received PBE (150–300 mg/kg/day) for 14 days post-ligation to induce periodontitis. Outcomes were assessed using gross morphology, histology, TRAP staining, and immunohistochemistry. UPLC revealed CGA as a major constituent in PBE. PBE significantly reduced alveolar bone loss and inflammatory responses compared to the vehicle-treated ligature-induced periodontitis group (LIG), with effects comparable to or exceeding those of ISD (Zea mays L. extract and Magnolia cortex extract-containing herbal formulaas a reference drug), GTC, CGA, and MIX. TRAP and IHC analyses indicated suppression of osteoclast activity and decreased expression of CD45, IL-1β, and TNF-α. These findings suggest that PBE mitigates periodontitis via modulation of osteoclastogenesis and immune responses. Given its efficacy and bioactive profile, PBE may serve as a promising candidate for the development of natural therapeutics against periodontal disease.

This study aims to see the individual and combined effects of Angiotensin II type 2 (AT2) receptor agonist buloxibutid (also known as Compound 21 or C21) and sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin (EMPA) on effects of hypertension (HT), which is common today, on the heart, and vascular tissue. Male rats of the Sprague Dawley were divided into 5 groups: Control (C) group, HT group, HT + C21 group, HT + EMPA group and HT + C21 + EMPA group. After the protocol was completed, hemodynamic measurements were taken and heart and aorta tissues were evaluated biochemically, histopatologically and immunohistochemically. When the mean blood pressure (BP) values were compared, the mean BP of the HT group increased significantly compared to the C group (p < 0.05). Superoxide dismutase, glutathione and glutathione peroxidase activities in the heart, glutathione and catalase activities in the descending aorta were significantly higher in all treated groups compared to the HT group (p < 0.05). In the HT + C21 + EMPA group, histopathological damage score in hematoxylin–eosin (HE) stained heart sections compared to the HT group showed a decrease in tissue damage but cell infiltration was still observed. When HE staining method was applied, it was determined that the thoracic aorta sections in group C had normal histologic structure. In the HT group, dilatation in some parts and irregularities in elastic lamellae were observed. It was observed that the treated groups were similar to group C. When considering the individual and combined effects of C21 and EMPA, positive results on heart and vascular tissue were observed by hemodynamic, biochemical and histopathological analyses.

The pathogenesis of pelvic organ prolapse (POP) is associated with the decline in estrogen levels post-menopause, which ultimately weakens the mechanical properties of pelvic floor connective tissue. Regenerating (REG) family of proteins, particularly REG1B, regulates tissue repair and regeneration through the modulation of cell proliferation and extracellular matrix (ECM) remodeling. In this study, we utilized ovariectomized (OVX) mice, a recognized animal model for human menopause, to elucidate the mechanisms by which REG1B regulates the function of vaginal wall fibroblasts in POP. Expressions of REG1B and fibroblast-to-myofibroblast transition (FMT) markers in vaginal wall tissues from patients with POP and OVX mice were analyzed using immunohistochemistry and Western blot techniques. The effects of REG1B on the proliferation, migration, and invasion of mouse vaginal wall fibroblasts were evaluated using the Cell Counting Kit-8, cell scratch, and transwell invasion assays. REG1B’s impact on fibroblast collagen and ECM metabolism was examined via Western blot. Dual-luciferase reporter and chromatin immunoprecipitation assays validated the transcriptional regulation of REG1B mediated by estrogen receptor beta (ERβ) through direct binding to its promoter region. REG1B was downregulated in the vaginal wall tissues of patients with POP and OVX mice, whereas markers of FMT were upregulated. The knockdown of REG1B suppressed fibroblast proliferation, migration, and invasion, while simultaneously increasing the expression of FMT markers and promoting ECM remodeling. Activation of ERβ enhanced fibroblast proliferation, migration, and invasion by upregulating the expression of REG1B.This study elucidates the mechanism by which ERβ activation promotes fibroblast proliferation, migration, and invasion through REG1B, providing new insights for regenerative medicine approaches in pelvic floor reconstruction. These findings provide a theoretical foundation for understanding the mechanisms of POP and for developing REG1B-targeted preventive and therapeutic strategies.

The insulin-like growth factor 2 mRNA-binding protein (IGF2BP) family, comprises highly conserved RNA-binding proteins that play crucial roles in post-transcriptional gene regulation. Recent evidence suggests that IGF2BP proteins contribute to the pathogenesis and progression of multiple cancers and also participate in the regulation of viral infections and virus-associated tumors. This review provides a systematic synthesis of the biological functions of the IGF2BP family and its regulatory roles in viral life cycles. Particular emphasis is placed on oncogenic viruses, including hepatitis B and C viruses, human papilloma virus, Epstein–Barr virus, and human immunodeficiency virus, which co-opt IGF2BP proteins to promote viral replication and support tumorigenic processes. These mechanisms include the stabilization of viral RNA, modulation of host metabolic pathways, and immune responses. Furthermore, this review evaluates the therapeutic potential of targeting IGF2BP proteins in virus-associated tumors, offering new insights and future directions for research in this area.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, with heart failure representing a major end-stage condition characterized by profound myocardial energy deficiency. Cellular signaling in heart disease is highly complex, particularly within pathways involving microRNAs (miRNAs), signal transducer and activator of transcription 3 (STAT3), and Cyclophilin D, which together form regulatory networks governing cardiomyocyte survival and apoptosis. This review examines the emerging miRNAs–STAT3–Cyclophilin D–apoptosis axis as a potential molecular framework through which phosphocreatine (PCr) may exert cardioprotective effects in heart failure. Current literature on the roles of miRNAs and STAT3 in cardiac function and apoptotic regulation is systematically summarized, with particular emphasis on evidence linking PCr to modulation of these signaling pathways. Experimental and preclinical studies suggest that PCr may influence cardiomyocyte survival by modulating STAT3 activity through miRNA-mediated mechanisms and by affecting Cyclophilin D–dependent mitochondrial pathways. Several STAT3-associated miRNAs have been implicated in the cytoprotective effects observed in PCr-treated cardiomyocytes. Collectively, the available evidence supports the concept that the miRNAs–STAT3–Cyclophilin D–apoptosis pathway represents a relevant regulatory axis in heart failure pathophysiology and a potential target for PCr-based therapeutic strategies. Further experimental and clinical studies are required to clarify the mechanistic details and translational relevance of this proposed pathway.

An increasingly important factor in the development of acute respiratory distress syndrome (ARDS), a potentially fatal outcome of acute lung injury (ALI), is ferroptosis, a type of controlled cell death caused by excess iron and lipid peroxidation. To mimic the inflammatory response seen in sepsis, animal models of inflammation are often exposed to lipopolysaccharide (LPS) to induce ALI. The current research aims to examine how MIB2 (Mindbomb E3 ubiquitin ligase 2) interacts with ferroptosis by regulating GPX4, an important anti-ferroptotic protein, and how this contributes to the development of LPS-induced ALI. The results show that MIB2 expression is significantly increased in ALI models caused by LPS, and that inhibiting MIB2 in both in vivo and in vitro models reduces LPS-induced ferroptosis and boosts the inflammatory response. MIB2 was found to accelerate GPX4 degradation through a ubiquitination-dependent mechanism, leading to the initiation of ferroptosis during LPS-induced ALI. Furthermore, knocking down GPX4 was shown to reverse the protective effects of MIB2 knockdown on ferroptosis, emphasizing the critical role of MIB2-GPX4 regulation in ALI development. These findings shed light on the molecular processes of ferroptosis in ALI and suggest MIB2 as a potential therapeutic target for reducing or preventing LPS-induced lung damage.

The present study aimed to investigate the protective effects of curcumin (CMN) against methotrexate (MTX)-induced nephrotoxicity in rats. Eighteen male Wistar albino rats were randomly assigned to three equal groups. The control group received 1 mL/kg dimethyl sulfoxide intragastrically for 14 days. The MTX group received a single intraperitoneal dose of 20 mg/kg of MTX on the eleventh day of the experiment. MTX + CMN group received 100 mg/kg/day of CMN (dissolved in dimethyl sulfoxide) intragastrically for 14 days and a single intraperitoneal dose of 20 mg/kg of MTX on day eleven. At the end of the experiment, samples were collected for biochemical, histological and immunohistochemical analyses. MTX administration significantly elevated serum levels of urea, creatinine, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), and induced marked histological damage and renal fibrosis compared to the control group. Immunohistochemical analysis revealed significantly increased immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor-kappa B (NFkB), tumor necrosis factor-alpha (TNFα), and prokineticin-2 (PK2) in the MTX group compared to control group. In contrast, nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) immunoreactivity were markedly reduced. CMN treatment significantly improved biochemical and histological alterations and reduced collagen deposition in renal tissue. Furthermore, CMN markedly attenuated NFkB, TNFα, PK2, and Keap1 immunoreactivity, while enhancing Nrf2/HO-1 immunoreactivity induced by MTX administration. These findings suggest that CMN may serve as a potential therapeutic strategy for mitigating MTX-induced nephrotoxicity through anti-inflammatory, antioxidant, and antifibrotic mechanisms, possibly mediated by modulation of NFkB, TNFα, PK2, and Keap1/Nrf2/HO-1 signaling pathways.

Background

Ghanaian alcoholic bitters are widely consumed for their perceived health benefits. However, the liver and kidneys are susceptible to damage as a result of alcohol intake. There is however, limited research on the effects of Ghanaian herbal alcoholic bitters on the liver and kidney, and whether cocoa supplementation offers any protection.

Aim

To assess the effects of Ghanaian alcoholic bitters on the liver and kidneys of rats and to determine the protective role of natural cocoa powder.

Materials and methods

Twenty-four Sprague Dawley rats were randomly assigned to four groups: Control, Alcoholic Bitters, Natural Cocoa Powder, and Alcoholic Bitters + Natural Cocoa Powder. The intervention lasted 63 days, after which liver and kidney tissues were harvested and processed for histological analysis. Slides were examined using light microscopy, and histopathological changes were scored using a modified staging and grading system.

Results

The Natural Cocoa Powder showed the most severe hepatic steatosis while the Alcoholic Bitters exhibited marked hepatocyte ballooning, confluent necrosis, Mallory-Denk bodies, and inflammatory cell infiltration. Co-administration of cocoa powder with bitters mitigates the liver changes to some extent. In kidney tissues, moderate interstitial and glomerular hemorrhages were observed, suggesting acute kidney injury.

Conclusion

Natural cocoa powder demonstrated a partial protective effect against alcoholic bitters-induced liver injury. Prolonged exposure to alcoholic bitters, with or without cocoa, led to adverse kidney changes, and cocoa co-administration did not significantly mitigate these effects. Further research is needed to clarify the mechanisms behind cocoa-induced liver and kidney alterations and to validate these findings.