Laurus labs (India)

Abstract Background −1031 (T/C) and AA for − 308 (G/A) showing a higher risk for disease susceptibility (OR = 3.5 and 8.7, respectively) and severity (OR = 1.99 and 8.59, respectively). Elevated levels of all biochemical markers were significantly correlated with higher severity of disease. Haplotype analysis demonstrated that individuals with variants at both loci exhibited the highest risk (OR = 3.67) for COVID-19. Conclusion These findings suggest that TNF-α polymorphisms may serve as potential genetic markers for predicting COVID-19 susceptibility and progression in South Indian population.

ABSTRACT N‐Nitroso impurities have emerged as a critical concern in pharmaceutical development due to their potential genotoxic and carcinogenic risks, often interrupting clinical programs and affecting the quality of commercial drug products. In this study, a microwave‐assisted green synthetic approach was employed to efficiently generate N‐nitroso Tofacitinib, a key nitrosamine impurity associated with the Janus kinase (JAK) inhibitor Tofacitinib. The method enabled rapid conversion under mild conditions, offering a sustainable strategy for impurity synthesis. An extensive structural elucidation of the synthesized N‐nitroso Tofacitinib impurity (TCB Imp 2) namely 1‐((3R,4R)‐4‐methyl‐3‐(methyl(7H‐pyrrolo[2,3‐d]pyrimidin‐4‐yl)amino)piperidin‐1‐yl)‐3‐(nitroso‐l4‐azanylidyne)propan‐1‐one was carried out using advanced spectroscopic and spectrometric techniques 1D, 2D‐ 1 H NMR, 13 C NMR, 15 N NMR, infrared spectroscopy, and mass spectrometry. A key observation from this study is that nitrosation occurred selectively at the nitrile‐derived side chain rather than at the pyrrolic nitrogen of the core heterocycle, providing new insight into the reactivity and formation pathways of N‐nitrosamine drug substance–related impurities (NDSRIs) in Tofacitinib. Additionally, two other potential N‐nitroso impurities of Tofacitinib were synthesized and fully characterized, expanding the impurity knowledge base. This work enhances mechanistic understanding of nitrosation behavior in Tofacitinib, supports regulatory compliance, and provides high‐quality reference standards for impurity profiling within the generic pharmaceutical industry.

Background Retinoblastoma is an aggressive cancer whose majority of patients are infants and children below the age of five. Approximately 80% of the total patients of retinoblastoma reside in low-to-middle-income countries like India. Lack of public and medical awareness and the absence of significant and regular clinical trials to test and authenticate new potential treatments impede the process of treating retinoblastoma. Attempts have been made to establish an effective way to diagnose retinoblastoma early so that it can be controlled in time, but so far, no significant success has been documented on that front. Moreover, recent strategies include computational and informatics solutions to identify potential targets at a genetic level to alter the expression of defective proteins in human subjects. Aim The main aim of the current study is to unravel the potential targets of Retinoblastoma, an aggressive pediatric cancer, utilizing an in silico network biology approach. Methods In the present study, we have utilized the gene network analysis approach to identify hub genes that affect the expression in the human system. We developed the Protein – Protein Interaction network utilizing 158 genes extracted from the NCBI OMIM database and identified 15 key genes, which were then subjected to metascape analysis to identify pathways and processes that affect and prioritize genes based on their significance scores. We were able to identify the following target genes: RBBP4, TFDP1, and RBBP7. Result RBBP4, TFDP1, and RBBP7 were identified as the most novel target genes against retinoblastoma after gene network and enrichment analysis. Conclusion Our in-silico network analysis unveiled the intricate mechanisms behind the progression of retinoblastoma by dissecting 158 associated genes in humans. Thus, this work not only illuminates the underlying dynamics of the disease but also offers a promising avenue for intervention.

Introdução: A época de erupção dos terceiros molares inferiores pode coincidir com o apinhamento dos incisivos inferiores. O terceiro molar como um dos fatores etiológicos do apinhamento anteroinferior ainda não é completamente aceita e pode levar a tratamentos desnecessários e incerteza dos resultados do tratamento ortodôntico. Objetivo: Correlacionar o espaço retromolar e o apinhamento dentário anteroinferior. Material e Métodos: Foram avaliados 21 pacientes com maloclusão de classe I de Angle, que apresentavam radiografia cefalométrica em norma lateral e modelos de estudo de gesso. Foram coletadas informações sobre idade, sexo, etnia. Foram determinados o padrão de crescimento facial e a distância retromolar dos participantes por meio de análise da radiografia cefalométrica, o índice de irregularidade de Little foi calculado, a partir da análise de modelos, para determinar a severidade do apinhamento dentário. A radiografia panorâmica foi utilizada para avaliar a presença e a posição dos terceiros molares. Resultados: O padrão mesofacial foi o mais frequente (66,7%), seguido pelo braquifacial (33,3%). A maioria dos pacientes apresentavam apinhamento moderado (52,4%), seguido por apinhamento mínimo (28,6%). Não houve diferença estatisticamente significante no índice de Little considerando a tipologia facial. Não houve correlação entre o espaço retromolar e o índice de Little. Conclusão: Não há correlação significativa entre o espaço retromolar e apinhamento dentário, sugerindo que a presença do terceiro molar não tem influência no apinhamento anteroinferior.

A variety of sugar-fused chromanono pyrrolidines/pyrrolizidines/thiolizidines have been synthesized by intermolecular 1,3-dipolar cycloaddition reaction of azomethine ylides (generated from glucose aldehyde and different secondary amino acids) with various 3-arylidene chroman-4-ones as dipolarophiles. The solvent effect on the 1,3-dipolar cycloaddition reaction is also studied.

Abstract A general method for the preparation of heterocyclic prostaglandins with variations in the ω‐side chain is presented.

The compounds (IV), (V), and (VIII) are tested in vitro for their activity against the Gram-negative bacteria E.