Search Results (952)

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

Due to the stroke-protective effects of dietary fiber and anthocyanin together with the synergistic interaction, we hypothesized that the functional drink containing the anthocyanins and dietary fiber-enriched functional ingredient from banana and germinated black Jasmine rice (BR) should protect against ischemic stroke. BR at doses of 300, 600, and 900 mg/kg body weight (BW) was orally given to male Wistar rats weighing 290–350 g once daily for 21 days, and they were subjected to ischemic reperfusion injury induced by temporary occlusion of the middle cerebral artery (MCAO/IR) for 90 min. The treatment was prolonged for 21 days after MCAO/IR. They were assessed for brain infarction volume, neuron density, Nrf2, MDA, and catalase in the cortex together with serum TNF-α and IL-6. Lactobacillus and Bifidobacterium spp. in feces were also assessed. Our results showed that BR improved the increase in brain infarcted volume, MDA, TNF-α, and IL-6 and the decrease in neuron density, Nrf2, catalase, and both bacteria spp. induced by MCAO/IR. These data suggest the stroke-protective effect of the novel functional drink, and the action may involve the improvement of Nrf2, oxidative stress, inflammation, and the amount of Lactobacillus and Bifidobacterium spp. Full article

Background: Midfacial fractures are common outcomes of facial trauma. While younger individuals typically sustain these injuries through high-energy events like assaults and traffic or sports accidents, elderly patients increasingly present with fractures from low-energy mechanisms, primarily falls. Purpose: The aim of this study was to analyze age- and gender-specific patterns in midfacial fractures over a 10-year period, with emphasis on elderly individuals and low-energy trauma. Methods: A retrospective review was performed of proven midfacial fractures between 2013 and 2022 at the Department of Oral and Maxillofacial Surgery (University of Pécs, Hungary). The patients were stratified by age (<65 vs. ≥65 years) and gender. The variables included the injury mechanism, fracture localization, the dental status, hospitalization, and the presence of associated injuries. Bivariate analyses were performed, and the significance level was set to p < 0.05. Results: A total of 957 radiologically confirmed midfacial fracture cases were evaluated, of whom 344 (35.9%) were ≥65 years old. In the elderly group, females had a 19-fold higher risk for midfacial trauma than younger females (OR: 19.1, 95%CI: 9.30–39.21). In the older group, a fall was significantly the most frequent injury mechanism (OR: 14.5; 95%CI: 9.9–21.3), responsible for 89.5% of the cases, while hospitalization (OR: 0.36; 95%CI: 0.23–0.56) was less characteristic. Most of the fractures occurred in the zygomatic bone, in the zygomaticomaxillary complex, or in the anterior wall of the maxilla. Associated injuries in the elderly group included mostly lower limb injuries—particularly pertrochanteric femoral fractures in females—and upper limb injuries, with a slight male dominance. Conclusions: Low-energy falls are the primary cause of midfacial fractures in elderly patients, particularly in women. Tailored prevention and management strategies are essential for improving the outcomes in this growing demographic group. Full article

Background/Objectives: This study investigates the therapeutic potential of camel milk-derived extracellular vesicles (CM-EVs) for treating colonic damage caused by high-altitude hypoxia, supporting the WHO’s “Food as Medicine” initiative. Methods: Using a 5500 m mouse model, researchers induced colonic injury and treated it with oral CM-EVs for 15 days, comparing results to whole camel milk. Results: CM-EVs outperformed whole milk, significantly improving colon health by restoring barrier integrity and reducing disease activity index (DAI) (p < 0.01). They boosted beneficial bacteria like Lactobacillus and Bifidobacterium and decreased Enterobacteriaceae (p < 0.01). Metabolic analysis showed restored bile acid balance and amino acid modulation via the FXR/NF-κB pathway, reducing TLR4/MyD88-mediated inflammation and oxidative stress (p < 0.01). Fecal microbiota transplantation in the CM-EVs group notably decreased DAI and increased colon length (p < 0.05). Conclusions: CM-EVs repair mucosal damage, balance microbiota, and regulate metabolism to combat hypoxia-induced colonic damage, suggesting their potential as nutraceuticals and altitude-adaptive foods. This showcases nanotechnology’s role in enhancing traditional dietary benefits via precision nutrition. Full article

Perfluorooctanoic acid (PFOA) and its replacement, GenX, are per- and polyfluoroalkyl substances (PFASs) widely used in industrial and consumer applications. Pregnant women are a vulnerable population to environmental pollutants. The maternal effects of GenX and PFOA exposure during pregnancy have not been fully elucidated. In this study, pregnant mice received daily oral doses of GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water (control) throughout gestation. Histopathological analyses revealed significant liver abnormalities in both exposure groups, including hepatocyte swelling, cellular disarray, eosinophilic degeneration, karyopyknosis, lipid vacuolation, and increased inflammatory responses. Through transcriptomics analyses, it was found that multiple metabolic and inflammatory pathways were enriched in both exposure groups. In the GenX group, overexpression of CYP4A, c-Myc, and Oatp2 proteins and decreased expression of EGFR and β-catenin in the liver suggested disruption of lipid and bile acid metabolism. In the PFOA group, significantly upregulated protein levels of NLRP3, GSDMD, caspase-1, IL-18, and IL-1β indicated hepatic pyroptosis. Despite these distinct pathways, both compounds triggered inflammatory cytokine release in the liver, consistent with the results of the transcriptomics analysis, suggesting shared mechanisms of inflammatory liver injury. Taken together, our findings provided novel insights into the hepatotoxicity mechanisms of GenX and PFOA exposure during pregnancy, underscoring the potential health risks associated with PFAS exposure. Full article

Background: Malnutrition is associated with adverse clinical and economic outcomes. We recently reported that the hospital mortality rate in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected inpatients was higher in malnourished patients than in those without malnutrition. The present study aimed to determine if SARS-CoV-2-infected inpatients who received oral nutrition supplementation (ONS) had improved survival. We performed a retrospective cohort study including 37,215 adults (aged 18 and older) admitted with COVID-19 to five Johns Hopkins–affiliated hospitals between 1 March 2020, and 31 March 2023. Malnutrition risk was initially screened using the Malnutrition Universal Screening Tool (MUST), with cases subsequently confirmed by registered dietitians via a standardized, validated assessment protocol. Logistic regression analysis predicting hospital mortality examined the association of ONS with hospital survival in SARS-CoV-2-infected inpatients, incorporating covariates and weights for ONS receipt. Results: Malnutrition was an independent predictor of higher hospital mortality from COVID-19 illness. The prevalence of malnutrition among adult inpatients with SARS-CoV-2 infection in our cohort was 15.22%. Inpatient adults with moderate or severe malnutrition in the context of acute illness or injury who were given ONS had lower odds of inpatient mortality (moderate OR = 0.72, 95% CI 0.62–0.85; severe OR = 0.76, 95% CI 0.67–0.87; both p < 0.001). Overweight and obese patients who received ONS had higher odds of inpatient mortality (overweight OR = 1.15, 95% CI 1.08–1.22, p < 0.0001; obese OR = 1.08, 95% CI 1.01–1.14, p = 0.02, respectively). For inpatients who were underweight, receiving ONS was protective against inpatient mortality (OR = 0.78, 95% CI 0.68–0.88, p = 0.0001). Thus, among adult inpatients with SARS-CoV-2 infection, malnourished and underweight individuals appeared to experience improved survival when provided with oral nutritional supplements (ONS), whereas overweight or obese patients remain at an elevated risk of mortality. The timing of ONS receipt in hospitalized patients with SARS-CoV-2 influenced mortality. Patients who had earlier time to ONS had 13% lower odds of inpatient mortality (OR = 0.87, 95% CI 0.79–0.97, p = 0.0105). Conclusions: In a cohort of SARS-CoV-2 adult inpatients, those with confirmed malnutrition receiving oral nutrition supplements had a higher likelihood of hospital survival. This is the first study demonstrating an association of oral nutrition intervention with reduced hospital mortality in malnourished SARS-CoV-2-infected adults. Full article

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article

Background/Objectives: Obesity is increasingly recognized as a global health concern due to its association with metabolic disorders and gut microbiota dysbiosis. While probiotics offer promise in regulating gut microbiota and improving host metabolism, strain-specific effects remain underexplored, particularly for canine-derived probiotics. This study aimed to isolate and characterize a novel probiotic strain, Ligilactobacillus animalis LA-1, and evaluate its anti-obesity effects and underlying mechanisms using a high-fat diet (HFD)-induced obese mouse model. Methods: LA-1 was isolated from the feces of a healthy dog and assessed for probiotic potential in vitro, including gastrointestinal tolerance, bile salt hydrolase activity, cholesterol-lowering capacity, and fatty acid absorption. Male C57BL/6J mice were fed either a standard chow diet or an HFD for 16 weeks, with HFD mice receiving oral LA-1 supplementation (2 × 10⁹ CFU/day). Multi-omics analyses, including 16S rRNA gene sequencing, short-chain fatty acid (SCFA) quantification, and untargeted liver metabolomics, were employed to investigate the effects of LA-1 on gut microbiota composition, metabolic pathways, and obesity-related phenotypes. Results: LA-1 supplementation significantly alleviated HFD-induced weight gain, hepatic lipid accumulation, and adipose tissue hypertrophy, without affecting food intake. It improved serum lipid profiles, reduced liver injury markers, and partially restored gut microbiota composition, decreasing the Firmicutes/Bacteroidetes ratio and enriching SCFA-producing genera. Total SCFA levels, particularly acetate, propionate, and butyrate, increased following LA-1 treatment. Liver metabolomics revealed that LA-1 modulated pathways involved in lipid and amino acid metabolism, resulting in decreased levels of acetyl-CoA, triglycerides, and bile acids. Conclusions: L. animalis LA-1 exerts anti-obesity effects via gut microbiota modulation, enhanced SCFA production, and hepatic metabolic reprogramming. These findings highlight its potential as a targeted probiotic intervention for obesity and metabolic disorders. Full article

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury (DILI) globally, which necessitates effective therapies. Gallic acid (GA), a naturally abundant polyphenol, possesses potent antioxidant and anti-inflammatory properties that may overcome the limitations of N-acetylcysteine (NAC), such as its narrow therapeutic window. This study systematically investigated the hepatoprotective effects and underlying molecular mechanisms of GA against APAP-induced acute liver injury (ALI). Mice received an intraperitoneal injection of APAP (300 mg/kg), followed by an oral administration of GA (50 or 100 mg/kg) or NAC (150 mg/kg) 1 h post-intoxication. Both GA and NAC significantly ameliorated hypertrophy and histopathological damage, as evidenced by reduced serum ALT/AST levels and inflammatory cytokines. TUNEL staining revealed a marked suppression of apoptotic and necrotic cell death, further supported by the downregulation of pro-apoptotic Bax and the upregulation of anti-apoptotic Bcl-2 mRNA expression. GA and NAC treatment restored hepatic glutathione (GSH) content, enhanced antioxidant enzyme gene expression, and reduced malondialdehyde (MDA) accumulation. Mechanistically, GA and NAC inhibited MAPK phosphorylation while activating AMPK signaling. Taken together, these findings demonstrate that GA mitigates APAP-induced ALI by modulating oxidative stress and inflammation through the regulation of MAPK/AMPK signaling proteins. Full article

Background: Acute lung injury (ALI) is driven by inflammatory cascades and reactive oxygen species (ROS) generation, with the progression to severe cases markedly increasing mortality. Sinapine thiocyanate (ST), a bioactive natural compound isolated from Sinapis Semen Albae (SSA), demonstrates both anti-inflammatory and antioxidant pharmacological activities. However, no monotherapeutic formulation of ST has been developed to date. A dry powder inhaler (DPI) enables targeted pulmonary drug delivery with excellent stability profiles and high inhalation efficiency. Methods: ST was purified and prepared as inhalable dry powder particles via an antisolvent crystallization technique. The therapeutic mechanisms of ST against ALI were elucidated by network pharmacology and pharmacokinetic analyses, with the therapeutic efficacy of the ST DPI in ALI mitigation being validated using LPS-induced rat models. Results: The ST DPI showed ideal aerodynamic characteristics. Notably, ST exhibited a three-compartment (triexponential) pharmacokinetic profile following both intravenous tail vein injection and inhalation administration. Furthermore, the inhaled formulation displayed a prolonged systemic residence time, which confers therapeutic advantages for pulmonary disease management. Furthermore, the inhalation administration of ST demonstrated a 2.7-fold increase in AUC compared with oral gavage, with a corresponding enhancement in systemic exposure. The ST DPI formulation demonstrated significant therapeutic efficacy against ALI in rats by downregulating inflammatory cytokines and modulating oxidative stress levels, mechanistically achieved through the MAPK-mediated regulation of cellular apoptosis via a positive feedback loop. Conclusions: The unique triexponential plasma level profiles of an ST DPI provide a promising pharmacokinetics-based therapeutic strategy for ALI, leveraging its marked efficacy in attenuating inflammation, oxidative stress, and pulmonary injury. Full article

Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach. Full article

Background: Facial trauma is one of the few surgical conditions that is routinely managed by three distinct disciplines, including Oral and Maxillofacial Surgery (OMS), Plastic and Reconstructive Surgery (PRS), and Otolaryngology (ENT). This study aims to evaluate mandibular trauma management strategies and clinical outcomes among three operating services. Methods: An IRB-approved, retrospective chart review was performed over a ten-year period (2007–2016) at a major, urban, Level I trauma center for all patients treated for an isolated mandibular injury determined by ICD-9 codes. Of the 2299 patients evaluated for traumatic facial injuries, 191 met the inclusion criteria and 137 had longitudinal data. Patient, fracture, and management characteristics and clinical outcomes were compared among three surgical services. Results: Most patients were male (95.3%), and assaults were the most common etiology of injury (79.1%). The angle/ramus was the most common single location (31.4%), and 47.6% of patients had multiple fractures. There was a statistically significant difference between specialties when assessing the use of operative versus non-operative approaches to fracture management (p < 0.001), and within operative management, for the use of open reduction-internal fixation (ORIF) alone versus ORIF with maxillomandibular fixation (MMF) (p = 0.002). There was no significant difference in the overall complications between specialties (p = 0.227). Conclusions: Services differ in their decision to pursue operative versus non-operative management, as well as the decision for postoperative MMF, though these differences in decision-making were not associated with a significant difference in the overall complications. Full article

Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp stem cells (DPSCs) and their derivatives, including extracellular vesicles, conditioned medium, and intracellular factors, in accelerating skin wound healing. The key mechanisms include: (1) DPSCs regulating inflammatory microenvironments by promoting anti-inflammatory M2 macrophage polarization; (2) DPSCs activating vascular endothelial growth factor (VEGF) to drive angiogenesis; (3) DPSCs optimizing extracellular matrix (ECM) spatial structure through matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) balance; and (4) DPSCs enhancing transforming growth factor-β (TGF-β) secretion to accelerate granulation tissue formation. Collectively, these processes promote wound healing. In addition, we explored potential factors that accelerate wound healing in DPSCs, such as oxidative stress, mechanical stimulation, hypertension, electrical stimulation, and organoid modeling. In addition to demonstrating the great potential of DPSCs for skin repair, this review explores their translational prospects in mucosal regenerative medicine. It covers the oral cavity, esophagus, colon, and fallopian tube. Some studies have found that combining DPSCs and their derivatives with drugs can significantly enhance their biological effects. By integrating insights from skin and mucosal models, this review offers novel ideas and strategies for treating chronic wounds, inflammatory bowel disease, and mucosal injuries. It also lays the foundation for connecting basic research results with clinical practice. This represents a significant step forward in tackling these complex medical challenges and lays a solid scientific foundation for developing more targeted and efficient regenerative therapies. Full article

Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these mechanisms. Methods: A narrative synthesis of peer reviewed literature from 2021 to 2025 on spike related injury and vaccine adverse events was conducted, supplemented by clinical case series and mechanistic observations from long COVID. The findings were arranged into a four stage therapeutic sequence ordered by pathophysiological precedence. Results: Stage one aims to reopen hypoperfused tissue through oral fibrinolytics that degrade fibrin amyloid resistant microclots; stage two intends to neutralise circulating or tissue bound spike via a receptor binding domain monoclonal antibody cocktail; stage three seeks to eliminate reactivated viral or microbial reservoirs with targeted antivirals or antimicrobials once perfusion is improved; and stage four aspires to support tissue repair with mitochondrial supplements and, when indicated, cell based therapies. Omitting or reordering stages may reduce efficacy or foster resistance. Conclusions: This hypothesis driven framework outlines a biologically plausible roadmap for longvax research. By matching interventions to specific mechanisms (fibrinolysis, spike neutralisation, pathogen clearance and regeneration), it aims to guide controlled trials and compassionate pilot programs directed at durable recovery rather than chronic symptom management. Full article

Background: Traumatic brain injury (TBI) is a leading cause of mortality and disability, particularly in patients on anticoagulation therapy. While anticoagulants are linked to higher TBI mortality, the specific impact of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) on severe TBI (sTBI) outcomes remains unclear, especially in light of newer reversal agents. Therefore, this study evaluates long-term mortality and complication risks associated with pre-injury use of DOACs and VKAs in sTBI patients from a large, real-world cohort. Methods: A retrospective cohort study was conducted using the TriNetX global research network, identifying patients with sTBI between 2016 and 2022. Patients were grouped based on pre-injury anticoagulant use: DOAC, VKA, or none. Propensity score matching was performed, adjusting for age, comorbidities, and baseline characteristics. The primary outcome was all-cause mortality at 1-, 3-, 6-, and 12-months post-injury. Secondary outcomes included hospital and surgical complications up to 30 days post-injury. Results: A total of 40,563 patients met the inclusion criteria. At all time intervals, no significant mortality differences were found between the PSM-matched groups. Conclusions: In patients with sTBI, pre-injury DOAC or VKA use was not associated with increased short- or long-term mortality. These findings suggest that, with current perioperative practices, anticoagulation can be managed without adversely affecting outcomes. Full article