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Introduction: Epidemiological studies have implicated ovulation as a risk factor for ovarian high-grade serous carcinoma (HGSC) at the initiation stage. Precancerous lesions of HGSC commonly exhibit TP53 mutations attributed to DNA deamination and are frequently localized in the fallopian tube epithelium (FTE), a site regularly exposed to ovulatory follicular fluid (FF). This study aimed to assess the mutagenic potential of FF and investigate the expression levels and functional role of activation-induced cytidine deaminase (AID) following ovulation, along with the resulting TP53 DNA deamination., Methods: The mutagenic activity of FF toward premalignant and malignant FTE cells was determined using the hypoxanthine phosphoribosyl transferase (HPRT) mutation assay with or without AID knockdown. The sequential activation of AID, including expressional induction, nuclear localization, DNA binding, and deamination, was determined. AID inducers in FF were identified, and the times of action and signaling pathways were determined., Results: FF induced AID activation and de novo FTE cell mutagenesis in two waves of activity in accordance with post-ovulation FF exposure. The ERK-mediated early activity started at 2 min and peaked at 45 min, and the NF-κB-mediated late activity started at 6 h and peaked at 8.5 h after exposure. ROS, TNF-α, and estradiol, which are abundant in FF, all induced the two activities, while all activities were abolished by antioxidant cotreatment. AID physically bound to and biochemically deaminated the TP53 gene, regardless of known mutational hotspots. It did not act on other prevalent tumor-suppressor genes of HGSC., Conclusion: This study revealed the ROS-dependent AID-mediated mutagenic activity of the ovulatory FF. The results filled up the missing link between ovulation and the initial TP53 mutation and invited a strategy of antioxidation in prevention of HGSC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Effective drug delivery for is the foremost requirement for the complete recovery of the disease. Nanomedicine and nanoengineering has provided so many spaces and ideas for the drug delivery design, whether controlled, targeted, or sustained. Different types of nanocarriers or nanoparticles are aggressively designed for the drug delivery applications. Clay minerals are identified as a one of the potential nanocarrier for the drug delivery. Owing to their biocompatibility and very low cytotoxicity, clay minerals showing effective therapeutic applications. In the present investigation, clay mineral, i.e., Halloysite nano tubes are utilized as a nanocarrier for the delivery of antibiotic cefixime (CFX), a third-generation cephalosporin. The HNT was first functionalized with the sulfuric acid and then further treated with the 3-(aminopropyl)triethoxysilane (APTES). The drug is loaded on three different classifications of HNTs, i.e., Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT and their comparative analysis is established. Different characterization techniques such as X-ray diffractometry (XRD), Fourier transform infra-red (FT-IR), Transmission electron microscopy TEM), Brunauer-Emmett-Teller (BET), adsorption studies, and Thermogravimetric analysis (TGA) were performed to evaluate their chemical, structural, morphological, and thermal properties. TGA confirmed the encapsulation efficiency of Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT as 42.65, 52.19, and 53.43%, respectively. Disk diffusion and MTT assay confirmed that the drug loaded HNTs have potential antibacterial activities and less cytotoxicity. The adsorption capacity of CFX with different HNTs are evaluated and Different adsorption and kinetic models have been discussed. Drug release studies shows that APTES-CFX-HNT showing sustained release of cefixime as compared to Bare-CFX-HNT and Acid-CFX-HNT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The textiles for medical use and the purification of textile factory effluents have become the most crucial part of the human healthcare sector. In this study bioactive compounds produced by four distinct plant extracts were used for the synthesis of zinc oxide nanoparticles. The four different ZnO nanoparticles were comprehensively characterized by different analytical techniques. XRD analysis revealed the crystalline nature and phase purity of the ZnO nanoparticles. FTIR spectra provided information on the function of plant extracts in the stabilization or capping process. The size distribution and morphological diversity of the nanoparticles were further clarified by SEM and TEM images. The photocatalytic degradation activity of the four ZnO nanoparticles on two different dyes showed that ZnO nanoparticles prepared from A. indica were most effective for the degradation of 98 % and 91 % of Rhodamine B and Alizarin red dye respectively. The selected ZnO nanoparticles from A. indica were used to prepare ZnO-chitosan nanocomposites before coating on cotton fabrics. The hydrophobicity, UV protection factor, and antibacterial activity of ZnO-chitosan nanocomposites, when coated on cotton fabrics, were also examined. The overall results demonstrated the ZnO and ZnO-chitosan nanocomposite prepared in the present study as a promising material for environmental remediation application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Idiosyncratic drug-induced liver injury (iDILI) causing acute liver failure (ALF) carries high short-term mortality and patients who meet King's College criteria for liver transplantation have 1-month survival of 34% without liver transplantation (PMID: 20949552). We present our experience with low-volume plasma exchange (PLEX-LV, 50% of estimated plasma volume exchanged per session) and low-dose steroid to treat iDILI ALF., Methods: We retrospectively analysed data of patients with iDILI (diagnosed as per RUCAM score), treated with PLEX-LV and low-dose steroid (prednisolone: 10 mg OD, with rapid taper) in our department from 2016 to 2022. Baseline and dynamic parameters (post-PLEX) were assessed as predictors of 1-month liver transplantation-free survival., Results: Twenty-two iDILI patients [probable: possible iDILI: 20:2, males: 9, age: 30 (14-84) years, median (range); MELD score: 30.5 (19-43)] underwent PLEX-LV for ALF during the study period. Causative agents were complementary and alternative medications (36%), antiepileptics (18%) antimicrobials (14%), antitubercular drugs (14%), antifungal drugs (9%) and others (9%). All patients had jaundice and encephalopathy; 9 patients also had ascites. None of the patients underwent liver transplantation. Study patients underwent 3 (1-7) PLEX sessions and 1.4 (0.6-1.6) litres of plasma was exchanged per session. One-month transplant-free survival was 59% (13/22) in the study population and 63% (12/19) among patients who fulfilled Kings College criteria for liver transplantation. Reduction of ≥25% in plasma von Willebrand factor (VWF) levels after PLEX-LV predicted improved survival (HR: 0.09, 95% CI: 0.01-0.65; AUROC: 0.81; 95% CI: 0.6-1.0)., Conclusion: Low-volume PLEX and low-dose steroid appears a promising treatment option in patients with iDILI-induced ALF not opting for liver transplantation. Dynamic changes in VWF level after PLEX predict 1-month survival in these patients., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Clay minerals such as Halloysite nanotubes (HNTs), abundantly available green nanomaterial, exhibit a significant advantage in biomedical applications such as drug delivery, antibacterial and antimicrobials, tissue engineering or regeneration, etc. Because of the mesoporous structure and high absorbability, HNTs exhibit great potential as a nanocarrier in drug delivery applications. The sulfuric acid treatment enhances the surface area of the HNTs and thereby improves their drug-loading capacity by enlarging their lumen space/inner diameter. In the present investigation, based on the literature that supports the efficacy of drug loading after acid treatment, a dual treatment was performed to functionalize the HNTs surface. First, the HNTs were etched and functionalized using sulfuric acid. The acid-functionalized HNTs underwent another treatment using (3-aminopropyl) triethoxysilane (APTES) to better interact the drug molecules with the HNTs surfaces for efficient drug loading. Augmentin, a potential drug molecule of the penicillin group, was used for HNTs loading, and their antibacterial properties, cytotoxicity, and cumulative drug release (%) were evaluated. Different characterization techniques, such as X-ray diffractometer (XRD) and Fourier Transform Infra-Red (FT-IR), confirm the loading of Augmentin to the APTES@Acid HNTs. TEM images confirm the effective loading of the drug molecule with the HNTs. The drug encapsulation efficiency shows 40.89%, as confirmed by the Thermogravimetric Analysis (TGA). Also, the Augmentin-loaded APTES@Acid HNTs exhibited good antibacterial properties against E. coli and S. aureus and low cytotoxicity, as confirmed by the MTT assay. The drug release studies confirmed the sustainable release of Augmentin from the APTES@Acid HNTs. Hence, the treated HNTs can be considered as a potential nanocarrier for effectively delivering Augmentin and promoting enhanced therapeutic benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Wastewater treatment remains the most significant delinquent issue world-wide. Generally, wastewater treatment involves filtration followed by acidified de-emulsification through photocatalytic reduction. The aim of the present study is to reduce the use of nanoparticles in wastewater treatment and also to find an appropriate alternative to replace cotton fiber filters used in water treatment plant. The cotton fiber filters are highly prone to bacterial film development leading to bactericidal degradation of the fibers. We developed a ZnO-chitosan nanocomposite coated fiber for wastewater treatment to enhance its photocatalytic activity under acidic condition. The fiber showed high degree of photocatalytic degradation activity, reducing rhodamine B dye, chemical oxygen demand and chromium levels in the synthetic wastewater to 37, 79 and 51% respectively under highly acidic condition. Additionally, ZnO-chitosan nanocomposite did not cause mortality on Danio rerio embryo after 72 h incubation. The ZnO-chitosan nanocomposite coated fiber showed strong antibacterial activity against Escherichia coli and Staphylococcus aureus with a reduction of 96% and 99% respectively. This study demonstrated the potential of a novel smart fiber in wastewater treatment and biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In a prior report, no patient with rodenticidal hepatotoxicity who met Kochi criteria (MELD score ≥36 or baseline INR ≥6 with hepatic encephalopathy) (PMID: 26310868) for urgent liver transplantation survived with medical management alone. Plasma exchange (PLEX) may improve survival in these patients., Objectives: We describe our experience with low-volume PLEX (PLEX-LV) in treating rodenticide ingestion induced hepatotoxicity in children., Methods: From prospectively collected database of rodenticidal hepatotoxicity patients managed as in-patient with department of Hepatology from December 2017 to August 2021, we retrospectively studied outcomes in children (≤18 years). Hepatotoxicity was categorized as acute liver injury (ALI, coagulopathy alone) or acute liver failure (ALF, coagulopathy and encephalopathy). Kochi criteria was used to assess need for urgent liver transplantation. The primary study outcome was one-month survival., Results: Of the 110 rodenticidal hepatotoxicity patients, 32 children (females: 56%; age: 16 [4.7-18] years; median, range) constituted the study patients. The study patients presented 4 (1-8) days after poison consumption (impulsive suicidal intent:31, accidental:1). Twenty children (62%) had ALI [MELD: 18 (8-36)] and 12 (38%) had ALF [MELD: 37 (24-45)].All children received standard medical care, including N-acetyl cysteine; ALF patients also received anti-cerebral edema measures. None of the patient families opted for liver transplantation. Seventeen children (ALI: 6, ALF: 11) were treated with PLEX-LV (3 [1-5] sessions, volume of plasma exchanged per session: 26 [13-38] ml/kg body weight) and peri-procedure low dose prednisolone.At 1 month, 28 of the 32 children (87.5%) were alive (4 ALF patients died). Of 10 children who met Kochi listing criteria for urgent liver transplantation, two children were ineligible for PLEX-LV (due to hemodynamic instability) and of the remaining 8 children treated by PLEX-LV, 6 (75%) survived., Conclusions: PLEX-LV shows promise as an effective non-liver transplant treatment in children with rodenticidal hepatotoxicity., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

An interaction of homophthalonitrile with salicylaldehydes proceeds as a novel domino reaction and results in the formation of nineteen 12H-chromeno[2,3-c]isoquinoline-5-amine derivatives. Four new bonds and two cycles are forged in a single synthetic operation, employing cheap and eco-friendly ammonium formate, acting both as a catalyst and a reducing agent. The in vitro cytotoxicity tests revealed antiproliferative activities against five human tumor cell lines, including the cisplatin-resistant ovarian carcinoma one (A2780cp8), with inhibitory potency data (IC 50 ) in the low micromolar range in most cases. Molecular docking calculations and fluorescence quenching studies revealed possible binding properties with DNA of the active compounds., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The study is aimed to synthesize potent metal oxide based biomimetic nanocomposites to overcome the risk associated with artificial bone tissue engineering. High purity TiO 2 nanoparticles are synthesized via hydrothermal route. A biomimetic nanocomposite scaffolds containing chitosan-sodium alginate (4: 4) blended with three different (0.5, 1, and 1.5 wt%) concentrations of hydrothermally synthesized TiO 2 nanoparticles are obtained by solvent casting technique. The physico-chemical and thermal degradation properties of as-synthesized TiO 2 nanoparticles and their nanocomposite scaffolds are analyzed. In-vitro cytotoxicity and biocompatibility of the prepared TiO 2 nanoparticles and nanocomposites are tested against human bladder tumor (UC6) and osteosarcoma (MG-63) cell lines. Antibacterial property is tested against Escherichia coli and Staphylococcus aureus. These studies reveal that TiO 2 nanoparticles and polymeric nanocomposites contain good physico-chemical and mechanical properties for enhanced in-vitro biocompatibility suitable for biomedical applications. Biomimetically prepared chitosan-sodium alginate scaffold containing TiO 2 nanoparticles (1 wt%) is found to exhibit superior biocompatibility for bone tissue engineering applications., (Copyright © 2020. Published by Elsevier B.V.)

Inflammation and cellular energetics play critical roles in organ dysfunction following hemorrhagic shock. Recent studies suggest a putative role for sirtuin 1 (SIRT1) in potentiating mitochondrial function and improving organ function following hemorrhagic shock in animal models. SIRT1 is an NAD + dependent protein deacetylase and increased availability of NAD + has been shown to augment SIRT1 activity. As niacin is a precursor of NAD + , in this study, we tested whether niacin can improve survival following hemorrhagic shock. However niacin also mediates its biological action by binding to its receptor, hydroxyl-carboxylic acid receptor 2 (HCA2 or Gpr109a); so we examined whether the effect of niacin is mediated by binding to Gpr109a or by increasing NAD + availability. We found that niacin administered intravenously to rats subjected to hemorrhagic injury (HI) in the absence of fluid resuscitation resulted in a significantly prolonged duration of survival. However, treatment of rats with similar doses of nicotinamide mononucleotide (NMN), a precursor to NAD + that does not bind Gpr109a, did not extend survival following HI. The duration of survival due to niacin treatment was significantly reduced in Gpr109a -/- mice subjected to HI. These experiments demonstrated that the Gpr109a receptor-mediated pathway contributed significantly to niacin mediated salutary effect. Further studies showed improvement in markers of cellular energetics and attenuation of inflammatory response with niacin treatment. In conclusion, we report that Gpr109a-dependent signalling is important in restoring cellular energetics and immunometabolism following hemorrhagic shock., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Pseudomonas aeruginosa is one of the most common opportunistic pathogens that cause severe infections in humans. The burden of carbapenem resistance is particularly high and is on the rise. Very little information is available on the molecular mechanisms and its clonal types of carbapenem-resistant P. aeruginosa seen in Indian hospitals. This study was undertaken to monitor the β-lactamase profile and to investigate the genetic relatedness of the carbapenemase-producing (CP) P. aeruginosa collected across different hospitals from India., Materials and Methods: A total of 507 non-duplicate, carbapenem-resistant P. aeruginosa isolated from various clinical specimens collected during 2014-2017 across seven Indian hospitals were included. Conventional multiplex polymerase chain reaction for the genes encoding beta-lactamases such as extended-spectrum beta-lactamase (ESBL) and carbapenemase were screened. A subset of isolates (n = 133) of CP P. aeruginosa were genotyped by multilocus sequence typing (MLST) scheme., Results: Of the total 507 isolates, 15%, 40% and 20% were positive for genes encoding ESBLs, carbapenemases and ESBLs + carbapenemases, respectively, whilst 25% were negative for the β-lactamases screened. Amongst the ESBL genes, bla VEB is the most predominant, followed by bla PER and bla TEM , whilst bla VIM and bla NDM were the most predominant carbapenemases seen. However, regional differences were noted in the β-lactamases profile across the study sites. Genotyping by MLST revealed 54 different sequence types (STs). The most common are ST357, ST235, ST233 and ST244. Six clonal complexes were found (CC357, CC235, CC244, CC1047, CC664 and CC308). About 24% of total STs are of novel types and these were found to emerge from the high-risk clones., Conclusion: This is the first large study from India to report the baseline data on the molecular resistance mechanisms and its association with genetic relatedness of CP P. aeruginosa circulating in Indian hospitals. bla VIM - and bla NDM -producing P. aeruginosa is the most prevalent carbapenemase seen in India. Majority of the isolates belongs to the high-risk international clones ST235, ST357 and ST664 which is a concern., Competing Interests: There are no conflicts of interest

The regulation of mitochondrial function is critical in cellular homeostasis following hemorrhagic shock. Hemorrhagic shock results in fluid loss and reduced availability of oxygen and nutrients to tissues. The spleen is a secondary lymphoid organ playing a key role in 'filtering the blood' and in the innate and adaptive immune responses. To understand the molecular basis of hemorrhagic shock, we investigated the changes in splenocyte mitochondrial respiration, and concomitant immune and metabolic alterations. The hemorrhagic injury (HI) in our rat model was induced by bleeding 60% of the total blood volume followed by resuscitation with Ringers lactate. Another group of animals was subjected to hemorrhage, but did not receive fluid resuscitation. Oxygen consumption rate of splenocytes were determined using a Seahorse analyzer. We found a significantly reduced oxygen consumption rate in splenocytes following HI compared to sham operated rats. The mitochondrial stress test revealed a decreased basal oxygen consumption rate, ATP production, maximal respiration and spare respiratory capacity. The mitochondrial membrane potential, and citrate synthase activity, were also reduced in the splenocytes following HI. Hypoxic response in the splenocyte was confirmed by increased gene expression of Hif1α. Elevated level of mitochondrial stress protein, hsp60 and induction of high mobility group box1 protein (HMGB1) were observed in splenocytes following HI. An increased inflammatory response was demonstrated by significantly increased expression of IL-6, IFN-β, Mip-1α, IL-10 and NFκbp65. In summary, we conclude that splenocyte oxidative phosphorylation and metabolism were severely compromised following HI., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Present study was designed to survey the status of benzimidazole (BZ) resistance in goat flocks of different agro climatic regions of Uttar Pradesh (U.P.), India by faecal egg count reduction test (FECRT) and allele specific PCR (AS-PCR). Faecal egg counts and larval culture were made from representative samples of all regions. The results of the faecal culture and PCR-RFLP on beta tubulin isotype-1 gene showed Haemonchus contortus was predominant species. FECRT results showed BZ resistance prevalent in all regions. However, six farms of twenty screened, harboured susceptible populations of strongyles. Three hundred H. contortus infective larvae from all regions of the state were genotyped for BZ resistance. AS-PCR results revealed 55-85% of H. contortus homozygous resistant (rr), 10-21% homozygous susceptible (SS) and 5-24% heterozygous (rS) among different regions of U.P. The allele frequencies were 67-87.5% for resistant (TTC) and 12.5-33% for susceptible (TAC). The survey indicated that the status of BZ resistance is in alarming conditions in all the parts of the state., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Hemodynamic instability as a result of altered baroreflex mechanism is common in surgeries involving manipulation around the carotid sheath. We report a case in which hypertensive crisis was associated with laryngectomy during general anesthesia. Perioperative use of vasoactive agents such as alpha(2) agonists may help in maintaining hemodynamic stability in such procedures.

Central neuraxial block is associated with increased vagal tone. We report a patient who developed laryngospasm and stridor under spinal anaesthesia. This was treated successfully with i.v. atropine and fluids. We propose that the laryngospasm was secondary to increased vagal tone under the spinal anaesthetic. Such a manifestation of increased vagal tone under spinal anaesthesia has not been reported previously.

A new flavonol glycoside, characterized as 7-O-(6-O-benzoyl-beta-D-glucopyranosyl)-rutin (1), has been isolated from the leaves of Canthium dicoccum. Detailed 1H COSY, HSQC, HMBC and TOCSY NMR as well as positive and negative electrospray MS and MS/MS data have been provided for the new compound.