Epigallocatechin-3-gallate therapeutic potential in human diseases: molecular mechanisms and clinical studies.

Green tea has garnered increasing attention across age groups due to its numerous health benefits, largely attributed to Epigallocatechin 3-gallate (EGCG), its key polyphenol. EGCG exhibits a wide spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, anticancer, and neuroprotective properties, as well as benefits for cardiovascular and oral health. This review provides a comprehensive overview of recent findings on the therapeutic potential of EGCG in various human diseases.

FDA-approved drugs as PIM-1 kinase inhibitors: A drug repurposed approach for cancer therapy.

PIM-1 kinase, a member of the Serine/Threonine kinase family, has emerged as a promising therapeutic target in various cancers due to its role in promoting tumor growth and resistance to conventional therapies. In this study, we employed a structure-based approach to screen 3800 FDA-approved drugs to discover potential inhibitors of PIM-1. After an initial selection of 50 candidates based on high docking scores, four drugs, stanozolol, alfaxalone, rifaximin, and telmisartan, were identified as strong PIM-1 binders, interacting with key residues in the ATP-binding pocket of the kinase.

Targeting tau in Alzheimer's and beyond: Insights into pathology and therapeutic strategies.

Tauopathies encompass a group of approximately 20 neurodegenerative diseases characterized by the accumulation of the microtubule-associated protein tau in brain neurons. The pathogenesis of intracellular neurofibrillary tangles, a hallmark of tauopathies, is initiated by hyperphosphorylated tau protein isoforms that cause neuronal death and lead to diseases like Alzheimer's, Parkinson's disease, frontotemporal dementia, and other complex neurodegenerative diseases. Current applications of tau biomarkers, including imaging, cerebrospinal fluid, and blood-based assays, assist in the evaluation and diagnosis of tauopathies.

Dorzolamide intermediates with potential anti-inflammatory activity.

Dorzolamide (DZD), a Carbonic anhydrase (CA) inhibitor clinically used to lower intraocular pressure, exhibits anti-inflammatory effects owing to the drug's ability to inhibit the TIR domain-containing adaptor protein (TIRAP)-mediated signalling in macrophages. Here, we investigated whether DZD intermediates also demonstrate any anti-inflammatory property like DZD but with a reduced inhibition of CA. We found that several intermediates of DZD show increased binding to TIRAP at the common interface of kinases, such as Protein kinase C-delta (PKCδ) and Bruton's tyrosine kinase (BTK).

Exploring PDK3 inhibition in lung cancer through drug repurposing for potential therapeutic interventions.

The pyruvate dehydrogenase kinase-3 (PDK3) plays an important role in the regulation of a variety of cancers, including lung, by inhibiting the pyruvate dehydrogenase complex (PDC), shifting energy production towards glycolysis necessary for cancer metabolism. In this study, we aimed to identify potential PDK3 inhibitors using a computer-based drug design approach. Virtual screening of the FDA-approved library of 3839 compounds was carried out, from which Bagrosin and Dehydrocholic acid appeared best due to their strong binding affinity, specific interactions, and potential biological characteristics, and thus were selected for further investigations.

Investigating gene expression datasets of hippocampus tissue to discover Alzheimer's disease-associated molecular markers.

Background: Alzheimer's disease (AD) is an advancing neurodegenerative disorder distinguished by the formation of amyloid plaques and neurofibrillary tangles in the human brain. Nevertheless, the lack of peripheral biomarkers that can detect the development of AD remains a significant limitation.

Objective: The main aim of this work was to discover the molecular markers associated with AD.

Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications.

Cell survival and death are intricately governed by apoptosis, a meticulously controlled programmed cell death. Apoptosis is vital in facilitating embryonic development and maintaining tissue homeostasis and immunological functioning. It is a complex interplay of intrinsic and extrinsic signaling pathways that ultimately converges on executing the apoptotic program.

Identifying potential inhibitors against galectin-3-binding protein (LGALS3BP) for therapeutic targeting of glioma.

Glioblastoma is one of the most lethal types of Gliomas, and its treatment greatly depends on the stage of its detection. Galactin-3-binding protein (LGALS3BP) serves as a novel circulatory biomarker for detecting glioma at an early stage. This protein is also responsible for metastasis, proliferative signaling, angiogenesis, and immune system evasion in the case of brain tumors.

Correction: Investigating the role of prognostic mitophagy-related genes in non-small cell lung cancer pathogenesis via multiomics and network-based approach.

[This corrects the article DOI: 10.1007/s13205-024-04127-y.].

Investigating the inhibitory potential of natural bioactive compounds against cyclin-dependent kinase 13: virtual high throughput screening and MD simulation studies to target CDK signaling.

Cyclin-dependent kinase 13 (CDK13) belongs to the cyclin-dependent kinase (CDK) family that is actively involved in transcription regulation and RNA splicing. CDK13 binds with its partner, cyclin K, to regulate several biological processes. CDK13 and cyclin K complex phosphorylates RNA pol II carboxyl-terminal domain (CTD) at several serine residues, creating transcription elongation.

Marine polysaccharides for antibiofilm application: A focus on biomedical fields.

Microbial pathogens such as bacteria and fungi form biofilms, which represent substantial hurdles in treating human illness owing to their adaptive resistance mechanism to conventional antibiotics. Biofilm may cause persistent infection in a variety of bodily areas, including wounds, oral cavity, and vaginal canal. Using invasive devices such as implants and catheters contributes significantly to developing healthcare-associated infections because they offer an ideal surface for biofilm formation.

Discovering novel inhibitors of RfaH from Klebsiella pneumoniae to combat antimicrobial resistance.

RfaH is a crucial protein involved in anti-termination of transcription, which is necessary for spreading virulence in certain types of bacteria, such as Klebsiella pneumoniae and Escherichia coli. RfaH works by interacting directly with RNA polymerase and ribosomes, which activates the production of certain components needed for the bacteria's survival. Targeting RfaH offers a novel approach to hindering bacterial transcription and virulence.

Targeting transcriptional regulatory protein RfaH with natural compounds to develop novel therapies against .

The growing threat of antibiotic-resistant infections demands novel treatment strategies. This study focuses on the transcriptional regulatory protein RfaH, a protein crucial for the bacteria's virulence by promoting gene expression for its capsule, cell wall, and pilus. As becomes resistant to existing antibiotics, targeting RfaH with specific inhibitors offers a promising alternative.

Exploring phytochemical inhibitors of protein kinase C alpha for therapeutic targeting of Alzheimer's disease.

Background: Alzheimer's disease (AD) is characterized by neurodegeneration linked to amyloid-β (Aβ) plaques and tau protein tangles. Protein kinase C alpha (PKCα) plays a crucial role in modulating amyloid-β protein precursor (AβPP) processing, potentially mitigating AD progression. Consequently, PKCα stands out as a promising target for AD therapy.

Iron homeostasis and neurodegeneration in the ageing brain: Insight into ferroptosis pathways.

Ageing is a major risk factor for various chronic diseases and offers a potential target for developing novel and broadly effective preventatives or therapeutics for age-related conditions, including those affecting the brain. Mechanisms contributing to ageing have been summarized as the hallmarks of ageing, with iron imbalance being one of the major factors. Ferroptosis, an iron-mediated lipid peroxidation-induced programmed cell death, has recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD).

Investigating pH-induced conformational switch in PIM-1: An integrated multi spectroscopic and MD simulation study.

PIM-1 is a Ser/Thr kinase, which has been extensively studied as a potential target for cancer therapy due to its significant roles in various cancers, including prostate and breast cancers. Given its importance in cancer, researchers are investigating the structure of PIM-1 for pharmacological inhibition to discover therapeutic intervention. This study examines structural and conformational changes in PIM-1 across different pH using various spectroscopic and computational techniques.

Identification of potential bioactive phytochemicals for the inhibition of platelet-derived growth factor receptor β: a structure-based approach for cancer therapy.

Platelet-derived growth factor receptor beta (PDGFRβ) belongs to the receptor tyrosine kinase (RTK) protein family and is implicated in several disorders such as hematopoietic, glial, and soft-tissue cancer, non-cancerous disorders, including skeletal defects, brain calcification, and vascular anomalies. The research on small molecule inhibitors targeting PDGFRβ in cancer treatment has seen promising developments, but significant gaps remain. PDGFRβ, receptor tyrosine kinase, is overexpressed in various cancers and plays an important role in tumor progression, making it a potential therapeutic target.

Novel prospects in targeting neurodegenerative disorders via autophagy.

Protein aggregation occurs as a consequence of dysfunction in the normal cellular proteostasis, which leads to the accumulation of toxic fibrillar aggregates of certain proteins in the cell. Enhancing the activity of proteolytic pathways may serve as a way of clearing these aggregates in a cell, and consequently, autophagy has surfaced as a promising target for the treatment of neurodegenerative disorders. Several strategies involving small molecule compounds that stimulate autophagic pathway of cell have been discovered.

Role of MTH1 in oxidative stress and therapeutic targeting of cancer.

Cancer cells maintain high levels of reactive oxygen species (ROS) to drive their growth, but ROS can trigger cell death through oxidative stress and DNA damage. To survive enhanced ROS levels, cancer cells activate their antioxidant defenses. One such defense is MTH1, an enzyme that prevents the incorporation of oxidized nucleotides into DNA, thus preventing DNA damage and allowing cancer to proliferate.

An insight into impact of nanomaterials toxicity on human health.

In recent years, advances in nanotechnology have significantly influenced electronics manufacturing, industrial processes, and medical research. Various industries have seen a surge in the use of nanomaterials. However, several researchers have raised the alarm about the toxicological nature of nanomaterials, which appear to be quite different from their crude forms.

Exploring the effects of 4-chloro-o-phenylenediamine on human fibrinogen: A comprehensive investigation via biochemical, biophysical and computational approaches.

Fibrinogen (Fg), an essential plasma glycoprotein involved in the coagulation cascade, undergoes structural alterations upon exposure to various chemicals, impacting its functionality and contributing to pathological conditions. This research article explored the effects of 4-Chloro-o-phenylenediamine (4-Cl-o-PD), a common hair dye component (IUPAC = 1-Chloro-3,4-diaminobenzene), on human fibrinogen through comprehensive computational, biophysical, and biochemical approaches. The formation of a stable ligand-protein complex is confirmed through molecular docking and molecular dynamics simulations, revealing possible interaction having a favorable -4.

Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics.

Alzheimer's disease (AD) is a significant neocortical degenerative disorder characterized by the progressive loss of neurons and secondary alterations in white matter tracts. Understanding the risk factors and mechanisms underlying AD is crucial for developing effective treatments. The risk factors associated with AD encompass a wide range of variables, including gender differences, family history, and genetic predispositions.

Aldehydes alter TGF-β signaling and induce obesity and cancer.

Obesity and fatty liver diseases-metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)-affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2 and Aldh2Sptbn1 mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE).