Decoding halal and jhatka slaughter: novel insights into welfare and protein biomarkers in slow-growing broiler chicken.

BACKGROUND: The first evidence of blood biochemical and proteomic changes in slow-growing broiler chicken subjected to ritual slaughter like halal (HS) and jhatka (JS) without stunning and commercial slaughter with electrical stunning (ES) was decoded. RESULTS: Significant stress indicators like cortisol and triiodothyronine were markedly elevated in JS birds, whereas increased (P < 0.05) levels of lactate dehydrogenase and creatine kinase were observed in JS and ES birds. Two-dimensional gel electrophoresis coupled to MALDI-TOF MS elucidated the overabundance of glyceraldehyde-3-phosphate dehydrogenase and l-lactate dehydrogenase that are positively correlated with stress in JS broilers. Bioinformatic analysis explored the multifaceted landscape of molecular functions. CONCLUSION: The study has uncovered that ritual slaughter performed without stunning against commercial slaughter with ES practices elicit varying levels of stress as evident from blood biochemistry and novel protein markers. © 2024 Society of Chemical Industry.

CTAB-Assisted Synthesis of FeNi Alloy Nanoparticles: Effective and Stable Electrocatalysts for Urea Oxidation Reactions.

Development of highly efficient electrocatalysts for treating urea-rich wastewater is an important problem in environmental management and energy production. In this work, an iron-nickel alloy (Fe-Ni alloy) was synthesized via soft-template cetyltrimethylammonium bromide (CTAB)-assisted precipitation using low-temperature calcination. The as-synthesized nanoalloy was characterized by X-ray diffraction (XRD), which revealed the formation of a face-centered cubic (FCC) structure of the Fe-Ni alloy; field emission-scanning electron microscopic (FE-SEM) analysis revealed the spherical shape of the Fe-Ni alloy; high-resolution transmission electron microscopy (HR-TEM) revealed the average size to be ∼33.09 nm; and X-ray photoelectron spectroscopy (XPS) showed the presence of Fe, Ni, C, and O components and their chemical composition and valence states in the Fe-Ni alloy. The electrochemical urea oxidation reaction (UOR) was investigated by conducting linear sweep voltammetry (LSV) tests on the synthesized electrocatalysts with different Ni/Fe ratios in alkaline electrolytes with urea. The potential required to reach a current density of 10 mA cm-2 is 1.27 V vs RHE, which demonstrates the higher electrochemical activity of the Fe-Ni alloy compared to other individual compounds. This could be due to CTAB which improved the structural stability and synergetic and electronic effects in the nanoscale. This study will further contribute to renewable energy generation technology with long-term energy sustainability and also opens up great potential for reducing water pollution.

Traditional halal meat production without stunning versus commercial slaughter with electrical stunning of slow-growing broiler chicken: impact on meat quality and proteome changes.

Impact of traditional halal meat production without stunning (NST) and commercial slaughter with electrical stunning (ST) of 100 slow-growing broiler chicken on blood plasma and different biochemical, enzymatic, hormonal, meat quality, and proteomic changes was evaluated. The results revealed lower (P < 0.05) postmortem pH values and higher redness (a*) scores for ST samples relative to NST group. Myofibrillar fragmentation index and bleeding efficiency (%) were lower (P < 0.05) in ST compared to NST samples. The ST group had higher (P < 0.05) creatinine, total protein, alanine aminotransferase (ALT), and triiodothyronine (T3) than NST group, however, no difference (P > 0.05) in blood glucose, lactate dehydrogenase (LDH), creatine kinase (CK), thyroxine (T4), cortisol, and aspartate aminotransferase (AST) was observed relative to NST samples. The 2-dimensional gel electrophoresis (2-DE) coupled to MALDI-TOF MS of meat samples has identified 14 differentially abundant proteins between 2 groups. Proteins demonstrating positive correlation with stress namely adenylate kinase isoenzyme-1, Rho guanine nucleotide exchange factor (NST), and apolipoprotein A-I (ST) were overabundant. From the current study, it is concluded that electrical stunning of broilers prior to slaughter or traditional halal slaughter without stunning does not adversely affect the meat quality.

Trained immunity of alveolar macrophages enhances injury resolution via KLF4-MERTK-mediated efferocytosis.

Recent studies suggest that training of innate immune cells such as tissue-resident macrophages by repeated noxious stimuli can heighten host defense responses. However, it remains unclear whether trained immunity of tissue-resident macrophages also enhances injury resolution to counterbalance the heightened inflammatory responses. Here, we studied lung-resident alveolar macrophages (AMs) prechallenged with either the bacterial endotoxin or with Pseudomonas aeruginosa and observed that these trained AMs showed greater resilience to pathogen-induced cell death. Transcriptomic analysis and functional assays showed greater capacity of trained AMs for efferocytosis of cellular debris and injury resolution. Single-cell high-dimensional mass cytometry analysis and lineage tracing demonstrated that training induces an expansion of a MERTKhiMarcohiCD163+F4/80low lung-resident AM subset with a proresolving phenotype. Reprogrammed AMs upregulated expression of the efferocytosis receptor MERTK mediated by the transcription factor KLF4. Adoptive transfer of these trained AMs restricted inflammatory lung injury in recipient mice exposed to lethal P. aeruginosa. Thus, our study has identified a subset of tissue-resident trained macrophages that prevent hyperinflammation and restore tissue homeostasis following repeated pathogen challenges.

Utility of Transbronchial Cryobiopsy via Flexible Bronchoscope in Diagnosis of Isolated Pulmonary LCH: A Case Report.

Flexible bronchoscopes are increasingly being used in diagnostic and therapeutic medicine and have obviated the need for and risks associated with general anesthesia. Here the authors present the case of a 2-y-old girl who was diagnosed with isolated pulmonary Langerhans cell histiocytosis by histopathology; a lung biopsy sample was obtained using a cryoprobe via a flexible bronchoscope. The girl was brought in with complaints of loss of weight, appetite loss, and rapid breathing for the past 2 mo. Examination revealed hypoxia, tachypnea, clubbing with failure to thrive, and bilateral crepitations on auscultation. Imaging studies showed ground-glass opacities with multiple cystic lesions in both lungs. A preliminary diagnosis of LCH was made, and transbronchial cryobiopsy was done via a flexible bronchoscope. Histopathology confirmed the diagnosis with Cluster of differentiation 1a (CD1a) staining. A flexible bronchoscope can be a useful tool for obtaining lung biopsy samples using a cryoprobe in children.

Efficient design and analysis of secure CMOS logic through logic encryption.

Untrusted third parties and untrustworthy foundries highlighted the significance of hardware security in the present-day world. Because of the globalization of integrated circuit (IC) design flow in the semiconductor industry, hardware security issues must be taken to prevent intellectual property (IP) piracy. Logic encryption is an efficient method to protect circuits from IP piracy, reverse engineering, and malicious tampering of IC for Trojan insertion. Researchers have proposed many logic encryption methods, which lead to overhead in circuit design parameters such as area, power, and performance. This paper aims to bring a trade-off between these parameters, with security being the main key factor, and ensure the design metrics by proposing a novel transistor-level method of logic encryption for CMOS gates. Experimental results show that, on the usage of proposed encrypted key gates, the design overheads such as area, power, delay, and energy are reduced by an average of 42.94%, 37.37%, 26.79%, and 50.96%, respectively, over the existing logic encryption-based topologies.

Etiology of Hemoptysis in Children and Adolescents - Multicentric Retrospective Data (2012-2021) From Chennai.

OBJECTIVE: To analyze the etiology of hemoptysis in children and to correlate the severity of bleed with the etiology. METHODS: This retrospective multicentre study reviewed data from inpatient units of four tertiary care public and private sector pediatric hospitals in Tamil Nadu. Methods: Inpatient case records of children (aged 2 month-15 years) treated for hemoptysis at the four institutions between April, 2012 and March, 2021 were identified, after ethical clearance from respective institutions. Data of children with underlying known bleeding disorders like hemophilia or platelet abnormality were excluded from the study. Hemoptysis was categorized as mild, moderate and severe. RESULTS: Of the 73 children who had presented with hemoptysis during the study period, 60 (82.2%) children had mild, 9 (12.3%) had moderate and rest had severe hemoptysis. Idiopathic pulmonary hemorrhage was the most common cause of hemoptysis. The common causes of mild hemoptysis in children were idiopathic pulmonary hemorrhage (n=15, 25%), pulmonary tuberculosis (n=12, 20%) and pneumonia (n=8, 13.3%). Congenital airway anomalies and vascular anomalies were more likely to present with moderate to severe bleed. CONCLUSIONS: Etiology of hemoptysis is broad and categorizing them into mild, moderate and severe may give a clue about the possible etiology, there by restricting to the required investigations.

Mixed lineage kinase 3 and CD70 cooperation sensitize trastuzumab-resistant HER2+ breast cancer by ceramide-loaded nanoparticles.

Trastuzumab is the first-line therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but often patients develop acquired resistance. Although other agents are in clinical use to treat trastuzumab-resistant (TR) breast cancer; still, the patients develop recurrent metastatic disease. One of the primary mechanisms of acquired resistance is the shedding/loss of the HER2 extracellular domain, where trastuzumab binds. We envisioned any new agent acting downstream of the HER2 should overcome trastuzumab resistance. The mixed lineage kinase 3 (MLK3) activation by trastuzumab is necessary for promoting cell death in HER2+ breast cancer. We designed nanoparticles loaded with MLK3 agonist ceramide (PPP-CNP) and tested their efficacy in sensitizing TR cell lines, patient-derived organoids, and patient-derived xenograft (PDX). The PPP-CNP activated MLK3, its downstream JNK kinase activity, and down-regulated AKT pathway signaling in TR cell lines and PDX. The activation of MLK3 and down-regulation of AKT signaling by PPP-CNP induced cell death and inhibited cellular proliferation in TR cells and PDX. The apoptosis in TR cells was dependent on increased CD70 protein expression and caspase-9 and caspase-3 activities by PPP-CNP. The PPP-CNP treatment alike increased the expression of CD70, CD27, cleaved caspase-9, and caspase-3 with a concurrent tumor burden reduction of TR PDX. Moreover, the expressions of CD70 and ceramide levels were lower in TR than sensitive HER2+ human breast tumors. Our in vitro and preclinical animal models suggest that activating the MLK3-CD70 axis by the PPP-CNP could sensitize/overcome trastuzumab resistance in HER2+ breast cancer.

Albumin Nanoparticle Endocytosing Subset of Neutrophils for Precision Therapeutic Targeting of Inflammatory Tissue Injury.

The complex involvement of neutrophils in inflammatory diseases makes them intriguing but challenging targets for therapeutic intervention. Here, we tested the hypothesis that varying endocytosis capacities would delineate functionally distinct neutrophil subpopulations that could be specifically targeted for therapeutic purposes. By using uniformly sized (∼120 nm in diameter) albumin nanoparticles (ANP) to characterize mouse neutrophils in vivo, we found two subsets of neutrophils, one that readily endocytosed ANP (ANPhigh neutrophils) and another that failed to endocytose ANP (ANPlow population). These ANPhigh and ANPlow subsets existed side by side simultaneously in bone marrow, peripheral blood, spleen, and lungs, both under basal conditions and after inflammatory challenge. Human peripheral blood neutrophils showed a similar duality. ANPhigh and ANPlow neutrophils had distinct cell surface marker expression and transcriptomic profiles, both in naive mice and in mice after endotoxemic challenge. ANPhigh and ANPlow neutrophils were functionally distinct in their capacities to kill bacteria and to produce inflammatory mediators. ANPhigh neutrophils produced inordinate amounts of reactive oxygen species and inflammatory chemokines and cytokines. Targeting this subset with ANP loaded with the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, mitigated the effects of polymicrobial sepsis by reducing tissue inflammation while fully preserving neutrophilic host-defense function.

Novel daidzein molecules exhibited anti-prostate cancer activity through nuclear receptor ERß modulation, in vitro and in vivo studies.

Eight novel ERß selective daidzein analogues (NCE1-8) were synthesized and their anti-cancer activity was evaluated by in vitro and in vivo methods. Cytotoxicity study, Receptor binding studies, Luciferase assay, cMYC & Cyclin D1 expression and Caspase 3, 8 & 9 activities were measured to ascertain the anticancer activity and mechanism. Uterotropic, anti-androgenic and anti-tumour activities were performed in rodents. The results revealed that NCEs produced anti-prostate cancer activity in DU145, LNCaP and PC3 cell lines and 50% more active than genistein. NCEs was significantly down-regulated cMYC & Cyclin D1 genes and elevated caspase 3 & 9 levels and did not show any difference in uterotropic, anti-androgenic activities. The tumour weight was also reduced. The NCE 1 and 2 have shown ERß selectivity in receptor binding studies. Daidzein with methyl substitution at R or R1 position exhibited more ERß selectivity and could be considered as lead molecules for anti-prostate cancer activity.

Valproate usage in pregnancy: An audit from the Kerala Registry of Epilepsy and Pregnancy.

OBJECTIVE: This is an audit of the use of valproate (VPA) during pregnancy in women with epilepsy (WWE). METHODS: We identified all pregnancies exposed to VPA in the Kerala Registry of Epilepsy and Pregnancy between January 2010 and December 2019. Subjects' past usage of antiepileptic drugs (AEDs), seizure count before and during pregnancy, fetal outcome, and major congenital malformations (MCMs) were abstracted from the registry records. The presumed reason for usage of VPA was deducted from the clinical records. RESULTS: There were 221 pregnancies (17.75%) exposed to VPA (monotherapy, n = 149) during the audit period. The MCM rate for the completed pregnancies exposed to VPA was higher (n = 20, 10.36%) than that of VPA-unexposed pregnancies (n = 39, 4.96%). The relative risk for MCM with VPA exposure was 2.1 (95% confidence interval = 1.24-3.48, number needed to treat with VPA to result in MCM = 19). Reasons for using VPA during pregnancy (some women had more than one reason) were (1) VPA was the first AED prescribed and was effective (68, 29.06%), (2) other AEDs were ineffective (128, 54.70%), and (3) other AEDs were discontinued due to adverse effects (17, 7.28%). Other reasons (21, 8.97%) were (1) VPA was selected after the epilepsy classification was revised (3, 1.28%), (2) other AEDs were expensive (2, .85%), and (3) patient switched to VPA from other AEDs for unspecified reason (16, 6.83%). VPA was discontinued during pregnancy for 6 (2.71%) persons. Less than 10% of women were tried on lamotrigine or levetiracetam before switching to VPA. SIGNIFICANCE: Nine MCMs per thousand pregnancies can be avoided if VPA is not used in WWE. Safe and effective AEDs as alternatives to VPA are the need of the hour. Professional bodies and regulatory authorities need to implement updated guidelines on AED usage in girls and women.

Tungsten oxides: green and sustainable heterogeneous nanocatalysts for the synthesis of bioactive heterocyclic compounds.

Tungsten oxide (WO3) as an efficient heterogeneous catalyst was prepared via a simple hydrothermal route for the synthesis of a wide range of bioactive heterocyclic compounds. The present investigation deals with the rapid and low-cost synthesis of C-3-alkylated 4-hydroxycoumarin, chromene, and xanthene derivatives. WO3 nanorods (NRs) are successfully envisaged to catalyze desired transformations, demonstrating the wide range of their potential applications in catalysis. Synthetic transformation details, smallest catalytic amounts, excellent product yields, and plausible reaction mechanisms for the formation of these heterocyclic scaffolds are elicidated. As-prepared WO3 NRs are characterized to confirm their structural, chemical, and morphological parameters by X-ray diffraction, X-ray photoelectron spectroscopy, and field emission scanning electron microscopy measurements, respectively. We discuss the factors that govern the formation of products, and the active role of WO3 NRs, which are essential for the activation of substrates in the present study of thermal conditions. Herein, detailed synthesis and spectroscopic information of the prepared compounds are reported.

Induction of Antigen-Independent Proliferation of Regulatory T-Cells by TNF Superfamily Ligands OX40L and GITRL.

TNF receptor superfamily comprises many T-cell costimulatory receptors, including TNFRSF1, TNFRSF2, TNFRSF4 (OX40), TNFRSF9 (4-1BB), TNFRSF18 (GITR), and TNFRSF7 (CD27). Signaling through these costimulatory stimulatory receptors can promote conventional T-cell (Tconv) proliferation, and effector functions in an antigen-dependent manner. Thus, agonistic antibodies and ligands for OX40, 4-1BB, GITR, and CD27 have been tested for inducing T-cell-mediated antitumor responses in several cancers. However, recently emerging reports show critical role for TNFR signaling in regulatory T-cell (Treg) differentiation and expansion, which might suppress effector T-cell proliferation and functions. Here, we show preferential over expression of TNFR2, OX40, 4-1BB, and GITR in Treg cells over Tconv cells, and the ability of OX40L and GITRL to induce selective proliferation of Treg cells, but not Tconv cells, in an antigen-independent manner. We describe the standard protocols used for Affymetrix gene expression profiling, T-cell isolation, and Cell Trace Violet-based cell proliferation assay.

Acceptability and outcomes of foreskin preservation for phimosis: An Indian perspective.

AIM: Understanding the Indian perspective, effectiveness, and acceptability of prepuce conservation in children with phimosis. Circumcision is performed and recommended far too often for nonphysiological phimosis. Will a less radical approach be acceptable in the subcontinent? METHOD: A two-arm study with the first arm as KAP (knowledge, attitude, and practice) study (n = 502). The second arm recruited deserving boys (n = 47) with symptomatic phimosis (see inclusion criteria). Betamethasone ointment was applied twice daily over the foreskin and gently massaged to stretch the phimotic band. Those who failed were offered lateral preputioplasty or circumcision. Religious beliefs influence attitude and practice and these were looked at with subgroup analysis. RESULTS: Most (85%) knew that circumcision was not the only treatment for phimosis. Though many parents (93%) knew the importance of foreskin cleanliness, few practiced it. The success of the steroid application was 81% (n = 38/47). Eight underwent preputioplasty. Minor discomfort as morbidity was noted. All parents were able to completely retract the foreskin of their children by the end of one month and were happy about the cosmetic result. CONCLUSIONS: KAP data on foreskin health is not available in the subcontinent, and this is a landmark study. Religious belief and community identity play a strong role in decisions related to foreskin preservation. Prepuce hygiene and knowledge about the usefulness of the foreskin is poor. The combination of medical and surgical methods of conserving the prepuce was effective. A high rate of success and the non-mutilating cosmetic result of prepuce preservation were acceptable to these parents.

Bi2O3 Nanoparticles Decorated Carbon Nanotube: An Effective Nanoelectrode for Enhanced Electrocatalytic 4-Nitrophenol Reduction.

4-Nitrophenol (4-NP) is present in most industrial waste water resources as an organic pollutant, and is a highly toxic and environmentally hazardous pollutant. Herein, we report that bismuth oxide (Bi2O3) decorated multi-walled carbon nanotubes (Bi2O3@MWCNTs) are the most prominent electrocatalyst for 4-NP electroreduction in acidic conditions. The electrocatalyst is synthesized by a simple chemical reduction method using ethylene glycol as a capping agent. The synthesized Bi2O3@MWCNTs electrocatalyst has been well-characterized by Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy. Bi2O3@MWCNTs have a cubic structure which is confirmed by XRD. TEM imaging reveals Bi2O3 NPs are ~2 nm in size, are grown on MWCNTs and that these nanoparticles are active toward 4-NP electroreduction. The electrochemical studies by cyclic voltammetry measurements show that the Bi2O3@MWCNTs electrocatalyst can sense 4-NP at a very low potential i.e., -0.17 vs. saturated calomel electrode (SCE). Furthermore, electroanalytical parameters like scan rate and concentration dependence were studied with electrochemcial impedance spectroscopy (EIS) and the effect of pH on cathodic current was examined under experimental conditions. The lower limit of detection (LOD) was found to be 0.1 µM for the Bi2O3@MWCNTs nanomaterial and is excellent toward 4-NP. The present study has applications for reducing water pollution and for sorting out related issues.

Bismuth-Oxide-Decorated Graphene Oxide Hybrids for Catalytic and Electrocatalytic Reduction of CO2.

Global warming challenges are fueling the demand to develop an efficient catalytic system for the reduction of CO2 , which would contribute significantly to the control of climate change. Herein, as-synthesized bismuthoxide-decorated graphene oxide (Bi2 O3 @GO) was used as an electro/thermal catalyst for CO2 reduction. Bi2 O3 @GO is found to be distributed uniformly, as confirmed by scanning electron and transmission electron microscopic analysis. The X-ray diffraction (XRD) pattern shows that the Bi2 O3 has a ß-phase with 23.4 m2 g-1 BET surface area. Significantly, the D and G bands from Raman spectroscopic analysis and their intensity ratio (ID /IG ) reveal the increment in defective sites on GO after surface decoration. X-ray photoelectron spectroscopic (XPS) analysis shows clear signals for Bi, C, and O, along with their oxidation states. An ultra-low onset potential (-0.534 V vs. RHE) for the reduction of CO2 on Bi2 O3 @GO is achieved. Furthermore, potential-dependent (-0.534, -0.734, and -0.934 vs. RHE) bulk electrolysis of CO2 to formate provides Faradaic efficiencies (FE) of approximately 39.72, 61.48, and 83.00 %, respectively. Additionally, in time-dependent electrolysis at a potential of -0.934 versus RHE for 3 and 5 h, the observed FEs are around 84.20 % and 87.17 % respectively. This catalyst is also used for the thermal reduction of CO2 to formate. It is shown that the thermal reduction provides a path for industrial applications, as this catalyst converts a large amount of CO2 to formate (10 mm).

Enhanced oxygen evolution reaction on amine functionalized graphene oxide in alkaline medium.

Development of highly efficient oxygen evolution reaction (OER) electrocatalysts is a critical challenge in the cost-effective generation of clean fuels. Here, a metal-free tyramine functionalized graphene oxide (T-GO) electrocatalyst is proposed to use in alkaline electrolytes for enhanced OER. Moreover, the T-GO and GO nanomaterials are well characterized by SEM, XRD, FTIR, XPS and Raman spectroscopy. T-GO exhibits an electrocatalytic OER with a current density of 2 mA cm-2 at a low onset potential of ∼1.39 V and a small Tafel slope of about 69 mV dec-1 and GO exhibits an onset potential of 1.51 V and Tafel slope of about 92 mV dec-1. Additionally, the current stability and RRDE based diffusion controlled response of the T-GO electrocatalyst are outstanding compared to GO. This study establishes metal free T-GO as an efficient electrocatalyst for the OER and used for cathodic production of hydrogen as a counter reaction in the field of water splitting.

Graphene oxide-based electrochemical activation of ethionamide towards enhanced biological activity.

The electrochemical behavior of ethionamide (ETO) was investigated on GO (∼500 nm) using the linear sweep voltammetric (LSV) technique at the sweep rate of 10 mV s-1 in 1 M PBS buffer solution, and the characteristic anodic signal was examined at 0.240 V over the potential range of -0.4 to 1 V vs. SCE. However, linearity was observed with the increase in scan rate (2-300 mV s-1) and concentration of ETO (1 µM to 100 mM), suggesting that the process involved diffusion-controlled electron transfer. The results also exhibited excellent current and potential stability, limit of detection (LOD 1.33) and limit of quantification (LOQ 4.4) at optimized experimental conditions. This electrochemical oxidation method was successfully applied in the complete oxidation of ETO to its oxidized form, which was further confirmed by high resolution mass spectroscopy (HRMS) and Fourier transform infrared (FTIR) spectroscopic measurements. Interestingly, the comparative biological evaluation of ETO and ETO-O (oxidised form) showed good enhancement in the activity of oxidised ETO against some Gram-negative pathogens, such as E. aerogenes, S. abony, S. boydii, and E. coli.

In silico study directed towards identification of novel high-affinity inhibitors targeting an oncogenic protein: BRD4-BD1.

Bromodomain-containing protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) family of proteins. It epigentically regulates the transcription of growth-promoting genes and has become an attractive target for the development of anticancer and anti-inflammatory agents. In the current study, we performed an in silico screening of a small-molecule chemical library against the acetyl-lysine binding site of the first bromodomain (BD1) in BRD4 protein. Potential inhibitors identified through virtual screening were further studied through molecular dynamics simulations, water entrapment analysis and Molecular Mechanics (MM)/Poisson-Boltzmann surface area (PBSA) binding free energy calculations. Many of the identified compounds exhibit better G-score (-11.64 kcal∙mol-1 to -10.31 kcal∙mol-1) and predicted binding affinity (-9.66 kcal∙mol-1 to -6.63 kcal∙mol-1) values towards BRD4-BD1 than that of the reference compound (+)-JQ1. Molecular dynamics simulation studies show that in free-form BRD4 the reported conserved water molecules are not retained at their specific positoins due to flexibiliy in the ZA-loop. In BRD4-ligand complexes the number and positions of conserved water molecules depends on the bound ligand. Identified potential inhibitors bind stably at the acetyl-lysine binding pocket of BRD4 and form direct and water-mediated hydrogen bonds with higher occupancy which may contribute to ligand specificity towards BRD4-BD1. Further, through MM/PBSA we calculated the binding free energies of selected compounds, which shows that they have comparable energies to that of (+)-JQ1, while NSC744713 shows better binding free energy.

Phytochemical analysis and broad spectrum antimicrobial activity of ethanolic extract of Jasminum mesnyi Hance leaves and its solventpartitioned fractions.

Jasminum mesnyi Hance (yellow jasmine, Family Oleaceae) belongs to an important subclass of Jasminum family whose biological significance is under explored. The current study pertains to isolation of various solvent extracts fractions and their anti-bacterial effects on the Gram-positive and Gram-negative bacterial pathogens. Ethanolic extract of J. mesnyi Hance leaves was subjected to further partitioning using different solvents with increasing polarity to get different solvent fractions. Different extracts were analysed for their phytochemical constitutents and were evaluated for their antibacterial activity against a number of diseases causing bacteria. Diethylether fraction (DEF) showed remarkable inhibition of growth of Aeromonas hydrophila and Vibrio parahaemolyticus with inhibition zones of 17 and 19mm, respectively at 250 µg. On the other hand, the hexane fraction (HF) was found to be more effective against Gram- positive test bacterial pathogens (Bacillus anthracis and Bacillus subtilis) with inhibition zones of 19.6 mm and 17.5 mm, respectively. The phytochemical screening of different test fractions revealed the predominant presence of cardiac glycosides, sterols and terpenoids in DEF and HF, while Ethylacetate fraction (EAF) and methanol fractions (MF) were found rich in flavonoids and phenols with moderate amount of other reference metabolites.