Mondia whitei is used traditionally for treating hypertension and erectile dysfunction; however, the toxicological profile of its fruit has not been fully established. This study evaluated the toxicological effect of the aqueous extract of Mondia whitei fruit (AEMWF) in Wistar rats. In the acute toxicity study, a single dose (5000 mg/kg) of AEMWF was administered orally to rats. In the sub-acute toxicity test, rats were administered AEMWF orally at 500, 750, and 1000 mg/kg for 28 days. Behavioural and physiological parameters were recorded weekly. After sacrificing the rats via anaesthesia (diethyl ether), blood and vital organs were obtained for haematological, biochemical, and histological assessments. No signs of toxicity were observed in the acute toxicity study. In the sub-acute toxicity study, no significant changes were observed in the body weight of rats, except for 750 mg/kg AEMWF administered male rats, where a significant (p < 0.05) increase was observed at week 3 compared to the control. No significant difference was observed in the haematopoietic system, serum liver and kidney function markers, and tissue oxidative stress biomarkers. However, results showed a significant (p < 0.05) decrease in urea level in female rats administered 500 mg/kg AEMWF, and a significant (p < 0.05) increase in albumin level in rats administered 1000 mg/kg AEMWF, when compared with the control. Histological changes were only noted at 1000 mg/kg AEMWF. The AEMWF at 500 and 750 mg/kg could be considered safe for consumption. Hence, this study recommends chronic toxicological testing for future studies.

Genetic and non-genetic drivers of histological progression and regression in MASLD.

Protective role of cichoriin and inulin against HFD-STZ-induced diabetic cardiomyopathy in mice via oxidative stress suppression and metabolic modulation.

How does the traditional Chinese compound Bushen Xiaozheng Decoction (BSXZD) affect the immunosuppressive microenvironment in rat endometriosis models? Sprague Dawley rats were randomly divided into normal, sham operation, model, Yasmin, and low-, medium-, high-dose BSXZD groups with 10 rats in each group. The endometriosis model was established by autologous endometrial transplantation, and corresponding interventions were given for 28 days. The volume of ectopic lesions was measured, and histological changes of endometrium were observed by hematoxylin-eosin staining. The protein or gene expression of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in serum or endometrium was detected by immunohistochemistry, quantitative real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Following treatment with BSXZD, the pseudostratified phenomenon and cavity structure of endometrial cells were reduced. Additionally, the expression levels of IL-10 and TGF-β in both endometrium and serum were significantly decreased, accompanied by a marked reduction in the volume of ectopic lesions. BSXZD can significantly inhibit the growth of ectopic lesions in a rat model of endometriosis. The underlying mechanism may involve dual regulation of the endocrine-immune axis: it not only directly downregulates the expression of the immunosuppressive factors IL-10 and TGF-β to reversing the local immunosuppressive microenvironment, but also indirectly modulates these cytokines via sex hormone-related signaling pathways. Further studies are needed to clarify the precise molecular mechanism.

Foeniculum vulgare, commonly known as fennel, has a long history of use in traditional medicine, particularly for treating problems related to the digestive, endocrine, reproductive, and respiratory systems. The major constituents found in fennel seed extracts are trans-anethole (68.6%-75.0%), fenchone (8.40%-14.7%), and methyl chavicol (5.09%-9.10%). However, before introducing this plant into the human environment, it is essential to understand its toxicological properties. In this study, we investigated the acute and sub-acute toxicity of methanolic extracts of F. vulgare. A phytochemical screening was performed to identify the major chemical constituents of the plant. For the acute toxicity study, female Wistar rats received a single dose of the methanolic extract of F. vulgare at doses of 1000, 2000, 3000, and 5000 mg/kg for 14 days. In the sub-acute toxicity study, the methanolic extract of F. vulgare was administered orally daily at doses of 125, 250, and 500 mg/kg for 28 days. Hematological, biochemical, and histological changes were evaluated. Phytochemical tests were also performed. The phytochemical analysis showed that the methanolic extract of F. vulgare is rich in flavonoids, catechic, gallic tannins, and total polyphenols. Toxicological tests showed no animal deaths, suggesting that the LD50 was greater than 5000 mg/kg. In the sub-acute oral toxicity study, no significant differences were observed in body weight, food consumption, or water intake. Additionally, there were no significant changes in hematological and biochemical parameters or differences in the macroscopic and microscopic examination of organs. Therefore, this study concludes that the methanolic extract of F. vulgare, at the doses tested, is considered non-toxic under the conditions evaluated.

Galangin enhances skin flap survival by inhibiting ferroptosis via SIRT1-mediated FOXO1 deacetylation.

Swimming exercise attenuates diabetic myopathy and is associated with histological and mitochondrial changes in pregnant rats (Rattus norvegicus).

Background Galgeun-tang (GGT) is a traditional Korean multi-component formulation composed of several botanical drugs and has long been prescribed for febrile and musculoskeletal disorders. With the global rise in obesity and obesity-related metabolic diseases, there is increasing demand for safer and multi-targeted therapeutic strategies. However, the systemic metabolic effects and anti-obesity potential of GGT remain incompletely understood. Methods The anti-obesity effects of GGT were evaluated using a tiered experimental approach comprising C2C12 myotubes, high-fat diet (HFD)-induced obese C57BL/6J mice, and Caenorhabditis elegans ( C. elegans ) exposed to high-glucose conditions. In vitro analyses assessed glucose uptake, gene expression, and protein signaling pathways. In mice, body weight, glucose tolerance, serum biochemical parameters, histological changes, and hepatic and adipose gene expression were examined. In C. elegans , lifespan, lipid and glucose accumulation, and insulin signaling–related gene expression were analyzed following treatment with GGT or metformin (MET). Results GGT enhanced glucose uptake and increased the expression of insulin-responsive and mitochondrial regulatory genes in C2C12 myotubes. In HFD-fed mice, GGT attenuated body weight gain, improved glucose tolerance and insulin sensitivity, and alleviated hepatic steatosis and adipose hypertrophy, accompanied by suppression of lipogenic genes and induction of β-oxidation markers. In C. elegans , GGT reduced lipid and glucose accumulation, prolonged lifespan, and modulated the expression of insulin signaling–related genes, including daf-16 and daf-2 . Across models, GGT exerted metabolic benefits in a dose- and context-dependent manner, with effects comparable to those of MET. Conclusion GGT improves obesity-related metabolic dysfunction by coordinately regulating glucose homeostasis, lipid metabolism, and energy expenditure across cellular, nematode, and murine models. These findings provide preclinical evidence supporting GGT as a multi-targeted herbal intervention for obesity and metabolic disorders and warrant further targeted mechanistic studies and clinical investigations.

The protective effect of ascorbic acid against renal toxicity induced by combination antiretroviral drugs in rats was examined. Thirty-six female Wistar rats, weighing between 180 and 220 g, were divided into two equal groups (A and B) to represent short- and long-term administration, respectively. Each group was further subdivided into three subgroups (1, 2, and 3), resulting in a total of six subgroups (A1, A2, A3, B1, B2, and B3), with six rats in each. Subgroups A1 and B1 served as controls and received distilled water as a placebo. Subgroups A2 and B2 received combination antiretroviral therapy (cART) for 2 and 8 weeks, respectively, while subgroups A3 and B3 received co-administration of cART with ascorbic acid for the same periods. All treatments were administered via oral intubation. Serum levels of urea (U), creatinine (Cr), sodium (Na+), potassium (K+), chloride (Cl-), and bicarbonate (HCO3¯) were significantly higher (P<0.05) in subgroups A2 and B2 compared with controls (A1 and B1); conversely, serum levels of these parameters, except for Na+, decreased significantly (P<0.05) in subgroups A3 and B3 compared with A2 and B2. A significant (P<0.05) increase in serum levels of U, Cr, Na+, K+, and Cl- was observed in B1 compared with A1. A reduction in mean kidney weight and some pathological changes in kidney histology were noted in subgroups A2 and B2, but not in A3, B3, or the control groups. Overall, combination antiretroviral therapy (cART) showed nephrotoxic effects on renal function indices in female Wistar rats, whereas ascorbic acid demonstrated renoprotective effects.

Introduction Intervertebral disc degeneration (IDD) is a major cause of low back pain and disability. While MRI remains the standard diagnostic tool, it provides limited insight into the cellular and molecular changes underlying IDD. Histological analysis offers a complementary approach to characterizing the degenerative process in human intervertebral discs (IVDs). This systematic review aims to provide a comprehensive analysis of histological and immunohistochemical changes across the IVD, nucleus pulposus (NP), and cartilage endplate (CEP) in degenerated human discs. Methods A literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 2015 and 2025. A total of 45 human studies were included. Histological features, protein expression profiles, and grading systems were analyzed. Differentially expressed proteins were mapped into protein–protein interaction (PPI) networks using the STRING database. Results Common histopathological features included ECM disorganization, proteoglycan depletion, fibrosis, neovascularization, and cell clustering. Molecular data revealed upregulation of catabolic enzymes, inflammatory cytokines, apoptotic mediators, and angiogenic factors. Conversely, regenerative and protective markers were significantly downregulated. PPI analysis revealed region-specific pathways: ECM remodeling and BMP/VEGF signaling in the IVD, inflammation and mechanotransduction in the NP, and ossification and prostaglandin signaling in the CEP. Conclusion Histology reveals spatially distinct yet converging degenerative pathways across IVD regions. These findings identify potential biomarkers and therapeutic targets, supporting histological analysis as an essential complement to imaging for accurate IDD characterization.

Age-related alterations in the transverse carpal ligament (TCL) and the median nerve are thought to increase susceptibility to carpal tunnel syndrome in older individuals. This study aimed to investigate the mechanical properties of the TCL and histological changes in both the TCL and the median nerve in cadavers across a wide age range. Fifty formalin-embalmed cadavers (40-93 years old) were studied, yielding 100 TCL specimens. A digital palpation device (MyotonPRO) was used in situ to measure TCL dynamic stiffness, elasticity (logarithmic decrement), mechanical stress relaxation time, and creep at proximal, middle, and distal regions. After testing, each TCL and corresponding median nerve were excised. Masson's trichrome staining and scanning electron microscopy were performed to assess collagen fiber organization, fibroblast density, and nerve structure. Pearson's correlation was used to determine associations between TCL properties and age. An age-dependent increase in TCL stiffness was observed, alongside decreased elasticity, relaxation time, and creep. Histological analyses revealed reduced fibroblast density, disorganized collagen fibers with large clefts between bundles, and increased fine collagen meshwork in interfascicular matrix in older specimens. Furthermore, thinning of connective tissue layers surrounding the median nerve and diminished myelin sheaths were noted with advancing age. This cadaveric study reveals that the TCL stiffens and becomes structurally disorganized with advancing age, paralleled by degenerative changes in the median nerve. Such age-related alterations may predispose elderly individuals to a higher risk of carpal tunnel syndrome, underscoring the need for targeted preventive and therapeutic strategies.

Collagenase clostridium histolyticum-aaes (CCH-aaes) is FDA-approved for cellulite treatment but was withdrawn due to high bruising incidence. Histological effects of CCH-aaes in humans remain poorly characterized. To evaluate histopathologic changes in human subcutaneous tissue following CCH-aaes injection and compare injection techniques to identify strategies that reduce bruising. In this single-center, phase 2b, non-randomized, open-label exploratory study, eight women undergoing elective abdominoplasty received CCH-aaes injections using either a 3-aliquot or a 7-injection hexagonal grid technique. Dosing schedules varied across groups. Excised abdominal tissue was analyzed histologically and immunohistochemically. Pathologists were blinded to injection technique and timing. CCH-aaes induced targeted enzymatic subcision and remodeling (ESR) of subcutaneous tissue, with collagen degradation, neocollagenesis, and fat lobule reorganization. The 3-aliquot technique produced more localized, intense histologic changes and greater bruising, while the grid technique caused diffuse but milder tissue effects. Bruising correlated with subcutaneous vascular disruption rather than dermal injury. No serious adverse events occurred. AUX-I (clostridial collagenase I-one of the two purified bacterial collagenases in CCH-aaes) neutralizing antibodies developed in 5 of 8 subjects, with no impact on safety or efficacy. CCH-aaes induces localized subcutaneous remodeling without dermal disruption. The 3-aliquot technique elicits more robust histologic effects but increases bruising risk, while the grid method offers a more diffuse, potentially safer alternative. These findings clarify the tissue-level mechanism of CCH-aaes and may guide safer clinical use should the product return to market.

Early application of sodium valproate has a certain protective effect on important organ functions. This study aimed to investigate the protective effects of sodium valproate on rats with severe thermal injury combined with seawater immersion followed by delayed intravenous infusion. Rats were divided into three groups: scald (S) group, scald with seawater immersion (SS) group, and scald with seawater immersion treated with sodium valproate (SSV) group. All rats received a 35% of total body surface area full-thickness scald and delayed rehydration 2h after injury. SS and SSV groups were immersed in artificial seawater (23℃, 30min) immediately after scalding, and the SSV group was subcutaneously injected with sodium valproate (300mg/kg) after seawater immersion. Physiological parameters, organ functions, blood flow, and histological changes in abdominal organs were assessed. The 24-h survival rate was significantly lower in the SS group (55%) compared to the S (90%) and SSV (75%) groups. Sodium valproate treatment in the SSV group significantly improved physiological indicators, organ functions, and abdominal organ blood flow compared to the SS group. Pathological damage, especially to the heart, brain, liver, kidney, and intestine, was reduced in the SSV group. Early administration of sodium valproate during delayed resuscitation following severe scald and seawater immersion improves the 24-h survival rate, hemodynamics, and organ function.

Silibinin-loaded PEGylated niosomal nanoparticles restore hippocampus histological changes, memory and learning, and downregulate the inflammasome pathway in Alzheimer's disease animal models.

Bladder pain significantly impacts millions worldwide, severely affecting their quality of life and posing a major clinical challenge. Understanding the mechanisms underlying persistent bladder pain is critical for developing better therapeutic strategies. In this study, we investigate the effects of cyclophosphamide (CYP)-induced persistent bladder sensitization to explore the lateralized contribution of amygdala calcitonin gene-related peptide receptors (CGRP-Rs) on pain-like changes in mice. We demonstrate that CYP induces hypersensitivity lasting up to 14 days postinjury (DPI) in the urinary bladder distention assay and up to 21 DPI when assessing abdominal mechanical sensitivity. Despite persistent pain-like changes, no significant bladder histological changes were observed. Based on previous findings that CGRP signaling from the parabrachial nucleus contributes to central amygdala (CeA) lateralization, we hypothesized that CGRP-Rs play a key role in driving visceral bladder pain-related hemispherical differences. We show that inhibiting CGRP-R activity with the antagonist CGRP8-37, in the right CeA attenuates bladder pain-like behavior, whereas left CeA inhibition sustains CYP-induced hypersensitivity. Electrophysiological recordings revealed increased firing frequency in CGRP-R-positive cells in the right CeA 7 DPI. In vivo single photon calcium imaging demonstrated increased Ca transients in CGRP-R-positive cells in the right CeA, upon the presentation of a stimulus at 0 DPI and overall at 2 DPI, further confirming the pronociceptive role of CGRP-Rs in the right CeA. Taken together, these findings provide a crucial foundation for understanding pain-induced CeA lateralization and for further studies identifying how targeting CGRP signaling could provide bladder pain relief.

The role of Race and Ethnicity in the response to MASLD treatment: A Review.

Since neuropathology departments in Germany are mainly located only at university hospitals, brain sections are frequently performed by general pathologists. This article provides practical recommendations for astructured approach and highlights situations in which neuropathological consultation is advisable. The recommendations are based on established procedures, current literature, and personal professional experience. They are intended as apractical guide rather than aformal guideline. Key steps for removal, fixation, and sectioning as well as interpretation of the findings are described. Hereby, the importance of clinical information and of asystematic assessment of macroscopic and histological changes is emphasized. Furthermore, typical situations are described in which neuropathological expertise is recommended. Astructured brain section enhances the overall quality of the autopsy. It enables avalid integration of cerebral changes into abroader context. Close collaboration between pathology and neuropathology is essential and beneficial for both sides.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition, closely associated with obesity and type 2 diabetes mellitus. Despite its prevalence, there are no approved pharmacotherapies, making the search for effective treatments crucial. This study investigates the impact of vertical sleeve gastrectomy (VSG) on NAFLD, focusing on changes in bile acid metabolism as a potential therapeutic mechanism. We employed an ApoE-/- mouse model to simulate human NAFLD conditions. Mice were divided into two groups: one underwent VSG and the other served as a control. We monitored body weight, food intake, liver function, lipid profiles, and histological changes in hepatic tissues. Bile acid profiles were analyzed using Ultra Performance Liquid Chromatography coupled with Tandem Mass Spectrometry (UPLC-MS/MS). Post-VSG, mice exhibited significant weight loss and reduced food intake. Biochemical analyses showed substantial improvements in liver function tests (ALT and AST), lipid profiles (cholesterol and triglycerides), and glucose regulation. Histological examination revealed marked reductions in hepatic steatosis and inflammation. Notably, VSG led to significant alterations in bile acid profiles, particularly increased primary bile acids and decreased secondary bile acids, correlating with improved liver histology and metabolic parameters. Our findings suggest that VSG, beyond its role in weight reduction, significantly improves NAFLD. The surgery alters bile acid metabolism, which may contribute to its therapeutic effects. These results highlight the potential of VSG as a metabolic surgery for NAFLD and open avenues for exploring bile acid-related therapies.

Platelet-rich plasma contains a high concentration of platelets which can produce various types of growth factors that can promote tissue repair and reconstruction. Because of its controversial use in the treatment of alopecia, this study aimed to explore the effects of platelet-rich plasma on hair follicle growth in mice, so as to provide a theoretical basis for its clinical application. Twenty female C57BL/6 mice were randomly divided into experimental and control groups. The dorsal hair of the mice was removed, and the proliferating cells were labeled by 5-ethynyl-2'deoxyuridine nucleoside, platelet-rich plasma was injected subcutaneously into the depilation site of the experimental group, while the control group was injected with normal saline. Photographs were taken to record the dorsal hair growth in both groups. Histological changes in hair follicles were detected, and the expression of Wnt10b and proliferating cells within the follicles was analyzed. The experimental group showed faster hair growth than the control. The expression of Wnt10b in the experimental group was significantly higher than that in the control group; the location and intensity of its expression were consistent with that of the proliferating cells of the hair follicle. Subcutaneous injection of platelet-rich plasma correlates with increased expression of Wnt10b in hair follicles, which promotes the proliferation of hair matrix and inner hair root sheath cells, and accelerates the follicular cycling cycle, characteristics that make PRP a promising new option for the treatment of alopecia. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Physalis peruviana L. (Cape gooseberry) is susceptible to several pathogens, among which the sobemovirus physalis rugose mosaic virus (PhyRMV) is most prominent. This study investigated the anatomical, morphophysiological, and metabolic responses of P. peruviana to PhyRMV over the course of the infection cycle. P. peruviana plants were grown under greenhouse conditions (24 ± 2 ℃) and mechanically inoculated with buffer (mock) or PhyRMV inoculum. The local and systemic leaves were collected at 0, 3, 7, 14, 21, and 42days after inoculation (DAI) and viral infection was confirmed by RT-qPCR. Morphological traits, including plant height, symptoms, and the Falker chlorophyll index, and histological changes were evaluated in PhyRMV-infected plants and compared to mock-inoculated controls. To characterize and compare their metabolic profile, the collected leaves were processed and subjected to gas chromatography-mass spectrometry (GC-MS). Yield was also assessed by quantifying the number and weight of fruits. PhyRMV could be detected in systemic leaves from 14 DAI onward, accompanied by an increase in viral load and the intensification of the symptoms, including mosaic, chlorosis, and leaf deformation from 21 DAI onward, which were associated with reduced plant height and chlorophyll contents. At 42 DAI, histological changes and increased starch accumulation were observed in the infected leaves, suggesting impaired photoassimilate transport. GC-MS revealed an accumulation of sucrose, pyruvate, and tricarboxylic acid (TCA) cycle metabolites, possibly due to the high energy demand associated with viral replication, indicating significant alterations in the functioning of the central metabolic pathways in systemic leaves in the late stage of infection at 42 DAI. Compounds such as glutamate, isoleucine, and malonate could potentially be involved in the activation of defense pathways, including the shikimic acid pathway. Metabolic networks demonstrated a loss of complexity in the infected plants, indicating a redirection of resources from primary metabolism to defense-associated mechanisms. Thus, fruit production was reduced by 31% in the infected plants, highlighting a negative impact of infection on the production potential. These results support management strategies based on the induction of plant defense mechanisms and reinforce the importance of the use of integrative approaches to understanding the physiological and biochemical impacts of viruses on crops.