Visnagin treatment attenuates DSS-induced colitis by regulating inflammation, oxidative, stress, and mucosal damage

Ulcerative colitis (UC), is a chronic inflammatory bowel disease characterized by recurrent episodes of inflammation and ulceration of the colonic mucosa. This study aimed to explore the therapeutic potential effects of visnagin (VIS), a natural furanochromone using a murine model, focusing on tight junction protein expression, oxidative stress, apoptosis and associated inflammation in a dextran sodium sulfate (DSS) induced UC model. A total of 36 male C57BL/6 mice were divided randomly into six groups (n = 6): Group 1 served as the control, group 2, treated with DSS (2% with three 5-day cycles diluted in distilled water administered orally). Group 3 (VIS) perse alone (60 mg/kg b. wt), orally for 31 days, Group 4-low dose of VIS (30 mg/kg b. wt for 31 days with DSS, group 5-high dose VIS (60 mg/kg b. wt) for 31 days with DSS and Group 6 Dexamethasone sodium @ 1 mg/kg b. wt-IP with DSS for 31 days. Disease progression and therapeutic outcomes were assessed by monitoring clinical symptoms, body weight changes, colon length, Disease activity index (DAI), oxidative stress indices, gross and histopathological analysis, inflammatory cytokine levels and immunohistochemical expression. Results demonstrated that VIS co-administration, particularly at high doses, significantly mitigated DSS-induced weight loss, colon shortening. This protective effect was further supported by a significant reduction in oxidative and nitrosative stress which was evident from decreased levels of nitrite and Malondialdehyde (MDA) in VIS treated groups 4 and 5. Further, VIS suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ, NF-κB, IL-17, MPO and TGF-β) while increasing anti-inflammatory IL-10 levels in colon tissues. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed significantly reduced mRNA expression of TNF-α and IL-17 along with increased occludin expression in groups 4, 5 and 6. VIS also improves intestinal barrier by increasing the expression of tight junction occludin, as confirmed through RT-PCR. Immunohistochemical analysis showed strong positive immunoreactivity for NF-κB, COX-2, NLRP3 and TNF-α in DSS group, which wa notably reduced in VIS-treated groups. Additionally, VIS improved intestinalbarrier integrity by upregulating occluding expression. Histopathological analysis further confirmed that VIS attenuated DSS-induecdcolonic lesions. In conclusion, VIS exhibits potent anti-inflammatory and mucosal-protective properties, making it a promising therapeutic candidate for managing UC. Its ability to modulate inflammatory pathways and enhance intestinal barrier function suggests its potential as an alternative treatment for UC

Phenotypic characterisation and prevalence of carbapenem-resistant Enterobacterales in a tertiary care centre in Bihar India

Abstract Carbapenem-resistant Enterobacterales (CRE) infections pose a global health threat due to limited treatment options. This study aimed to determine the prevalence, phenotypic characteristics, and distribution of CRE classes in Bihar, India. A cross-sectional study was conducted from July 2021 to July 2023. CRE detection involved modified carbapenem inactivation and EDTA-modified carbapenem inactivation methods, coupled with carbapenemase inhibition tests (Combined disc tests) to classify them into various phenotypes. Antibiotic susceptibility patterns and phenotypic class distribution were determined. Statistical analysis was performed using SPSS v.23. Among 3421 Enterobacterales isolates, 32.97% exhibited carbapenem resistance. Inpatients showed higher resistance (47.74%) compared to outpatients (14.48%). Resistance was prominent in respiratory (68.09%) and pus samples (56.99%). Most CRE were Escherichia coli (31.3% in pus, 22.4% in urine). Resistance to third-generation cephalosporins, BL-BLI combinations, and Aztreonam was high. Colistin resistance was observed in one isolate. Class B carbapenemases were predominant (70% in E. coli, 55% in Klebsiella pneumoniae). Co-expression of Class A and Class B carbapenemases was observed in 23% of E. coli and 36.2% of K. pneumoniae isolates. This study reveals a high prevalence of CRE in Bihar, India, with concerning antimicrobial resistance patterns. Class B carbapenemases predominate, warranting the development of effective interventions, including screening, isolation, hand hygiene, and antibiotic stewardship, to combat CRE’s spread. Standardized phenotypic tests can guide therapy and infection control, especially in resource-limited settings. Research and development of new antibiotics are urgently needed to address this growing public health concern

Rupture model of Mw 7.8 2015 Gorkha, Nepal earthquake: constraints from GPS measurements of coseismic offsets

We estimate coseismic offsets at 20 sites in India due to the 25 April 2015 Gorkha, Nepal (Mw 7.8) earthquake. Only four sites in the Indian region, immediately to the south of the rupture, showed discernible coseismic horizontal offsets ranging between 3 and 7 mm toward north. We invert these offsets along with 13 other offsets at GPS sites in Nepal and 33 offsets at sites in China, for the estimation of slip distribution on the causative rupture. We assume that rupture occurred on the Main Himalayan Thrust (MHT). In our estimated slip model, high slip reaching ∼5 m occurred east of the mainshock epicenter, and the slip on rupture terminated close to the Main Boundary Thrust (MBT). Thus the rupture for this earthquake remained blind, increasing the potential for future earthquake in the shallow, updip unruptured part of the MHT