Design, synthesis and anticancer evaluation of 4-Substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as dual topoisomerase I and II inhibitors.

In this study, we herein report the design, synthesis, and anticancer assessment of a series of new 4-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines. The synthesis involved key intermediates such as the 2-aminoester derivative, which underwent a series of reactions to produce compounds 7a-7t. The optimized SAr reactions, utilizing microwave irradiation in DMF, led to high yields and efficient preparation of the desired compounds.

Biogenesis and functional implications of extracellular vesicles in cancer metastasis.

Extracellular vesicles (EVs) play a crucial role in the complex process of cancer metastasis by facilitating cellular communication and influencing the microenvironment to promote the spread and establishment of cancer cells in distant locations. This paper explores the process of EV biogenesis, explaining their various sources that range from endosomal compartments to plasma membrane shedding. It also discusses the complex mechanisms that control the sorting of cargo within EVs, determining their chemical makeup.

Corrigendum: Editorial: Mechanistic insight and therapeutic potential for the management of non-alcoholic steatohepatitis (NASH).

[This corrects the article DOI: 10.3389/fendo.2024.

2-(4-Bromobenzyl) tethered 4-amino aryl/alkyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-]pyrimidines: design, synthesis, anticancer assessment dual topoisomerase-I/II inhibition, and studies.

A series of 2-(4-bromobenzyl) tethered 4-amino aryl/alkyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-]pyrimidines (7a-7u) were designed, synthesized, characterized and screened against a panel of cancer cell lines. Compound 7a, in particular, emerged as a potent antiproliferative agent against FaDu cells (HTB-43) with an IC value of 1.73 μM.

MicroRNA signatures in neuroplasticity, neuroinflammation and neurotransmission in association with depression.

Depression is a multifactorial disorder that occurs mainly on account of the dysregulation of neuroplasticity, neurotransmission and neuroinflammation in the brain. In addition to environmental /lifestyle factors, the pathogenesis of disease has been associated with genetic and epigenetic factors that affect the reprogramming of normal brain function. MicroRNA (miRNAs), a type of non-coding RNAs, are emerging as significant players that play a vital role in the regulation of gene expression and have been extensively explored in neurodegenerative disorders.

Exploring multi-media geochemical relationships in the southeastern Amazonian basin: A way forward to define source and background levels of potentially toxic elements in lake sediments.

Understanding geochemical source-sink relationships is an important aspect for developing background values of potentially toxic elements (PTEs) in a lake basin. This approach was studied in the Araguaia belt of Amazonia, Brazil. A total of 96 sediments (from 13 lake cores LA1-LA13), 36 surface soils, and 19 catchment rocks were collected in 2022 and chemical analysis of these samples was performed in the fine fraction (< 177 μm) using XRF and ICP-MS.

Integrating Polygenic Risk Scores (PRS) for Personalized Diabetes Care: Advancing Clinical Practice with Tailored Pharmacological Approaches.

The rising global prevalence of diabetes poses a serious threat to public health, national economies, and the healthcare system. Despite a high degree of disease heterogeneity and advancing techniques, there is still an unclear diagnosis of patients with diabetes compounded by the array of long-term microvascular and macrovascular complications associated with the disease. In addition to environmental variables, diabetes susceptibility is significantly influenced by genetic components.

Algae a Potential Source in Cosmetics: Current Status, Challenges, and Economic Implications.

Recently, many studies have revealed the association between environmental stresses and skin disorders. Skin protects the inner body organs as a first line of defence against various environmental detriments. The physical, chemical, biological, and environmental stresses and internal factors, including reactive oxygen species, can lead to skin aging, laxity, wrinkles, dryness, and coarse texture.

Successful Aging across Middle vs High-Income Countries: An Analysis of the Role of eHealth Literacy Associated with Loneliness and Wellbeing.

Background And Objectives: "Successful aging" concerns the process of growing older while maintaining physical, cognitive, and social wellbeing, emphasizing independence for overall satisfaction and quality of life. We investigate the impact of e-health literacy on reducing loneliness and sustaining wellbeing during the pandemic, comparing middle- and high-income countries.

Research Design And Methods: Online surveys were conducted between April 4, 2020, and September 30, 2021, collecting responses (N=2091) from medium- and high-income countries in Europe, Asia, and North America.

Mechanism to disrupt ESCRT-mediated intracellular trafficking through Vps28-small molecules interaction: an in silico approach.

The ESCRT (Endosomal Sorting Complex Required for Transport) machinery comprising protein complexes ESCRT-0 to ESCRT-III and Vps4 plays a pivotal role in intracellular trafficking, a process of endocytosing cell surface proteins into the cell for various biological activities. The ESCRT protein complexes are sequentially assembled which interact amongst each other to form a functional ESCRT machinery. Deregulation of these events are shown to be involved in various disease development including tumor formation and viral infections.

Production and Characterization of Pomelo Albedo Powder Based Pasta: Physicochemical, Functional, Textural and Sensorial Attributes.

Background: Pomelo albedo peel byproducts are composed of many health-ben-eficial phytochemicals during processing. This study aimed to maximize the potential of incorporating pomelo albedo powder as a bioactive ingredient in pasta.

Methods: In the present study, pomelo albedo was fortified with pasta at five different con-centrations (0, 3, 6, 9, and 12%), and its effects on the antioxidant, functional, textural, and sensorial attributes of pasta were investigated.

Role of Flavonoids in Mitigating the Pathological Complexities and Treatment Hurdles in Alzheimer's Disease.

With the passage of time, people step toward old age and become more prone to several diseases associated with the age. One such is Alzheimer's disease (AD) which results into neuronal damage and dementia with the progression of age. The existing therapeutics has been hindered by various enkindles like less eminent between remote populations, affordability issues and toxicity profiles.

Guanylate binding protein1 alters expression of the poly I: C induced cytokines/chemokines and MAP kinases in macrophages.

Guanylate binding protein 1 (GBP1) is critical in the host's innate immune response against viral infections and inflammation. Therefore, this study explored the role of GBP1 poly I: C, a synthetic analog of double-stranded RNA that mimics viral infections-induced inflammation in macrophages. Stimulation of human macrophage THP-1 and mice macrophage RAW 264.

Autophagy-related gene BECN1 single nucleotide polymorphisms in diseases.

Autophagy is a cytoprotective process that operates within a cell to maintain cellular homeostasis. An array of multiple proteins is involved to mediate this conserved cellular process. Among these, Beclin 1 protein encoded by BECN1 gene plays a crucial role during the initiation of autophagy.

Sustainable protocol for Cu-catalysed A-coupling under solvent-free conditions.

A Cu-catalyzed three-component cascade reaction has been developed, involving -alkynylaryl aldehydes, terminal alkynes and aliphatic/aromatic amines or diamines. This diversity oriented methodology successfully delivered a rich library of 72 molecules in good to excellent yields (yields up to 99%) through the application of an A-coupling reaction. This method is green, straightforward to execute, requires a short reaction time (2 min-4 h), does not require solvents or harsh or inert conditions, can be performed in open air, and utilizes only a small amount of a cheap and readily available catalyst (2.

Shedding light on microglial dysregulation in Alzheimer's disease: exploring molecular mechanisms and therapeutic avenues.

Alzheimer's disease (AD) stands out as the foremost prevalent neurodegenerative disorder, characterized by a complex etiology. Various mechanisms have been proposed to elucidate its onset, encompassing amyloid-beta (Aβ) toxicity, tau hyperphosphorylation, oxidative stress and reactive gliosis. The hallmark of AD comprises Aβ and tau aggregation.

Antifungal peptides: Therapeutic potential and challenges before their commercial success.

Antifungal peptides (AFPs) are small cationic peptides that are found in a diverse range of taxa including bacteria, plants, mammals and insects. AFPs exhibit the strong antifungal activities against several pathogenic fungi, making them potential candidates for developing novel antifungal agents. AFP cause fungal cell death by rupturing the membranes of the fungal cell wall and inhibits the vital enzymes.

Role of the I/D Polymorphism in Selected Public Health-Associated Sporting Modalities: An Updated Systematic Review and Meta-Analysis.

Background: The I/D polymorphism has been suggested to be associated with multiple chronic diseases and sports modalities, which has public health implications for global populations and sport performance. This updated review aims to strengthen the association and identify sporting disciplines that are most influenced by the gene polymorphism using a meta-analysis approach.

Methods: Published studies on the association between the I/D polymorphism and elite endurance and power were collected until 15 June 2024.

Understanding Aβ peptide altered exosomal proteome and associated pathways linked with the Alzheimer's disease pathogenesis using human neuroblastoma SH-SY5Y Cells.

The central nervous system (CNS) involves a complex interplay of communications between the neurons and various glial cells, which is crucial for brain functions. The major interactomes are exosomes that transmit sundry molecules (DNA, miRNAs, and proteins) between the cells and thus alter cell physiology. Exosomes can act as neuroprotective or neurodegenerative agents depending on the microenvironment of cells secreting them.

Atypical cutaneous leishmaniasis: a new challenge to VL elimination in South-East Asia.

Visceral leishmaniasis (VL) caused by in South-East Asian endemic countries including India, Nepal and Bangladesh has been the primary focus of the ongoing VL elimination program. With a major reduction in VL cases resulting from the elimination program during the last two decades, the efforts are now focused on the challenges posed by potential reservoirs within the asymptomatic cases, HIV-co-infection VL cases and Post Kala-azar Dermal Leishmaniasis (PKDL) cases that continue to sustain the parasite transmission cycle in known and newer endemic zones. This article brings attention to a new potential parasite reservoir in the form of atypical cutaneous leishmaniasis (ACL) cases caused by novel genetic variants.

Sunflower mapping using machine learning algorithm in Google Earth Engine platform.

The sunflower crop is one of the most pro sources of vegetable oil globally. It is cultivated all around the world including Haryana, in India. However, its mapping is limited due to the requirement of huge computation power, large data storage capacity, small farm holdings, and information gap on appropriate algorithms and spectral band combinations.

Pathophysiological role of high mobility group box-1 signaling in neurodegenerative diseases.

Nucleocytoplasmic translocation of HMGB1 (high mobility group box-1) plays a significant role in disease progression. Several methods contribute to the translocation of HMGB1 from the nucleus to the cytoplasm, including inflammasome activation, TNF-α signaling, CRM1-mediated transport, reactive oxygen species (ROS), JAK/STAT pathway, RIP3-mediated p53 involvement, XPO-1-mediated transport, and calcium-dependent mechanisms. Due to its diverse functions at various subcellular locations, HMGB1 has been identified as a crucial factor in several Central Nervous System (CNS) disorders, including Huntington's disease (HD), Parkinson's disease (PD), and Alzheimer's disease (AD).