Advances in Pharmacology of Isatin and its Derivatives: A Review

Isatin (1H-indole-2,3-dione), an indole derivative of plant origin, is involved in many pharmacological activities like antiallergic, antimalarial, antiviral and antimicrobial; isatin and its derivatives have been found to show promising results against various cancer cell lines. Isatin is a versatile precursor for many biologically active molecules and its diversified nature makes it a versatile substrate for further modifications. This review provides a brief overview on the recent advances and future perspectives on pharmacological aspects of isatin and its derivatives reported in the last decade.Keywords: Isatin, Anticancer, Antimicrobial, Monoamine oxidase, Antivira

Stability analysis of Prey- Predator Model with Holling Type-II Response

In this paper we investigate the dynamics of prey-predator model of holling type II response function. The system is described by a system of ordinary differential equations. The boundedness properties, long term behaviour of the system, equilibrium points are identified. Local stability analysis is discussed at each of its equilibrium points. Global stability is studied by constructing suitable Lyapunov’s function. We proved that the system is both locally and globally asymptotically stable. Further Numerical simulation is performed and in support of analytical study

IN VITRO ANTHELMINTIC ACTIVITY OF AQUEOUS AND METHANOLIC EXTRACTS OF OLDENLANDIA UMBELLATA

Objective: The present study was carried out to evaluate the in vitro anthelmintic activity of aqueous and methanolic extracts of Oldenlandia umbelata against Pheretima posthuma. Methods: Three different concentrations, each of crude alcoholic and aqueous extract (10, 50,100 mg/ml in distilled water) were prepared and six worms (same type) were placed in it. Observations were made for the time taken to cause paralysis and death of the individual worms. Mean time for the paralysis (P) in min was noted when no movement of any sort could be observed,except when the worm was shaken vigorously; time of death (D) in min was recorded after ascertaining the worms neither moved when shaken vigorously nor when dipped in warm water (50°C). Piperazine citrate (10mg/ml) was included as reference compounds. Results: The extracts of Oldenlandia umbelata not only demonstrated paralysis, but also caused death of worms, especially at higher concentration of 100 mg/ml in shorter time as compared to reference drug Piperazine citrate. Conclusion: In present statement methanolic and aqueous extracts of plant of Oldenlandia umbelata was investigated for their anthelmintic activity against Pheretima posthuma. Various concentrations were used in the bioassay, which involved paralysis and death time of the worms. Both the extracts showed significant anthelmintic activity

Phosphoinositide 3-Kinase p110 Delta Differentially Restrains and Directs Naïve Versus Effector CD8⁺ T Cell Transcriptional Programs

Phosphoinositide 3-kinase p110 delta (PI3K p110δ) is pivotal for CD8+ T cell immune responses. The current study explores PI3K p110δ induction and repression of antigen receptor and cytokine regulated programs to inform how PI3K p110δ directs CD8+ T cell fate. The studies force a revision of the concept that PI3K p110δ controls metabolic pathways in T cells and reveal major differences in PI3K p110δ regulated transcriptional programs between naïve and effector cytotoxic T cells (CTL). These differences include differential control of the expression of cytolytic effector molecules and costimulatory receptors. Key insights from the work include that PI3K p110δ signalling pathways repress expression of the critical inhibitory receptors CTLA4 and SLAMF6 in CTL. Moreover, in both naïve and effector T cells the dominant role for PI3K p110δ is to restrain the production of the chemokines that orchestrate communication between adaptive and innate immune cells. The study provides a comprehensive resource for understanding how PI3K p110δ uses multiple processes mediated by Protein Kinase B/AKT, FOXO1 dependent and independent mechanisms and mitogen-activated protein kinases (MAPK) to direct CD8+ T cell fate

Exploring the Determinants of Digital Content Adoption By Academics: The Moderating Role of Environmental Concerns and Price Value

The study investigates the underlying motives facilitating users’ continuance intention for digital content in academic settings. Extending the expectation confirmation model of IS continuance (ECM-ISC), the study proposes a conceptual model by incorporating personal and technological antecedents of users’ continuance intention for digital content. In addition, users’ environmental concerns and price value are considered as potential moderators in the relationship between their satisfaction and continuance intention for digital content. An online survey was used to collect data from 311 digital content users of a large public university in Saudi Arabia. Structural equation modeling was used to test the relationships in the conceptual model. The results obtained from SmartPLS 3.2 confirm that compatibility, convenience, self-efficacy, and facilitating conditions are the predictors of confirmation and usefulness of digital content. The confirmation of expectations and perceived usefulness result in greater satisfaction with the digital content, which in turn leads to users’ continuance intention. In addition, the article provides empirical evidence for the impact of environmental concerns on the satisfaction–continuance intention relationship, thus opening a novel research debate. The study is expected to offer new insights both for academicians and managers of digital content

Determinants of response at 2 months of treatment in a cohort of Pakistani patients with pulmonary tuberculosis

Mycobacterium tuberculosis infection continues to be a major global challenge. All patients with pulmonary tuberculosis are treated with a standard 6-month treatment regimen. Historical data suggest that even with shortened treatment, most patients achieve long-term remission. Risk stratification is a goal for reducing potentially toxic prolonged treatment. This study aimed to determine the factors associated with the early clearance of sputum acid-fast bacilli (AFB). A total of 297 freshly diagnosed patients with pulmonary tuberculosis were included and enrolled in this study. Information related to their ethno-demographic and anthropometric characteristics was collected. We also assessed their complete blood counts, and blood iron, folate, and vitamin B12 levels. We found that the presence of higher levels of acid-fast bacilli (AFB) in diagnostic sputum microscopy was the single most significant prognostic factor associated with early clearance of sputum AFB after 2 months of treatment. All of our patients achieved treatment success after 6 months of treatment and were disease free. Our results support the data obtained from previous studies indicating that AFB clearance at 2 months is unlikely to be a clinically useful biomarker or indicator for therapeutic stratification. Furthermore, demographic, anthropometric, and nutritional factors are not clinically useful biomarkers

Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies

Sequence variants at the TERT-CLPTM1L locus in chromosome 5p have been recently associated with disposition for various cancers. Here we show that this locus including the gene encoding the telomerase reverse-transcriptase TERT at 5p13.33 is rarely but recurrently targeted by somatic chromosomal translocations to IGH and non-IG loci in B-cell neoplasms, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. In addition, cases with genomic amplification of TERT locus were identified. Tumors bearing chromosomal aberrations involving TERT showed higher TERT transcriptional expression and increased telomerase activity. These data suggest that deregulation of TERT gene by chromosomal abnormalities leading to increased telomerase activity might contribute to B-cell lymphomagenesis

Differential Requirement for Utrophin in the Induced Pluripotent Stem Cell Correction of Muscle versus Fat in Muscular Dystrophy Mice

Duchenne muscular dystrophy (DMD) is an incurable degenerative muscle disorder. We injected WT mouse induced pluripotent stem cells (iPSCs) into mdx and mdx∶utrophin mutant blastocysts, which are predisposed to develop DMD with an increasing degree of severity (mdx <<< mdx∶utrophin). In mdx chimeras, iPSC-dystrophin was supplied to the muscle sarcolemma to effect corrections at morphological and functional levels. Dystrobrevin was observed in dystrophin-positive and, at a lesser extent, utrophin-positive areas. In the mdx∶utrophin mutant chimeras, although iPSC-dystrophin was also supplied to the muscle sarcolemma, mice still displayed poor skeletal muscle histopathology, and negligible levels of dystrobrevin in dystrophin- and utrophin-negative areas. Not only dystrophin-expressing tissues are affected by iPSCs. Mdx and mdx∶utrophin mice have reduced fat/body weight ratio, but iPSC injection normalized this parameter in both mdx and mdx∶utrophin chimeras, despite the fact that utrophin was compromised in the mdx∶utrophin chimeric fat. The results suggest that the presence of utrophin is required for the iPSC-corrections in skeletal muscle. Furthermore, the results highlight a potential (utrophin-independent) non-cell autonomous role for iPSC-dystrophin in the corrections of non-muscle tissue like fat, which is intimately related to the muscle

Alzheimer's “Prevention” vs. “Risk Reduction”: Transcending Semantics for Clinical Practice

The terms “prevention” and “risk reduction” are often used interchangeably in medicine. There is considerable debate, however, over the use of these terms in describing interventions that aim to preserve cognitive health and/or delay disease progression of Alzheimer's disease (AD) for patients seeking clinical care. Furthermore, it is important to distinguish between Alzheimer's disease prevention and Alzheimer's dementia prevention when using these terms. While prior studies have codified research-based criteria for the progressive stages of AD, there are no clear clinical consensus criteria to guide the use of these terms for physicians in practice. A clear understanding of the implications of each term will help guide clinical practice and clinical research. The authors explore the semantics and appropriate use of the terms “prevention” and “risk reduction” as they relate to AD in clinical practice

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response