Current therapy option for necrotizing enterocolitis: Practicalities and challenge

Necrotizing enterocolitis (NEC) is one of the most prevalent neonatal gastrointestinal disorders. Despite ongoing breakthroughs in its treatment and prevention, the incidence and mortality associated with NEC remain high. New therapeutic approaches, such as breast milk composition administration, stem cell therapy, immunotherapy, and fecal microbiota transplantation (FMT) have recently evolved the prevention and the treatment of NEC. This study investigated the most recent advances in NEC therapeutic approaches and discussed their applicability to bring new insight to NEC treatment

Investigating the Mechanisms of Bisdemethoxycurcumin in Ulcerative Colitis: Network Pharmacology and Experimental Verification

Ulcerative colitis is a chronic inflammatory bowel disorder that is hard to cure once diagnosed. Bisdemethoxycurcumin has shown positive effects on inflammatory diseases. However, the underlying bioactive interaction between bisdemethoxycurcumin and ulcerative colitis is unclear. The objective of this study was to determine the core target and potential mechanism of action of bisdemethoxycurcumin as a therapy for ulcerative colitis. The public databases were used to identify potential targets for bisdemethoxycurcumin and ulcerative colitis. To investigate the potential mechanisms, the protein-protein interaction network, gene ontology analysis, and Kyoto encyclopedia of genes and genomes analysis have been carried out. Subsequently, experimental verification was conducted to confirm the findings. A total of 132 intersecting genes of bisdemethoxycurcumin, as well as ulcerative coli-tis-related targets, were obtained. SRC, EGFR, AKT1, and PIK3R1 were the targets of highest potential, and the PI3K/Akt and MAPK pathways may be essential for the treatment of ulcerative colitis by bisdemethoxycurcumin. Molecular docking demonstrated that bisdemethoxycurcumin combined well with SRC, EGFR, PIK3R1, and AKT1. Moreover, the in vitro experiments suggested that bisdemethoxycurcumin might reduce LPS-induced pro-inflammatory cytokines levels in RAW264.7 cells by suppressing PI3K/Akt and MAPK pathways. Our study provided a comprehensive overview of the potential targets and molecular mechanism of bisdemethoxycurcumin against ulcerative colitis. Furthermore, it also provided a theoretical basis for the clinical treatment of ulcerative colitis, as well as compelling evidence for further study on the mechanism of bisdemethoxycurcumin in the treatment of ulcerative colitis

Protective Effects of Crocetin against Radiation-Induced Injury in Intestinal Epithelial Cells

Background and Aims. Treatment options for radiation-induced intestinal injury (RIII) are limited. Crocetin has been demonstrated to exert antioxidant, antiapoptotic, and anti-inflammatory effects on various diseases. Here, we investigate the effects of crocetin on RIII in vitro. Materials and Method. IEC-6 cells exposed to 10 Gy of radiation were treated with different doses of crocetin (0, 0.1, 1, 10, and 100 μM), and cell viability was assessed by CCK-8. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ) in culture supernatants were measured using colorimetric and ELISA kits, respectively. Cellular apoptosis was evaluated by Annexin V/PI double staining. Results. Crocetin dose-dependently improved the survival of irradiated IEC-6 cells with the optimal dose of 10 μM, as indicated by the reduction of cellular apoptosis, decreased levels of MDA, MPO, and proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ), and increased activities of antioxidative enzymes (SOD, CAT, and GPx). Conclusion. Our findings demonstrated that crocetin alleviated radiation-induced injury in intestinal epithelial cells, offering a promising agent for radioprotection

Coupling Molecularly Ultrathin Sheets of NiFe-Layered Double Hydroxide on NiCo₂O₄ Nanowire Arrays for Highly Efficient Overall Water-Splitting Activity

Developing efficient but nonprecious bifunctional electrocatalysts for overall water splitting in basic media has been the subject of intensive research focus with the increasing demand for clean and regenerated energy. Herein, we report on the synthesis of a novel hierarchical hybrid electrode, NiFe-layered double hydroxide molecularly ultrathin sheets grown on NiCo₂O₄ nanowire arrays assembled from thin platelets with nickel foam as the scaffold support, in which the catalytic metal sites are more accessible and active and most importantly strong chemical coupling exists at the interface, enabling superior catalytic power toward both oxygen evolution reaction (OER) and additionally hydrogen evolution reaction (HER) in the same alkaline KOH electrolyte. The behavior ranks top-class compared with documented non-noble HER and OER electrocatalysts and even comparable to state-of-the-art noble-metal electrocatalysts, Pt and RuO₂. When fabricated as an integrated alkaline water electrolyzer, the designed electrode can deliver a current density of 10 mA cm^–2 at a fairly low cell voltage of 1.60 V, promising the material as efficient bifunctional catalysts toward whole cell water splitting

Adverse clinical outcomes and immunosuppressive microenvironment of RHO-GTPase activation pattern in hepatocellular carcinoma

Abstract Background Emerging evidence suggests that Rho GTPases play a crucial role in tumorigenesis and metastasis, but their involvement in the tumor microenvironment (TME) and prognosis of hepatocellular carcinoma (HCC) is not well understood. Methods We aim to develop a tumor prognosis prediction system called the Rho GTPases-related gene score (RGPRG score) using Rho GTPase signaling genes and further bioinformatic analyses. Results Our work found that HCC patients with a high RGPRG score had significantly worse survival and increased immunosuppressive cell fractions compared to those with a low RGPRG score. Single-cell cohort analysis revealed an immune-active TME in patients with a low RGPRG score, with strengthened communication from T/NK cells to other cells through MIF signaling networks. Targeting these alterations in TME, the patients with high RGPRG score have worse immunotherapeutic outcomes and decreased survival time in the immunotherapy cohort. Moreover, the RGPRG score was found to be correlated with survival in 27 other cancers. In vitro experiments confirmed that knockdown of the key Rho GTPase-signaling biomarker SFN significantly inhibited HCC cell proliferation, invasion, and migration. Conclusions This study provides new insight into the TME features and clinical use of Rho GTPase gene pattern at the bulk-seq and single-cell level, which may contribute to guiding personalized treatment and improving clinical outcome in HCC

Long-term risks of respiratory diseases in patients infected with SARS-CoV-2: a longitudinal, population-based cohort studyResearch in context

Summary: Background: In the post-pandemic era, growing apprehension exists regarding the potential sequelae of COVID-19. However, the risks of respiratory diseases following SARS-CoV-2 infection have not been comprehensively understood. This study aimed to investigate whether COVID-19 increases the long-term risk of respiratory illness in patients with COVID-19. Methods: In this longitudinal, population-based cohort study, we built three distinct cohorts age 37–73 years using the UK Biobank database; a COVID-19 group diagnosed in medical records between January 30th, 2020 and October 30th, 2022, and two control groups, a contemporary control group and a historical control group, with cutoff dates of October 30th, 2022 and October 30th, 2019, respectively. The follow-up period of all three groups was 2.7 years (the median (IQR) follow-up time was 0.8 years). Respiratory outcomes diagnosed in medical records included common chronic pulmonary diseases (asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), pulmonary vascular disease (PVD), and lung cancer. For the data analysis, we calculated hazard ratios (HRs) along with their 95% CIs using Cox regression models, following the application of inverse probability weights (IPTW). Findings: A total of 3 cohorts were included in this study; 112,311 individuals in the COVID-19 group with a mean age (±SDs) of 56.2 (8.1) years, 359,671 in the contemporary control group, and 370,979 in the historical control group. Compared with the contemporary control group, those infected with SARS-CoV-2 exhibited elevated risks for developing respiratory diseases. This includes asthma, with a HR of 1.49 and a 95% CI 1.28–1.74; bronchiectasis (1.30; 1.06–1.61); COPD (1.59; 1.41–1.81); ILD (1.81; 1.38–2.21); PVD (1.59; 1.39–1.82); and lung cancer (1.39; 1.13–1.71). With the severity of the acute phase of COVID-19, the risk of pre-described respiratory outcomes increases progressively. Besides, during the 24-months follow-up, we observed an increasing trend in the risks of asthma and bronchiectasis over time. Additionally, the HR of lung cancer for 0–6 month follow-up was 3.07 (CI 1.73–5.44), and the association of lung cancer with COVID-19 disease disappeared at 6–12 month follow-up (1.06; 0.43–2.64) and at 12–24 months (1.02; 0.45–2.34). Compared to those with one SARS-CoV-2 infection, reinfected patients were at a higher risk of asthma (3.0; 1.32–6.84), COPD (3.07; 1.42–6.65), ILD (3.61; 1.11–11.8), and lung cancer (3.20; 1.59–6.45). Similar findings were noted when comparing with a historical cohort serving as a control group, including asthma (1.31; 1.13–1.52); bronchiectasis (1.53; 1.23–1.89); COPD (1.41; 1.24–1.59); ILD (2.53; 2.05–3.13); PVD (2.30; 1.98–2.66); and lung cancer (2.23; 1.78–2.79). Interpretation: Our research suggests that patients with COVID-19 may have an increased risk of developing respiratory diseases, and the risk increases with the severity of infection and reinfection. Even during the 24-month follow-up, the risk of asthma and bronchiectasis continued to increase. Hence, implementing appropriate follow-up strategies for these individuals is crucial to monitor and manage potential long-term respiratory health issues. Additionally, the increased risk in lung cancer in the COVID-19 individuals was probably due to the diagnostic tests conducted and incidental diagnoses. Funding: The National Natural Science Foundation of China of China Regional Innovation and Development Joint Foundation; National Natural Science Foundation of China; Program for High-level Foreign Expert Introduction of China; Natural Science Foundation for Distinguished Young Scholars of Guangdong Province; Guangdong Basic and Applied Basic Research Foundation; Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People’s Hospital; VA Clinical Merit and ASGE clinical research funds

Metabonomics Reveals Plasma Metabolic Changes and Inflammatory Marker in Polycystic Ovary Syndrome Patients

Polycystic ovary syndrome (PCOS) is a common, clinically heterogeneous endocrine disorder affecting women of reproductive age, associated with endocrinopathy and metabolic abnormalities. Although some metabolic parameters have been investigated, very little information has been reported on the changes of small metabolites in biofluids. The aim of this study was to establish the metabolic profile of PCOS and compare it with that of controls. In this cross-sectional study of 34 women with PCOS and 36 controls, contents of small metabolites and lipids in plasma samples were measured using nuclear magnetic resonance (NMR)-based techniques and analyzed using multivariate statistical methods. Significant decrease (<i>P</i> < 0.05) in the levels of amino acids (leucine, isoleucine, methionine, glutamine, and arginine), citrate, choline, and glycerophosphocholine/phosphocholine (GPC/PC), and increase (<i>P</i> < 0.05) in the levels of lactate, dimethylamine (DMA), creatine, and N-acetyl glycoproteins were observed in PCOS patients compared with the controls. Subgroups of patients with obesity, metabolic syndrome, or hyperandrogenism exhibited greater metabolic deviations than their corresponding subgroups without these factors. PCOS patients have perturbations in amino acid metabolism, the tricarboxylic acid (TCA) cycle, and gut microflora, as well as mild disturbances in glucose and lipid metabolism. The elevated level of <i>N</i>-acetyl glycoproteins demonstrates the existence of low-grade chronic inflammation in PCOS patients