Sub-acute bisphenol A exposure induces proteomic alterations and impairs male reproductive health in mice.

Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no-observed-adverse-effect level (NOAEL) dose. The present study investigates the effects of a sub-acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC-MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano-LC Easy-nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry-based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility.

Augmenting the basis of lodging tolerance in wheat (Triticum aestivum) under natural and simulated conditions.

In wheat (Triticum aestivum ), canopy architecture, culm diameter and stem strength are the key providers of lodging tolerance. To better understand the lodging phenomenon and determine the best linked trait to lodging, a study of lodging resistance was conducted in both artificially-induced and natural lodging conditions. Various morphological, phenological and biochemical traits, such as acid detergent fibre, acid detergent lignin, cellulose and activity of lignin-synthesising enzymes (phenylalanine ammonia lyase and tyrosine ammonia lyase) were recorded. Anatomical features were also examined by light microscopy, using the Wiesner reaction. Genotype C306 demonstrated the highest susceptibility to lodging compared to other varieties due to its limited production of lignin-synthesising enzymes, as well as its taller plant height and narrower culms. The dwarf mutants (DM6 and DM7) have a stronger resistance against lodging because they have thick stems and a short plant canopy structure. The most suitable donors for lodging are semidwarf varieties (HD2967, DPW621-50, DBW88) because they have higher production of lignin and lignin-synthesising enzymes. Grey correlation analysis also confirmed the ability of these three genotypes to tolerate lodging. The genotypes studied were comprehensively ranked. The study also includes an effort towards the standardisation of lodging methodology under artificial conditions.

Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers.

To identify cancer-associated gene regulatory changes, we generated single-cell chromatin accessibility landscapes across eight tumor types as part of The Cancer Genome Atlas. Tumor chromatin accessibility is strongly influenced by copy number alterations that can be used to identify subclones, yet underlying cis-regulatory landscapes retain cancer type-specific features. Using organ-matched healthy tissues, we identified the "nearest healthy" cell types in diverse cancers, demonstrating that the chromatin signature of basal-like-subtype breast cancer is most similar to secretory-type luminal epithelial cells. Neural network models trained to learn regulatory programs in cancer revealed enrichment of model-prioritized somatic noncoding mutations near cancer-associated genes, suggesting that dispersed, nonrecurrent, noncoding mutations in cancer are functional. Overall, these data and interpretable gene regulatory models for cancer and healthy tissue provide a framework for understanding cancer-specific gene regulation.

The burden of tuberculosis among patients with non-small cell lung carcinoma in a tertiary care center.

BACKGROUND: Lung cancer and tuberculosis share similar risk factors, clinical spectrum, radiological features and it is difficult to differentiate but it is important to diagnose both conditions for targeted therapy and better outcome. AIMS: Our primary objective was to estimate the proportion of TB in primary biopsy proven non-small cell lung carcinoma (NSCLC) cases. MATERIAL & METHODS: This prospective observational study was conducted in the Departments of Medicine/Pulmonary Medicine/Medical Oncology and Microbiology at the All India Institute of Medical Sciences, New Delhi for a period of 2 years (January 2020-December 2021). Patients with biopsy proven, primary non-small cell lung cancer were recruited and sputum samples were subjected to microbiological investigations to confirm tuberculosis. Comparison was done in two groups of lung cancer patients with confirmed TB (Group A) and without confirmed tuberculosis (Group B). RESULTS: Total 75 patients with biopsy proven, primary NSCLC were recruited and 16 % (12/75) were diagnosed with confirmed TB. Adenocarcinoma (36.48 %) and Squamous cell carcinoma (33.44 %) were the two predominant histopathological subtypes of NSCLC. About 57 (76 %) of them were found to be in stage IV of Lung cancer at initial presentation itself (75 % in group A & 74.6 % in group B; p value < 0.80). A majority of patients (11/12 cases; 91 %) of group A were males with a mean age of 59 ± 7.5 years. The upper lobes of the lung were involved in 65 % (49/75) of the cases and showing a mass lesion on imaging (75 % in group A & 65 % in group B; p value < 0.52). Kaplan Meier survival revealed a median survival time of 11 months in subjects with only NSCLC and a median survival time of 4 months in the group with concomitant TB and NSCLC (p value < 0.44).

Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.

Transcription factor (TF) DNA-binding dynamics govern cell fate and identity. However, our ability to pharmacologically control TF localization is limited. Here we leverage chemically driven binding site restriction leading to robust and DNA-sequence-specific redistribution of PU.1, a pioneer TF pertinent to many hematopoietic malignancies. Through an innovative technique, 'CLICK-on-CUT&Tag', we characterize the hierarchy of de novo PU.1 motifs, predicting occupancy in the PU.1 cistrome under binding site restriction. Temporal and single-molecule studies of binding site restriction uncover the pioneering dynamics of native PU.1 and identify the paradoxical activation of an alternate target gene set driven by PU.1 localization to second-tier binding sites. These transcriptional changes were corroborated by genetic blockade and site-specific reporter assays. Binding site restriction and subsequent PU.1 network rewiring causes primary human leukemia cells to differentiate. In summary, pharmacologically induced TF redistribution can be harnessed to govern TF localization, actuate alternate gene networks and direct cell fate.

Correlation of Pseudocholinesterase Level with Clinical, Biochemical Parameters Including Cardiac Profile and the Outcome in Organophosphorus Poisoning.

BACKGROUND: Poisoning is a significant health hazard and a leading cause of morbidity and mortality worldwide. India, being a predominantly agrarian country, routinely employs organophosphate (OP) pesticides in farming, and they are readily available "over the counter." OPs exert their toxicity by interfering with the normal function of acetylcholine, an essential neurotransmitter throughout the autonomic and central nervous systems. Due to the limited availability of facilities and resources in health-care systems, and economically restraining patients, it is necessary to rely more on clinical features to assess the severity of poisoning and manage the condition properly. METHODOLOGY: It was a hospital-based prospective observational study that included patients aged >13 years in a tertiary care hospital. All patients were clinically evaluated based on their history and examination. The diagnosis was made based on characteristic clinical manifestations or evidence of exposure to organophosphorus compounds (corroborative evidence such as empty containers and the odor of gastric aspirates). Clinical severity was assessed and categorized according to the Peradeniya Organophosphorus Poisoning Scale (POP scale). A score of 0-3 is considered mild poisoning, 4-7 as moderate poisoning, and 8-11 as severe poisoning. RESULTS: Out of the 50 patients enrolled in the study, 17 (34.00%) were aged <20 years, 19 (38%) were in the 20-30 years age group, and 14 (28%) were aged >30 years. Ingestion is the only mode of exposure to poisoning. None of the patients had history of contact or inhalational exposure. Of the 50 cases, 12 (24.0%) were in the mild category, 26 (52.0%) in the moderate category, and 12 (24%) in the severe category on the POP grading. A comparison of the mean serum pseudocholinesterase, troponin-T, and pro-BNP levels with severity was performed. In mild OP poisoning, the mean serum PChE level was 2766.58 ± 1120.44; in moderate, it was 1969.35 ± 1330.07, and in severe, it was 701.83 ± 961.17. Pseudocholinesterase levels decreased progressively with increasing clinical severity from mild-to-severe cases, and this association was statistically significant (P < 0.001). Two-dimensional echocardiography screening done in all patients did not show any significant abnormalities. CONCLUSION: This study shows that serum PCE is reduced in OP poisoning and correlates with the clinical severity grading done by the POP scale and is also associated with an increase in the duration of intensive care unit stay. No significant evidence of direct cardiac injury was observed in this study. A low Glasgow Coma Scale score and an increased respiratory rate at presentation are associated with poor outcomes.

Résumé Contexte:L'empoisonnement est un risque important pour la santé et une cause principale de morbidité et de mortalité dans le monde. L'Inde, étant principalement pays agraire, utilise régulièrement des pesticides organophosphotés (OP) dans l'agriculture, et ils sont facilement disponibles «en vente libre¼. OPS exerce leur toxicité en interférant avec la fonction normale de l'acétylcholine, un neurotransmetteur essentiel à travers l'autonomie et le centre systèmes nerveux. En raison de la disponibilité limitée des installations et des ressources dans les systèmes de soins de santé, et de la contention économique des patients, il est nécessaire pour s'appuyer davantage sur les caractéristiques cliniques pour évaluer la gravité de l'empoisonnement et gérer correctement la condition.Méthodologie:c'était un Étude d'observation prospective basée à l'hôpital qui comprenait des patients âgés de> 13 ans dans un hôpital de soins tertiaires. Tous les patients étaient cliniquement évalué en fonction de leur histoire et de leur examen. Le diagnostic a été posé sur la base de manifestations cliniques caractéristiques ou de preuves de Exposition aux composés organophosphores (preuves corroborantes telles que les conteneurs vides et l'odeur des aspirations gastriques). Gravité clinique a été évalué et classé selon l'échelle d'empoisonnement de Peradeniya organophosphorus (échelle pop). Un score de 0 à 3 est considéré comme doux Empoisonnement, 4­7 comme empoisonnement modéré et 8-11 comme empoisonnement sévère.Résultats:Sur les 50 patients inscrits à l'étude, 17 (34,00%) étaient âgés de <20 ans, 19 ans (38%) dans le groupe d'âge de 20 à 30 ans et 14 (28%) étaient âgés de> 30 ans. L'ingestion est le seul mode d'exposition à empoisonnement. Aucun des patients n'avait des antécédents de contact ou d'inhalation. Sur les 50 cas, 12 (24,0%) étaient dans la catégorie légère, 26 (52,0%) Dans la catégorie modérée, et 12 (24%) dans la catégorie sévère sur le classement POP. Une comparaison de la pseudocholinestérase sérique moyenne, Les niveaux de troponine - T et pro-BNP avec gravité ont été réalisés. Dans l'empoisonnement à l'op léger, le taux de PCHE sérique moyen était de 2766,58 ± 1120,44; dans Modéré, c'était 1969.35 ± 1330,07, et en sévère, il était de 701,83 ± 961,17. Les niveaux de pseudocholinestérase ont diminué progressivement avec l'augmentation Gravité clinique des cas légers à sévère, et cette association était statistiquement significative ( P <0,001). Échocardiographie bidimensionnelle Le dépistage effectué chez tous les patients n'a montré aucune anomalie significative.Conclusion:cette étude montre que le PCE sérique est réduit en op empoisonnement et corréler avec le classement de gravité clinique effectué par l'échelle POP et est également associé à une augmentation de la durée de séjour de l'unité de soins intensifs. Aucune preuve significative de lésion cardiaque directe n'a été observée dans cette étude. Un score d'échelle de coma à faible Glasgow et un Une fréquence respiratoire accrue à la présentation est associée à de mauvais résultats.

Sternal Reconstruction with a Custom-Made 3D-Printed Titanium Neo-sternum Prosthesis After Resection for Primary Malignant Sternal Tumour.

Primary sternal tumours are rare. Most of them are malignant in nature. When localized, cure can be achieved by radical resection. However, it leaves a large bony defect in front of the heart that makes reconstruction a challenge. In this report, we describe our experience of sternal reconstruction using a custom-made 3D-printed titanium neo-sternum after en-bloc resection of sternal body and anterior ends of bilateral second to fifth ribs for chondrosarcoma.

Sustainable preparation of AuAg alloy@AgBr Janus nanoparticles via dissipative self-assembly for photocatalysis.

We report a facile synthesis of cetyltrimethylammonium bromide (CTAB) templated AuAg alloy@AgBr Janus-nanoparticles (JNPs) using a non-conventional top-down approach with precise control over symmetry breaking. The addition of AgNO3 to a micellar solution of CTAB results in micelle-stabilized AgBr colloids having excess Ag+ at the interstitial sites of AgBr. AgBr colloids undergo weak self-assembly supported by inter-micellar interactions. The interfacial disturbance of self-assembled colloids via electrostatic adsorption of AuCl4- or Au(OH)4- at the micelle-AgBr interface downsizes the colloids. This is followed by the growth of the AuAg phase onto AgBr resulting in AuAg alloy@AgBr JNPs via different reduction pathways (photoreduction or chemical reduction) in the presence of ascorbic acid. The prepared JNPs act as efficient visible light photocatalysts for the degradation of aqueous rhodamine B. Interestingly, the trapping of holes favors the photocatalytic efficiency. Furthermore, the JNPs have shown proficiency in inhibiting the growth of both Gram-positive and Gram-negative bacteria as compared to the commercial antibiotic kanamycin, with a very low MIC value of ∼35 µg ml-1. In this way, a new single-pot strategy for the controlled preparation of photo-catalytically active and antimicrobial AuAg alloy@AgBr JNPs governed by dissipative self-assembly is reported for the first time.

Identification of Fatty Acids, Amides and Cinnamic Acid Derivatives in Supercritical-CO2 Extracts of Cinnamomum tamala Leaves Using UPLC-Q-TOF-MSE Combined with Chemometrics.

Cinnamomum tamala leaf (CTL), also known as Indian bay leaf, is used all over the world for seasoning, flavoring, and medicinal purposes. These characteristics could be explained by the presence of several essential bioactive substances and lipid derivatives. In this work, rapid screening and identification of the chemical compounds in supercritical (SC)-CO2 extracts of CTL by use of UPLC-Q-TOF-MSE with a multivariate statistical analysis approach was established in both negative and positive mode. A total of 166 metabolites, including 66 monocarboxylic fatty acids, 52 dicarboxylic fatty acids, 27 fatty acid amides, and 21 cinnamic acid derivatives, were tentatively identified based on accurate mass and the mass spectrometric fragmentation pattern, out of which 142 compounds were common in all SC-CO2 extracts of CTL. Further, PCA and cluster hierarchical analysis clearly discriminated the chemical profile of analyzed extracts and allowed the selection of SC-CO2 extract rich in fatty acids, fatty acid amides, and other bioactive constituents. The result showed that the higher number of compounds was detected in CTL4 (300 bar/55 °C) extract than the other CTL extracts. The mono- and di-carboxylic fatty acids, fatty acid amides, and cinnamic acid derivatives were identified in CTL for the first time. UPLC-Q-TOF-MSE combined with chemometric analysis is a powerful method to rapidly screen the metabolite profiling to justify the quality of CTL as a flavoring agent and in functional foods.

Structure of the human heparan-α-glucosaminide N-acetyltransferase (HGSNAT).

Degradation of heparan sulfate (HS), a glycosaminoglycan (GAG) comprised of repeating units of N-acetylglucosamine and glucuronic acid, begins in the cytosol and is completed in the lysosomes. Acetylation of the terminal non-reducing amino group of α-D-glucosamine of HS is essential for its complete breakdown into monosaccharides and free sulfate. Heparan-α-glucosaminide N-acetyltransferase (HGSNAT), a resident of the lysosomal membrane, catalyzes this essential acetylation reaction by accepting and transferring the acetyl group from cytosolic acetyl-CoA to terminal α-D-glucosamine of HS in the lysosomal lumen. Mutation-induced dysfunction in HGSNAT causes abnormal accumulation of HS within the lysosomes and leads to an autosomal recessive neurodegenerative lysosomal storage disorder called mucopolysaccharidosis IIIC (MPS IIIC). There are no approved drugs or treatment strategies to cure or manage the symptoms of, MPS IIIC. Here, we use cryo-electron microscopy (cryo-EM) to determine a high-resolution structure of the HGSNAT-acetyl-CoA complex, the first step in the HGSNAT-catalyzed acetyltransferase reaction. In addition, we map the known MPS IIIC mutations onto the structure and elucidate the molecular basis for mutation-induced HGSNAT dysfunction.

Carcinoma Endometrium Coexisting in Huge Procidentia.

Surgery remains the gold standard treatment for endometrial cancer. Vaginal approach is suitable for candidates with low risk for lymph node metastasis or in elderly females with extensive comorbidities, especially when surgery is done for palliative purpose only. We herein describe a case of cancer endometrium in huge procidentia, managed by vaginal hysterectomy followed by hormonal therapy.

CBNAAT: An Emerging Xpert in Diagnosis of Head and Neck Tuberculosis.

Aims and Obctives: To compare FNAC, microscopy (ZN staining), histopathology and CBNAAT for diagnosis of head and neck tuberculosis, and to evaluate efficacy of CBNAAT in early diagnosis of tuberculosis in head and neck region. Materials and methods: This prospective study was carried out in the department of otorhinolaryngology, JLN Medical College and attached hospital, Ajmer from August 2020 to September 2022. Thorough history and clinical examination of all patients presented with neck swelling was done. All relevant investigations including chest x-ray, mantoux test, ESR, FNAC, ZN staining, CBNAAT and histopathology were done and their efficacy was compared. Results: Sensitivity and specificity of CBNAAT in detecting extra pulmonary tuberculosis was 85.19% and 91.30% respectively, and diagnostic accuracy was consistent with findings of FNAC and ZN staining (p < 0.001) for diagnosis of cervical lymphadenopathy. Conclusion: CBNAAT has a promising role in early diagnosis of head and neck tuberculosis as well as other cases of smear negative tuberculosis such as MDR TB and TB-HIV and is optimal for the diagnosis of lymph node tuberculosis and helps in early identification and initiation of treatment. Sensitivity of CBNAAT scored twice as high in comparison with microscopy thus doubling the proportion of rapid diagnoses with important effect on the patient's outcome.

Correlation of Internal Jugular Vein and Inferior Vena Cava Collapsibility Index with Direct Central Venous Pressure Measurement in Critically-ill Patients: An Observational Study.

Background and aims: Prompt assessments and quick replacement of intravascular fluid are critical steps to resuscitate hypovolemic patients. Intravascular volume assessment by direct central venous pressure (CVP) measurement is an invasive, time-consuming, and labor-intensive procedure. Nowadays, bedside ultrasound-guided volume assessment of the internal jugular vein (IJV) or inferior vena cava (IVC) is commonly employed as a proxy for direct CVP.Therefore, we examined the strength of association between CVP and collapsibility index (CI) of the IJV and IVC for evaluating the volume status of critically ill patients. Methods: Bedside USG-guided A-P diameter and cross-sectional area of the right IJV and IVC were measured, and their corresponding collapsibility indices were deduced. The results of the IJV and IVC indices were correlated with CVP. Results: About 60 out of 70 enrolled patients were analyzed. The baseline clinical parameters of patients are shown in Table 1. For CSA and AP diameter, the correlations between CVP and IJV-CI at 0° were r = -0.107 (p = 0.001) and r = -0.092 (p = 0.001). Correlations between CVP and IJV-CI at 30° for CSA and diameter, however, were (r = -0.109, p = 0.001) and (r = -0.117, p = 0.001), respectively. Table 2 depicts the correlation between CVP and IVC-CI r = -0.503, p = 0.001 for CSA and r = -0.452, p = 0.001 for diameter. Conclusion: The IVC and IJV collapsibility indices can be used in place of invasive CVP monitoring to assess fluid status in critically ill patients. How to cite this article: Kumar A, Bharti AK, Hussain M, Kumar S, Kumar A. Correlation of Internal Jugular Vein and Inferior Vena Cava Collapsibility Index with Direct Central Venous Pressure Measurement in Critically-ill Patients: An Observational Study. Indian J Crit Care Med 2024;28(6):595-600.

Bioactive metabolites identification of the foxnut and broken millet-based nutritional bar using HR-MS.

The by-products of the grain processing industry are a vital resource for the valorization methods in the food industry. In comparison to the whole grain, the broken kernels and seeds own similar nutrient and bioactive compounds having multifaceted health properties. This study aims to develop a nutritional bar by utilizing the by-products from barnyard millet and foxnut with added sweeteners. Furthermore, high-resolution mass spectrometry (HR-MS) metabolomics was carried out in positive and negative both ion modes to identify the major bioactive compounds formed in the matrix of the best-optimized valorized bar. The formulation of the bar having 15 % foxnut flour and the barnyard flour each, was elucidated highest rheological and sensory scores. A sum of 29 bioactive metabolites has been observed in the obtained metabolome. Major metabolites were palmitoyl serinol, glycitein, persin, bufagargarizin, apigenin, carvone, etc. covering a wide area in the mass spectrum. The therapeutic value of these compounds is heart health promotion, anti-inflammatory, anti-carcinogenic, anti-diabetic, anti-microbial, etc. This work highlights the bioactivity of the valorized nutritional bar employing robust and accurate tool of mass spectrometry. The developed snack is a functional food for the consumers.

MV CBCT based assessment of setup uncertainties and planning target volume margin in head and neck cancer.

Background: Set-up errors are an undesirable part of the radiation treatment process. The goal of online imaging is to increase treatment accuracy by reducing the set-up errors. This study aimed to determine the daily variation of patient set-up uncertainties and planning target volume (PTV) margins for head and neck cancer patients using pre-treatment verification by mega voltage cone-beam computed tomography (MV-CBCT). Materials and methods: This retrospective study was internal record base of head and neck (H&N) cancer patients treated with definitive radiotherapy, adjuvant radiotherapy, and hypo-fractionated radiotherapy at our institution since the implementation of HalcyonTM 2.0 machine (Varian, US). Errors collected from each patient setup were recorded and evaluated for each direction [medio-lateral (ML), supero-inferior (SI), antero-posterior (AP)] discretely. For each patient, the systematic error (∑) and random error (σ) were collected. Clinical target volume (CTV) to planning target volume (PTV) margin was calculated using International Commission on Radiation Units and Measurements (ICRU) 62 ( PTV margin = ( Σ 2 + σ 2 ) ), Stroom's (PTV margin = 2∑ + 0.7σ), and Van Herk's (PTV margin = 2.5∑ + 0.7σ) formula. Results: A total of 7900 pre-treatment CBCT scans of 301 patients were analyzed and a total of 23,000 error measurements in the ML, SI, and AP directions were recorded. For all of our H&N cancer patients, the CTV to PTV margin, calculated from the van Herk formula for the head and neck patients was 0.49 mm in the anteroposterior axis. Conclusions: An isometric PTV margin of 5 mm may be considered safe if daily imaging is not being done. In case daily online pretreatment imaging is being utilized, further reduction of PTV margin is possible.

Deep Angiomyxoma of the Knee: a Rare Case Report.

Background: Deep angiomyxoma (DAM) is a slow-growing benign tumor with high risk of local recurrence after surgical resection. Although DAM in a lower extremity is extremely rare, clinicians must be aware of its possible occurrence. Suspicion can be made based on clinical examination and radiological imaging but final diagnosis is confirmed on histopathological examination and immunohistochemistry. We intend to present an extremely rare case of DAM in the knee, managed successfully with marginal excision. Case Presentation: A 4-year-old male child presented with the complains of a painless, progressively increasing, soft, non-tender, and fluctuant swelling in his right knee. The plain radiograph showed a non-calcified soft-tissue swelling and MRI revealed a multi-loculated cystic lesion with multiple septations. A pre-operative diagnosis of a benign cystic lesion was made. It was managed by marginal excision of the tumor and a histological diagnosis of DAM was made. IHC staining showed positivity for SMA, CD34 and vimentin were focally positive, while desmin and calponin were negative. At 12 months of follow-up, the patient had a normal painless gait and full knee ROM, without any local recurrence. Conclusion: DAM is a rare tumor which is often misdiagnosed. In this report, we present a rare case of benign cystic lesion which turned out to be DAM on HPE of resected specimen. Marginal excision of this lesion revealed good outcomes with no recurrence until 12 months of final follow-up. With this, we conclude that surgical excision should be the gold standard in cases of DAM.

In-silico based Designing of benzo[d]thiazol-2-amine Derivatives as Anal-gesic and Anti-inflammatory Agents.

BACKGROUND: Benzo[d]thiazoles represent a significant class of heterocyclic com-pounds renowned for their diverse pharmacological activities, including analgesic and anti-inflammatory properties. This molecular scaffold holds substantial interest among medicinal chemists owing to its structural versatility and therapeutic potential. Incorporating the benzo[d]thiazole moiety into drug molecules has been extensively investigated as a strategy to craft novel therapeutics with heightened efficacy and minimized adverse effects. AIMS: The aim of the present research work was to design, synthesize and characterize the new benzo[d]thiazol-2-amine derivatives as potent analgesic and anti-inflammatory agents. MATERIALS AND METHODS: The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and Mass spectroscopy methods were used to characterize the structural properties of all 13 newly syn-thesized derivatives. The molecular properties of these newly synthesized derivatives were estimated to study the attributes of drug-like candidates. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Analgesic and anti-inflammatory activities of synthesized compounds were evaluated by us-ing albino rats. RESULTS: Findings of the research suggested that compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8andG10 showed lower binding affinity than Indometha-cin when docking was performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities was performed for synthesized compounds. DISCUSSION: Compounds G10 and G11 exhibited significant COX-1 and COX-2 enzyme in-hibitory action with an IC50 value of 5.0 and 10 µM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. Highest analgesic action was exhibited by derivative G11 and the compound G10 showed the highest anti-inflammatory response. Inhibition of COX may be considered as a mechanism of action of these compounds. CONCLUSION: It was concluded that synthesized derivatives G10 and G11 exhibited significant analgesic and anti-inflammatory effect; therefore, the said compounds may be subjected to further clinical investigation for establishing these as future compounds for the treatment of pain and inflammation.

Dissipation kinetics and the evaluation of dietary risks associated with deltamethrin, ethion, fenazaquin, and fenpropathrin on bell pepper (Solanum annuum L.).

Bell peppers, a globally significant crop, face infestations from various pests. In a study, bell peppers were treated with deltamethrin, ethion, fenazaquin, and fenpropathrin at recommended and double the doses, repeated twice with a 10-day interval. The QuEChERS method underwent validation for linearity, matrix match, accuracy, and precision in bell pepper matrices for residue analysis. The limit of detection for the tested pesticides on bell peppers was 0.01 mg/L, with a quantification limit of 0.05 mg/L. Recovery studies showed a range of 94.80% to 102.80%. Initial deposits of deltamethrin, ethion, fenazaquin, and fenpropathrin on bell peppers at recommended doses were 0.371, 1.237, 0.617, and 0.640 mg/L, respectively, and at double doses were 0.712, 1.945, 1.221, and 1.189 mg/L, respectively. Safe waiting periods of 10, 11, 10, and 8 days were suggested for deltamethrin, ethion, fenazaquin, and fenpropathrin, respectively. The corresponding half-lives for the pesticides were 1.96, 1.79, 2.06, and 1.69 days, all following first-order dissipation kinetics. Dietary risk assessment indicated Hazard Quotients (HQ) below 1 and Theoretical Maximum Daily Intake (TMDI) below Acceptable Daily Intake (ADI) and Maximum Permissible Intake (MPI) levels. Therefore, at their recommended doses, the pesticides were deemed safe for bell pepper cultivation.

Optimization and Characterization of an Ultra-Thermostable, Acidophilic, Cellulase-Free Xylanase from a New Obligate Thermophilic Geobacillus thermoleovorans AKNT10 and its Application in Saccharification of Wheat Bran.

Microbial xylanases are enzymes of great importance due to their wide industrial applications, especially in the degradation of lignocellulosic biomass into fermentable sugars. This study aimed to describe the production optimization and partial characterization of an ultra-thermostable, acidophilic, cellulase-free xylanase from an obligate thermophilic eubacterium Geobacillus thermoleovorans strain-AKNT10 (Ac.No. LT158229) isolated from a hot-spring of Puga Valley located at an altitude of 4419 m in Ladakh, India. The optimization of cultural conditions improved enzyme yield by 10.49-fold under submerged fermentation. The addition of 1% (w/v) xylose induced the enzyme synthesis by ~ 165 and 371% when supplemented in the fermentation medium containing wheat bran (WB) 1 and 3%, respectively. The supplementation of sucrose reduced the xylanase production by ~ 25%. Results of partial characterization exhibited that xylanase was optimally active at pH 6.0 and 100 °C. Enzyme retained > 75%, > 83%, and > 84% of activity at 4 °C for 28 days, 100 °C for 60 min, and pHs 3-8 for 60 min, respectively. An outstanding property of AKNT10-xylanase, was the retention of > 71% residual activity at extreme conditions (121 °C and 15 psi pressure) for 15 min. Enzymatic saccharification showed that enzyme was also capable to liberate maximum reducing sugars within 4-8 h under optimized conditions thus it could be a potential candidate for the bioconversion of lignocellulosic biomass as well as other industrial purposes. To the best of our knowledge, this is the first report on such an ultra-thermo-pressure-tolerant xylanase optimally active at pH 6 and 100 °C from the genus Geobacillus.