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

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

The Metabolomic Rationale for Treating Perimenopausal Syndrome as Kidney Deficiency

Background. Traditional Chinese medicine (TCM) typically attributes the etiopathogenesis of perimenopausal syndrome (PMS) to kidney deficiency in the TCM stratification system for diagnosis. However, the molecular basis of this classical attribution remains to be investigated. Aim of the Study. By unraveling the responses to TCM treatment for kidney deficiency, the metabolomic link between PMS and kidney deficiency can be evaluated for in-depth understanding of the mechanism of TCM treatment and development of better treatment protocols. Materials and Methods. With naturally aged rats as a model for PMS, the metabolomic response to TCM treatment for kidney deficiency was investigated by 1H NMR. Results. 1H NMR metabolomic evidence of plasma samples demonstrates that treatments with two classical TCM prescriptions for kidney deficiency, decoctions of Yougui and Zuogui, result in modulating the metabolic state of the disease model towards that of rats of younger age. Conclusion. The data support the notion that kidney deficiency is responsible, in part at least, for PMS, and the relevant prescriptions are helpful in dampening the changes in the body’s metabolic states to alleviate symptoms of the disorder

Additional file 1 of Risks of digestive diseases in long COVID: evidence from a population-based cohort study

Additional file 1: Figure S1. Directed Acyclic Graphs (DAG) for covariate selection. Figure S2. Flow chart of eligible participants’ selection. Figure S3. Distribution of follow-up time in the contemporary cohort (A) and the historical cohort (B). Figure S4. Hazard ratio of digestive outcomes in COVID-19 group and the contemporary comparison by severity of COVID-19. Table S1. Respiratory support treatments definition. Table S2. Outcome ascertainment. Table S3. The numbers (percentages) of participants with missing covariates. Table S4. Baseline characteristics of COVID-19 group and contemporary comparisons before weighting. Table S5. Hazard ratio of digestive outcomes in COVID-19 group and the contemporary comparison at different follow-up times. Table S6. Baseline characteristics of COVID-19, contemporary comparisons by severity of COVID-19 before weighting. Table S7. Baseline characteristics of COVID-19, contemporary comparisons by severity of COVID-19 after weighting. Table S8. Baseline characteristics of COVID-19 group and contemporary comparisons by status of SARS-CoV reinfection before weighting. Table S9. Baseline characteristics of COVID-19 group and contemporary comparisons by severity of SARS-CoV reinfection after weighting. Table S10. Hazard ratio of digestive outcomes in the reinfected group, single SARS-CoV-2 infection group, and non-infected comparisons. Table S11. Hazard ratio of digestive outcomes in reinfected group and single SARS-CoV-2 infection group in head-to-head comparison. Table S12. Baseline characteristics of COVID-19 group and contemporary comparisons in the sensitive analysis restricting to the period before vaccination was available before weighting. Table S13. Baseline characteristics of COVID-19 group and contemporary comparisons in the sensitive analysis restricting to the period before vaccination was available after weighting. Table S14. Hazard ratio of digestive outcomes in COVID-19 group and contemporary and historical comparisons in subgroups in the sensitive analysis restricting to the period before vaccination was available. Table S15. Hazard ratio of digestive outcomes in COVID-19 group compared to the contemporary and historical comparisons by pooling estimates across all five imputed datasets. Table S16. Hazard ratio of digestive outcomes compared with contemporary and historical comparisons in subgroups. Table S17. Hazard ratio of digestive outcomes in COVID-19 group, the contemporary and historical comparison by sex. Table S18. Baseline characteristics of COVID-19 group and historical comparisons before weighting. Table S19. Baseline characteristics of COVID-19 group and historical comparisons after weighting. Table S20. Baseline characteristics of COVID-19 group and historical comparisons by severity of COVID-19 before weighting. Table S21. Baseline characteristics of COVID-19 group and historical comparisons by severity of COVID-19 after weighting. Table S22. Baseline characteristics of COVID-19 group and historical comparisons in the sensitive analysis restricting to the period before vaccination was available before weighting. Table S23. Baseline characteristics of COVID-19 group and historical comparisons in the sensitive analysis restricting to the period before vaccination was available after weighting. Table S24. Hazard ratio of digestive outcomes in COVID-19 group and the historical comparison by severity of COVID-19

Spin transport in the Néel and collinear antiferromagnetic phase of the two dimensional spatial and spin anisotropic Heisenberg model on a square lattice

We analyze and compare the effect of spatial and spin anisotropy on spin conductivity in a two dimensional S=1/2 Heisenberg quantum magnet on a square lattice. We explore the model in both the Neel antiferromagnetic (AF) phase and the collinear antiferromagnetic (CAF) phase. We find that in contrast to the effects of spin anisotropy in the Heisenberg model, spatial anisotropy in the AF phase does not suppress the zero temperature regular part of the spin conductivity in the zero frequency limit - rather it enhances it. We also explore the finite temperature effects on the Drude weight in the AF phase for various spatial and spin anisotropy parameters. We find that the Drude weight goes to zero as the temperature approaches zero. At finite temperatures (within the collision less approximation) enhancing spatial anisotropy increases the Drude weight value and increasing spin anisotropy decreases the Drude weight value. In the CAF phase (within the non-interacting approximation) the zero frequency spin conductivity has a finite value for non-zero values of the spatial anisotropy parameter. In the CAF phase increasing the spatial anisotropy parameter suppresses the regular part of the spin conductivity response at zero frequency. Furthermore, we find that the CAF phase displays a spike in the spin conductivity not seen in the AF phase. Inclusion of the smallest amount of spin anisotropy causes a gap to develop in the spin conductivity response of both the AF and CAF phase. Based on these studies we conclude that materials with spatial anisotropy are better spin conductors than those with spin anisotropy both at zero and finite temperatures. We utilize exchange parameter ratios for real material systems as inputs to the computation of spin conductivity.Comment: 10 pages, 8 figure