Protective effect of wild Corni fructus methanolic extract against acute alcoholic liver injury in mice

Background: In Chinese folk medicine, Corni fructus (C. fructus) has traditionally been used to improve liver function, although the mechanism underlying its activity remains unclear. The aim of the present study was to evaluate the protective effects of wild C. fructus methanolic extract against acute alcoholic liver injury.Methods: Alcohol was administered to mice for three consecutive days, either alone or in combination with C. fructus methanolic extract (50, 100, or 200mg/kg body weight/d). Serum and liver tissue were collected from the animals and subjected to biochemical and histopathological analyses.Results:C. fructus significantly alleviated alcohol-induced liver injury by reducing serum alanine aminotransferase, aspartate aminotransferase, and thiobarbituric acid reactive species, inhibiting hydroxyl radicals (center dot OH), and increasing total superoxide dismutase, glutathione peroxidase, and glutathione in the liver (P<0.05). In addition, the C. fructus treatment inhibited the expression and activity of cytochrome P450 2E1 (P<0.05)Conclusions:C. fructus could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury.- This work was supported by the Construction Project of Shaanxi Collaborative Innovation Center (2015, Shaanxi Sci-tech University); High-End Foreign Experts Recruitment Program [Grant GDW20146100228]; and Key Construction Program of International Cooperation Base in S&T Shaanxi Province, China [Grant 2015SD0018].info:eu-repo/semantics/publishedVersio

Evaluation of the RIFER procedure in treating high intersphincteric anal fistulas

IntroductionA high intersphincteric anal fistula is a common anorectal disease that is challenging to treat due to high recurrence rates and has the risk of sphincter damage, which can lead to incontinence. This study aimed to evaluate the efficacy and safety of the rectal incision, fistula excision, and reconstruction (RIFER) procedure for treating high intersphincteric anal fistulas.MethodsTwenty-six patients with high intersphincteric anal fistulas who were admitted to Nanjing Hospital of Traditional Chinese Medicine between September 2021 and March 2024 and underwent the RIFER procedure were included. Patients were followed up for 6 months, and treatment efficacy, recurrence, and postoperative complications after the RIFER procedure were assessed.ResultsThe surgical cure rate of patients treated with RIFER was 100%, with no recurrence or postoperative complications during the follow-up period. The average wound-healing time was 45.40 days. Functional scoring indicators, such as the visual analog and Wexner anal function scores, improved at different postoperative time points. After the RIFER procedure, the incision scar score of most patients (18 of 25) was 0, and none of the patients reported keyhole-like anal deformities. The mean hospital stay was 10.15 days.ConclusionThe RIFER procedure demonstrated remarkable efficacy and safety in the treatment of high intersphincteric anal fistulas, with no recurrence or postoperative complications. This procedure is suitable for treating high intersphincteric anal fistulas in clinical practice

The blood parameters and liver function changed inconsistently among children between burns and traumatic injuries

Objective Burn and traumatic injury are two kinds of injury by modality. They cause acute phase response and lead to a series of pathological and physiological changes. In this study, we explored whether there are differences in routine blood parameters and liver enzyme levels between burned and traumatically injured children. Methods Patients under 18 years old with injuries were recruited. Their demographic and clinical data were recorded. Collected clinical data included routine blood parameters (white blood cell count (WBC), red blood cell count (RBC), platelets (PLT), hemoglobin (HB)), serological enzyme levels (alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyltransferase (GGT), alkaline phosphatase (ALP), cholinesterase (CHE)), and total protein (TP) levels (albumin (ALB), globulin (GLB)). A generalized linear model and multivariate analysis of variance were used to conduct comparisons. Results A total of 162 children (109 with burns and 53 with traumatic injuries) with a mean age of 4.36 ± 4.29 years were enrolled in the study. Burned children had higher levels of RBC, HB, WBC, AST and lower levels of TP, CHE, ALB than traumatically injured children (P < 0.05). Moreover, the concentration of WBC and HB was higher in males compared to females (P < 0.001). Conversely, the level of AST and TP in males was lower, AST levels were significantly lower in males (P = 0.005). Age positively correlated with the levels of HB, AST and TP (P < 0.001), and negatively correlated with WBC (P < 0.001). With decreasing body mass index (BMI), the levels of WBC, HB, AST and TP significantly increased in both groups of injured children (P < 0.001). In addition, ISS was positively correlated with WBC and HB levels (P < 0.001), but negatively correlated with AST and TP levels (P < 0.001). Conclusions Children with burn injuries suffered a greater acute response and liver damage than traumatically injured children. This may in part underlie clinical observations of differences in children morbidity and mortality in response to different injury types

Preventive hyperbaric oxygen therapy improves acute graft-versus-host disease by activating the Nrf2/HO-1 pathway

BackgroundHyperbaric oxygen therapy (HBOT) has been confirmed as an effective and economical therapeutic modality for treating hemorrhagic cystitis (HC), whether induced by infection or acute graft-versus-host disease (aGVHD), in transplant recipients. However, its potential benefits in treating aGVHD remain largely unknown. This study explored the effects of HBOT on aGVHD and its underlying mechanisms.MethodsThe beneficial effects of HBOT on aGVHD were investigated in a murine model. Manifestations, pathological alterations, reactive oxygen species (ROS) levels in target organs, and survival data of the recipient mice were collected. Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and its downstream enzyme heme-oxygenase 1 (HO-1) expression in mouse samples were assessed via Western blot and immunohistochemistry analyses. ML385, an Nrf2 inhibitor, was used to validate the protective role of Nrf2 in the beneficial effect of HBOT on aGVHD. Furthermore, we initiated a clinical cohort study and collected data from the patients with definite aGVHD before and after HBOT to validate the preclinical conclusions.ResultsWe found that HBOT alleviated aGVHD in mice, which was associated with a significantly prolonged overall survival (OS) and reduced pathological injury, whereas Nrf2 inhibition had the opposite effect. HBOT decreased ROS levels and proinflammatory cytokines, including IL-6 and TNF-α, while upregulated Nrf2 and its downstream antioxidant enzyme HO-1. In the clinical cohort study, the incidence of grades 1–3 aGVHD was significantly lower in the combination arm containing HBOT than in the HBOT-free cohort.ConclusionPreventive HBOT can mitigate aGVHD by activating the Nrf2/HO-1 signal transduction pathway, suggesting that HBOT may be a feasible approach for both the prevention and treatment of aGVHD.Clinical trial registrationClinicalTrials.gov, identifier NCT04502628

Steam explosion pretreatment enhancing enzymatic digestibility of overground tubers of tiger nut (Cyperus esculentus L.)

IntroductionTiger nut (TN) is recognized as a high potential plant which can grow in well-drained sandy or loamy soils and provide food nutrients. However, the overground tubers of TN remain unutilized currently, which limits the value-added utilization and large-area cultivation of this plant.MethodsIn the present study, the overground tubers of TN were subjected to enzymatic hydrolysis to produce fermentable sugars for biofuels production. Steam explosion (SE) was applied to modify the physical-chemical properties of the overground tubers of TN for enhancing its saccharification.Results and discussionResults showed that SE broke the linkages of hemicellulose and lignin in the TN substrates and increased cellulose content through removal of hemicellulose. Meanwhile, SE cleaved inner linkages within cellulose molecules, reducing the degree of polymerization by 32.13–77.84%. Cellulose accessibility was significantly improved after SE, which was revealed visibly by the confocal laser scanning microscopy imaging techniques. As a result, enzymatic digestibility of the overground tubers of TN was dramatically enhanced. The cellulose conversion of the SE treated TN substrates reached 38.18–63.97%, which was 2.5–4.2 times higher than that without a SE treatment.ConclusionTherefore, SE pretreatment promoted saccharification of the overground tubers of TN, which paves the way for value-added valorization of the TN plants

A de novo mutation in RAB11A is associated with neurodevelopmental disorder accompanied by variable multisystem abnormalities

IntroductionRAB11A, a Rab GTPase, is crucial for intracellular transport and recycling. Recently, RAB11A mutations have been found to be associated with neurodevelopmental disorders in cohorts. At present, there are still no effective treatment methods for NDDs caused by RAB11A deficiency, thus, identifying pathogenic mutations and generating disease models is crucial for advancing our understanding of these conditions.MethodsWe analyzed the clinical presentation of a 4-year and 4-month-old boy with a de novo RAB11A mutation c.370A&gt;G. To examine the consequences of RAB11A mutation during early embryonic development, we disrupted the homologous rab11a gene using CRISPR/Cas9 in zebrafish.ResultsThe affected boy who exhibited intellectual disability showed phenotypic features including cerebral atrophy, obesity, motor disability and abnormal muscle tone. Protein structure predictions indicated that RAB11A mutation affected protein stability and enzymatic activity. CRISPR/Cas9-mediated rab11a deficiency in zebrafish larvae significantly reduced brain, forebrain, and midbrain size.ConclusionOur study collectively demonstrated that the RAB11A mutation c.370A&gt;G is associated with neurodevelopmental disorders, characterized by motor deficits and brain anomalies. Additionally, we have successfully developed a zebrafish model to recapitulate these neurodevelopmental disorders associated with RAB11A deficiency, offering a valuable genetic resource for further investigation into this disease

Pattern recognition receptors in the development of nonalcoholic fatty liver disease and progression to hepatocellular carcinoma: An emerging therapeutic strategy

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and has become the leading chronic liver disease worldwide. NAFLD is viewed as the hepatic manifestation of metabolic syndrome, ranging from simple steatosis and nonalcoholic steatohepatitis (NASH) to advanced fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD progression is still not clear. Pattern recognition receptor (PRR)-mediated innate immune responses play a critical role in the initiation of NAFLD and the progression of NAFLD-related HCC. Toll-like receptors (TLRs) and the cyclic GMP-AMP (cGAMP) synthase (cGAS) are the two major PRRs in hepatocytes and resident innate immune cells in the liver. Increasing evidence indicates that the overactivation of TLRs and the cGAS signaling pathways may contribute to the development of liver disorders, including NAFLD progression. However, induction of PRRs is critical for the release of type I interferons (IFN-I) and the maturation of dendritic cells (DCs), which prime systemic antitumor immunity in HCC therapy. In this review, we will summarize the emerging evidence regarding the molecular mechanisms of TLRs and cGAS in the development of NAFLD and HCC. The dysfunction of PRR-mediated innate immune response is a critical determinant of NAFLD pathology; targeting and selectively inhibiting TLRs and cGAS signaling provides therapeutic potential for treating NALF-associated diseases in humans

Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic lesions in abdominal and pelvic malignancies: A systematic review and meta-analysis

PurposeThe purpose of this study is to compare the application value of 68Ga-FAPI and 18F-FDG PET/CT in primary and metastatic lesions of abdominal and pelvic malignancies (APMs).MaterialsThe search, limited to the earliest available date of indexing through 31 July 2022, was performed on PubMed, Embase, and Cochrane Library databases using a data-specific Boolean logic search strategy. We calculated the detection rate (DR) of 68Ga-FAPI and 18F-FDG PET/CT in the primary staging and recurrence of APMs, and pooled sensitivities/specificities based on lymph nodes or distant metastases.ResultsWe analyzed 473 patients and 2775 lesions in the 13 studies. The DRs of 68Ga-FAPI and 18F-FDG PET/CT in evaluating the primary staging and recurrence of APMs were 0.98 (95% CI: 0.95-1.00), 0.76 (95% CI: 0.63-0.87), and 0.91(95% CI: 0.61-1.00), 0.56 (95% CI: 0.44-0.68), respectively. The DRs of 68Ga-FAPI and 18F-FDG PET/CT in primary gastric cancer and liver cancer were 0.99 (95% CI: 0.96-1.00), 0.97 (95% CI: 0.89-1.00) and 0.82 (95% CI: 0.59-0.97), 0.80 (95% CI: 0.52-0.98), respectively. The pooled sensitivities of 68Ga-FAPI and 18F-FDG PET/CT in lymph nodes or distant metastases were 0.717(95% CI: 0.698-0.735) and 0.525(95% CI: 0.505-0.546), and the pooled specificities were 0.891 (95% CI: 0.858-0.918) and 0.821(95% CI: 0.786-0.853), respectively.ConclusionsThis meta-analysis concluded that 68Ga-FAPI and 18F-FDG PET/CT had a high overall diagnostic performance in detecting the primary staging and lymph nodes or distant metastases of APMs, but the detection ability of 68Ga-FAPI was significantly higher than that of 18F-FDG. However, the ability of 68Ga-FAPI to diagnose lymph node metastasis is not very satisfactory, and is significantly lower than that of distant metastasis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022332700.</jats:sec

Treatment of Non-small Cell Lung Cancer with AiDi Injection Based on Network Pharmacology

Abstract Background: This study aimed to determine the bioactive compounds, core genes, and pharmacological mechanisms underlying the effects of Aidi injection (ADI) in non‐small cell lung cancer (NSCLC), and to provide a further research directions. Material and Methods: The bioactive compounds of ADI were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and the Traditional Chinese Medicines Integrated Database, while targets related to these bioactive compounds and NSCLC were obtained from the GEO database. Cytoscape software was used to construct ingredients–protein-targets–pathway networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses and network analysis were performed to investigate potential mechanisms underlying the effects of ADI on NSCLC.Results: This study screened 45 bioactive compounds and 38 major proteins of ADI as potential agents that can act against NSCLC. The results revealed the following potential therapeutic targets of ADI in the treatment of NSCLC: FOS, VEGFA, EGFR, JUN, MMP9, IL2, STAT1, CASP1, NFKBA, and CDK2. The potential mechanisms via which ADI acts against NSCLC are closely related to the inhibition of apoptosis and the activation of signaling pathways. Conclusion: This study has revealed the multicompound, multitarget, and multichannel characteristics of ADI. This provides novel insight into further research investigations of the mechanism of ADI in NSCLC treatment.</jats:p