Search Results (2,473)

Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. Full article

Siniperca chuatsi is an important high-quality freshwater aquaculture species in China. In nature, it feeds exclusively on live food. In this study, domesticated juvenile S. chuatsi were divided into three groups and fed live food (group L), compound feed (group C), or a mixed diet (group M) for three months to investigate the molecular mechanisms underlying adaptation to compound feed. Histopathological examination revealed that compound feed consumption induced looser liver cell arrangement, hepatocyte morphological irregularities, and vacuolization. A total of 1033 and 1428 differentially expressed genes (DEGs), and 187 and 184 differential metabolites (DMs), were identified in the C vs. L and C vs. M groups, respectively. Transcriptomic analysis revealed that the significantly and commonly enriched metabolic pathways shared by both comparison groups were predominantly involved in amino acid, carbohydrate, and lipid metabolisms. Metabolomic analysis demonstrated that the significantly and commonly enriched metabolic pathways shared by both comparison groups were the arachidonic acid metabolism, linoleic acid metabolism, oxidative phosphorylation, and PPAR signalling pathways. Integrated omics analysis showed that the PPAR signalling pathway was the only significantly co-enriched pathway across both omics datasets. This study provides new insights into the molecular mechanisms of compound feed adaptation and provides theoretical support for selecting feed traits in S. chuatsi. Full article

Papillomaviruses (PVs) are double-stranded DNA viruses known to induce a variety of epithelial lesions in dogs, ranging from benign hyperplasia to malignancies. In regions of rich biodiversity such as the Western Amazon, data on the circulation and genetic composition of canine papillomaviruses (CPVs) remain scarce. This study investigated CPV types present in oral and cutaneous papillomatous lesions in domiciled dogs from Acre and Rondônia States, Brazil. Sixty-one dogs with macroscopically consistent lesions were clinically evaluated, and tissue samples were collected for histopathological examination and PCR targeting the L1 gene. Among these, 37% were histologically diagnosed as squamous papillomas or fibropapillomas, and 49.2% (30/61) tested positive for papillomavirus DNA. Sequencing of the L1 gene revealed that most positive samples belonged to CPV1 (Lambdapapillomavirus 2), while one case was identified as CPV8 (Chipapillomavirus 3). Complete genomes of three CPV1 strains were obtained via high-throughput sequencing and showed high identity with CPV1 strains from other Brazilian regions. Phylogenetic analysis confirmed close genetic relationships among isolates across distinct geographic areas. These findings demonstrate the circulation of genetically conserved CPVs in the Amazon and reinforce the value of molecular and histopathological approaches for the accurate diagnosis and surveillance of viral diseases in domestic dogs, especially in ecologically complex regions. Full article

Introduction: Although lipomas are common benign tumors found in adults, lipomas of the bladder are extremely rare. Bladder lipomas are infrequently reported in the urologic literature, with only 19 cases published worldwide. These can present as a mass on cystoscopy and cause irritative voiding symptoms, depending on their location. Upon transurethral resection, seeing fat can be concerning for a perforation, as lipoma can be mistaken for extravesical fat. Hence, familiarity with this rare entity is of paramount importance for urologists to prevent unnecessary investigations and interventions that are needed in case of a true bladder perforation. Case presentation: This study presents a case of bladder lipoma in a 73-year-old male with end-stage renal disease who presented for pretransplant urologic evaluation due to microscopic hematuria and irritative lower urinary tract symptoms (LUTS). During cystoscopy, a bladder mass was seen, and a transurethral resection of the bladder tumor (TURBT) revealed bright yellow adipose tissue immediately underneath the bladder mucosa. Concerns about perforation were obviated when seeing intact detrusor muscle underneath, visually confirming the integrity of the bladder wall. The resection was completed, and the CT scan was re-read with the radiologist, which confirmed the presence of a lipoma that was missed pre-operatively due to patient’s oliguria and collapsed bladder. No catheter drainage or cystogram was performed based on these findings. Outcome: The patient healed without any complications. Histopathology confirmed the diagnosis of a mature lipoma. The patient was cleared for transplant from a urologic standpoint and had a successful renal transplantation without delay. Discussion: This case documents the anomalous occurrence of a lipoma within the bladder and supports maintaining a broad differential, including liposarcoma, angiomyolipoma, and other non-malignant fatty tumors during the evaluation of a bladder mass. Full article

Hydrogen-rich water (HRW) has shown neuroprotective effects in acute brain injury, but its role in chronic radiation-induced brain injury (RIBI) remains unclear. This study investigated the long-term efficacy of HRW in mitigating cognitive impairment and neuronal damage caused by chronic RIBI. Fifty male Sprague Dawley rats were randomly divided into five groups: control, irradiation (IR), IR with memantine, IR with HRW, and IR with combined treatment. All but the control group received 20 Gy whole-brain X-ray irradiation, followed by daily interventions for 60 days. Behavioral assessments, histopathological analyses, oxidative stress measurements, ¹⁸F-FDG PET/CT imaging, transcriptomic sequencing, RT-qPCR, Western blot, and serum ELISA were performed. HRW significantly improved anxiety-like behavior, memory, and learning performance compared to the IR group. Histological results revealed that HRW reduced neuronal swelling, degeneration, and loss and enhanced dendritic spine density and neurogenesis. PET/CT imaging showed increased hippocampal glucose uptake in the IR group, which was alleviated by HRW treatment. Transcriptomic and molecular analyses indicated that HRW modulated key genes and proteins, including CD44, CD74, SPP1, and Wnt1, potentially through the MIF, Wnt, and SPP1 signaling pathways. Serum CD44 levels were also lower in treated rats, suggesting its potential as a biomarker for chronic RIBI. These findings demonstrate that HRW can alleviate chronic RIBI by preserving neuronal structure, reducing inflammation, and enhancing neuroplasticity, supporting its potential as a therapeutic strategy for radiation-induced cognitive impairment. Full article

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. Full article

(1) Background: Epidemiological studies link ozone (O₃) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O₃ were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O₃ exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O₃-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O₃ triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article

Background: Pigmented superficial skin lesions pose a persistent diagnostic challenge due to overlapping clinical and dermoscopic appearances between benign and malignant entities. While histopathology remains the gold standard, there is growing interest in non-invasive imaging models that can preoperatively stratify malignancy risk. This methodological pilot study was designed to explore the feasibility and initial diagnostic performance of a novel radiology-adapted logistic regression approach. To develop and preliminarily evaluate a new logistic model integrating both structural (lesion size, depth) and vascular (Doppler patterns) ultrasonographic features for non-invasive risk stratification of pigmented superficial skin lesions. Material and Methods: In this prospective single-center pilot investigation, 44 patients underwent standardized high-frequency grayscale and Doppler ultrasound prior to excisional biopsy. Lesion size, depth, and vascularity patterns were systematically recorded. Three logistic regression models were constructed: (1) based on lesion size and depth, (2) based on vascularity patterns alone, and (3) combining all parameters. Model performance was assessed via ROC curve analysis. Intra-observer reliability was determined by repeated measurements on a random subset. Results: The lesion size and depth model yielded an AUC of 0.79, underscoring the role of structural features. The vascularity-only model showed an AUC of 0.76. The combined model demonstrated superior discriminative ability, with an AUC of approximately 0.85. Intra-observer analysis confirmed excellent repeatability (κ > 0.80; ICC > 0.85). Conclusions: This pilot study introduces a novel logistic framework that combines grayscale and Doppler ultrasound parameters to enhance non-invasive malignancy risk assessment in pigmented superficial skin lesions. These encouraging initial results warrant larger multicenter studies to validate and refine this promising approach. Full article

Background/Objectives: Chronic inflammation and Western-style diets elevate colorectal cancer (CRC) risk, particularly in individuals with colitis, a feature of inflammatory bowel disease (IBD). Diets rich in polyphenol-containing functional foods, such as cocoa, may reduce gut inflammation and modulate the gut microbiome. This study investigated the impact of cocoa polyphenol (CP) supplementation on inflammation and microbiome composition in mice with colitis, fed either a healthy or Western diet, before, during, and after the onset of disease. We hypothesized that CPs would attenuate inflammation and promote distinct shifts in the microbiome, especially in the context of a Western diet. Methods: A 2 × 2 factorial design tested the effects of the basal diet (AIN93G vs. total Western diet [TWD]) and CP supplementation (2.6% w/w CocoaVia™ Cardio Health Powder). Inflammation was induced using the AOM/DSS model of colitis. Results: CP supplementation did not reduce the severity of colitis, as measured by disease activity index or histopathology. CPs did not alter gene expression in healthy tissue or suppress the colitis-associated pro-inflammatory transcriptional profile in either of the two diet groups. However, fecal microbiome composition shifted significantly with CPs before colitis induction, with persistent effects on several rare taxa during colitis and recovery. Conclusions: CP supplementation did not mitigate inflammation or mucosal injury at the tissue level, nor did it affect the expression of immune-related genes. While CPs altered microbiome composition, most notably in healthy mice before colitis, these shifts did not correspond to changes in inflammatory signaling. Basal diet remained the primary determinant of inflammation, mucosal damage, and colitis severity in this model. Full article

Background: Spinal muscular atrophy type 1 (SMA1) is a severe neuromuscular disorder characterized by progressive muscle weakness and atrophy, including the muscles of the oral cavity and esophagus. Eosinophilic esophagitis (EoE), a chronic, allergic disease, presents with eosinophilic infiltration of the esophagus, leading to esophageal dysmotility. Feeding difficulties may occur in both conditions. So far, the coexistence of EoE and SMA1 has not been described; we present the first such case. Case presentation: The patient was a girl with SMA1 diagnosed shortly after birth, treated with nusinersen and onasemnogene abeparvovec, and fed a standard industrial diet through a gastrostomy. In her second year of life, she developed increasing symptoms: distress during feeding, regurgitation, vomiting, and weight loss. She was treated with proton pump inhibitors without clinical improvement. Gastroscopy was performed, revealing superficial epithelial damage with bleeding in the proximal esophagus. Histopathology showed chronic inflammation with up to 150 eosinophils per high-power field, microabscesses, spongiosis, and basal layer hypertrophy. The girl was diagnosed with EoE. Her diet was switched from a standard industrial formula to an amino acid-based formula, which led to marked clinical improvement, the resolution of symptoms, and appropriate weight gain. Conclusions: This case report highlights the challenges of diagnosing EoE in SMA1 patients and emphasizes the need for multidisciplinary approaches and further investigation of allergic manifestations in SMA1 patients. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Diabetic wounds are a devastating complication that cause chronic pain, recurrent infections, and limb amputations due to impaired healing. Despite advances in wound care, existing therapies often fail to address the underlying molecular dysregulation, highlighting the need for innovative and safe therapeutic approaches. Among these, D-amino acids such as D-tryptophan (D-Trp) have emerged as key regulators of cellular processes; however, their therapeutic potential in diabetic wounds remains largely unexplored. Here, we investigate the therapeutic potential of D-Trp in streptozotocin (STZ)-induced diabetic mice, comparing it with phosphate-buffered saline (PBS) controls and vascular endothelial growth factor (VEGF) as a positive control. Wound healing, inflammation, and histopathology were assessed. Protein and gene expression were analyzed via Western blot and RT-qPCR, respectively. Biolayer interferometry (BLI) measured the binding of D-Trp to hypoxia-inducible factor-1α (HIF-1α). D-Trp accelerated wound healing by modulating extracellular matrix (ECM) remodeling, signaling, and apoptosis. It upregulated matrix metalloproteinases (MMP1, MMP3, MMP-9), Janus kinase 2 (JAK2), and mitogen-activated protein kinase (MAPK) proteins while reducing pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6). D-Trp also suppressed caspase-3 and enhanced angiogenesis through HIF-1α activation. These findings suggest that D-Trp promotes healing by boosting ECM turnover, reducing inflammation, and activating MAPK/JAK pathways. Thus, D-Trp is a promising therapeutic for diabetic wounds. Full article

The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The present study investigates the pharmacological properties of Bothrops atrox venom (VBA), focusing specifically on its impact on renal blood flow. Following the renal perfusion procedure, kidney tissues were processed for histopathological examination. Statistical analysis of all evaluated parameters was conducted using ANOVA and Student’s t-test, with significance set at p < 0.005. Administration of VBA resulted in a marked reduction in both perfusion pressure and renal vascular resistance. In contrast, there was a significant elevation in urinary output and glomerular filtration rate. Histological changes observed in the perfused kidneys were mild. The involvement of nitric oxide in the pressor effects of Bothrops atrox venom was not investigated in renal perfusion systems or in in vivo models. Treatment with VBA led to elevated nitrite levels in the bloodstream of the experimental animals. This effect was completely inhibited following pharmacological blockade with L-NAME. Based on these findings, we conclude that VBA alters renal function and promotes increased nitric oxide production. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article

Retinal degeneration is associated with dietary factors and environmental light exposure. This study investigated the effects of a high-fructose high-fat (HFHF) diet on susceptibility to blue light (BL)-induced retinal damage. Male ICR mice were randomized into three groups: control, BL alone, and BL plus HFHF diet (BL + HFHF). The BL + HFHF group consumed the HFHF diet for 40 weeks, followed by 8 weeks of low-intensity BL exposure (465 nm, 37.7 lux, 0.8 μW/cm²) for 6 h daily. The BL group underwent the same BL exposure while kept on a standard diet. Histopathological analysis showed that, under BL exposure, the HFHF diet significantly reduced the number of photoreceptor nuclei and the thickness of the outer nuclear layer and inner/outer segments compared to the BL group (p < 0.05). While BL exposure alone caused oxidative DNA damage, rhodopsin loss, and Müller cell activation, the combination with an HFHF diet significantly amplified the oxidative DNA damage and Müller cell activation. Moreover, the HFHF diet increased blood–retinal barrier permeability and triggered apoptosis under BL exposure. Mechanistically, the BL + HFHF group exhibited increased retinal advanced glycated end product (AGE) deposition, accompanied by the activation of the receptor for AGE (RAGE), NFκB, and the NLRP3 inflammasome-dependent IL-1β pathway. In conclusion, this study underscores that unhealthy dietary factors, particularly those high in fructose and fat, may intensify the hazard of BL and adversely impact visual health. Full article