Pharmacological Features and Therapeutic Implications of Plumbagin in Cancer and Metabolic Disorders: A Narrative Review.

Plumbagin (PLB) is a naphthoquinone extracted from . In recent times, there has been a growing body of evidence suggesting the potential importance of naphthoquinones, both natural and artificial, in the pharmacological world. Numerous studies have indicated that PLB plays a vital role in combating cancers and other disorders.

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.

Investigating underlying molecular mechanisms, signaling pathways, emerging therapeutic approaches in pancreatic cancer.

Pancreatic adenocarcinoma, a clinically challenging malignancy constitutes a significant contributor to cancer-related mortality, characterized by an inherently poor prognosis. This review aims to provide a comprehensive understanding of pancreatic adenocarcinoma by examining its multifaceted etiologies, including genetic mutations and environmental factors. The review explains the complex molecular mechanisms underlying its pathogenesis and summarizes current therapeutic strategies, including surgery, chemotherapy, and emerging modalities such as immunotherapy.

The neuroprotective potential of phytochemicals in traumatic brain injury: mechanistic insights and pharmacological implications.

Traumatic brain injury (TBI) leads to brain damage, comprising both immediate primary damage and a subsequent cascade of secondary injury mechanisms. The primary injury results in localized brain damage, while the secondary damage initiates inflammatory responses, followed by the disruption of the blood-brain barrier, infiltration of peripheral blood cells, brain edema, and the release of various immune mediators, including chemotactic factors and interleukins. TBI disrupts molecular signaling, cell structures, and functions.

Insights into the preventive actions of natural compounds against Klebsiella pneumoniae infections and drug resistance.

Klebsiella pneumoniae is a type of Gram-negative bacteria that causes a variety of infections, including pneumonia, bloodstream infections, wound infections, and meningitis. The treatment of K. pneumoniae infection depends on the type of infection and the severity of the symptoms.

The role of serum and glucocorticoid-regulated kinase 1 in cellular signaling: Implications for drug development.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a ubiquitously expressed protein belonging to the Ser/Thr kinase family. It regulates diverse physiological processes, including epithelial sodium channel activity, hypertension, cell proliferation, and insulin sensitivity. Due to its significant role in the pathogenesis of numerous diseases, SGK1 can be exploited as a potential therapeutic target to address challenging health problems.

Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases.

Phytochemicals are abundantly occurring natural compounds extracted from plant sources. Rosmarinic acid (RA) is an abundant phytochemical of species with various therapeutic implications for human health. In recent years, natural compounds have gained significant attention as adjuvant and complementary therapies to existing medications for various diseases.

Structure-Based Identification of Natural Compounds as Potential RET-Kinase Inhibitors for Therapeutic Targeting of Neurodegenerative Diseases.

Background: Tyrosine-protein kinase receptor Ret (RET), a proto-oncogene, is considered as an attractive drug target for cancer and neurodegenerative diseases, including Alzheimer's disease (AD).

Objective: We aimed to identify potential inhibitors of RET kinase among natural compounds present in the ZINC database.

Methods: A multistep structure-based virtual screening approach was used to identify potential RET kinase inhibitors based on their binding affinities, docking scores, and interactions with the biologically important residues of RET kinase.

Therapeutic targeting of microtubule affinity-regulating kinase 4 in cancer and neurodegenerative diseases.

Microtubule affinity-regulating kinase 4 (MARK4) is a member of the Ser/Thr protein kinase family, phosphorylates the microtubule-connected proteins and plays a vital role in causing cancers and neurodegenerative diseases. This kinase modulates multiple signaling pathways, including mammalian target of rapamycin, nuclear factor-κB, and Hippo-signaling, presumably responsible for cancer and Alzheimer's. MARK4 acts as a negative controller of the Hippo-kinase cassette for promoting YAP/TAZ action, and the loss of MARK4 detains the tumorigenic properties of cancer cells.

Therapeutic Targeting of Regulated Signaling Pathways of Non-Small Cell Lung Carcinoma.

Non-small cell lung carcinoma (NSCLC) is the most common cancer globally. Phytochemicals and small molecule inhibitors significantly prevent varying types of cancers, including NSCLC. These therapeutic molecules serve as important sources for new drugs that interfere with cellular proliferation, apoptosis, metastasis, and angiogenesis by regulating signaling pathways.

Investigating MARK4 inhibitory potential of Bacopaside II: Targeting Alzheimer's disease.

Microtubule affinity regulating kinase 4 (MARK4) is known to hyperphosphorylate tau protein, which subsequently causes Alzheimer's disease (AD). MARK4 is a well-validated drug target for AD; thus, we employed its structural features to discover potential inhibitors. On the other hand, complementary and alternative medicines (CAMs) have been used for the treatment of numerous diseases with little side effects.

Therapeutic targeting of Huntington's disease: Molecular and clinical approaches.

Huntington's disease (HD) is an autosomal dominant ailment that affects a larger population. Due to its complex pathology operating at DNA, RNA, and protein levels, it is regarded as a protein-misfolding disease and an expansion repeat disorder. Despite the availability of early genetic diagnostics, disease-modifying treatments are still missing.

Investigating regulated signaling pathways in therapeutic targeting of non-small cell lung carcinoma.

Non-small cell lung carcinoma (NSCLC) is the most common malignancy worldwide. The signaling cascades are stimulated via genetic modifications in upstream signaling molecules, which affect apoptotic, proliferative, and differentiation pathways. Dysregulation of these signaling cascades causes cancer-initiating cell proliferation, cancer development, and drug resistance.

A review on regulation of cell cycle by extracellular matrix.

The extracellular matrix (ECM) is a network of structural proteins, glycoproteins and proteoglycans that assists independent cells in aggregating and forming highly organized functional structures. ECM serves numerous purposes and is an essential component of tissue structure and functions. Initially, the role of ECM was considered to be confined to passive functions like providing mechanical strength and structural identity to tissues, serving as barriers and platforms for cells.

Microtubule-affinity regulating kinase 4: A potential drug target for cancer therapy.

The human genome encodes more than 500 protein kinases that work by transferring the γ-phosphate group from ATP to serine, threonine, or tyrosine (Ser/Thr/Tyr) residues. Various kinases are associated with the onset of cancer and its further progression. The recent advancements in developing small-molecule kinase inhibitors to treat different cancer types have shown noticeable results in clinical therapies.

Structure-guided design and development of cyclin-dependent kinase 4/6 inhibitors: A review on therapeutic implications.

Cyclin-dependent kinase 6 (EC 2.7.11.

Therapeutic implications and clinical manifestations of thymoquinone.

Thymoquinone (TQ), a natural phytochemical predominantly found in Nigella sativa, has been investigated for its numerous health benefits. TQ showed anti-cancer, anti-oxidant, and anti-inflammatory properties, validated in various disease models. The anti-cancer potential of TQ is goverened by anti-proliferation, cell cycle arrest, apoptosis induction, ROS production, anti-metastasis and anti-angiogenesis, inhibition of cell migration and invasion action.

Identification of Phytoconstituents as Potent Inhibitors of Casein Kinase-1 Alpha Using Virtual Screening and Molecular Dynamics Simulations.

Casein kinase-1 alpha (CK1α) is a multifunctional protein kinase that belongs to the serine/threonine kinases of the CK1α family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders.

B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy.

Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer.

Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects.

Background: PIM kinases are well-studied drug targets for cancer, belonging to Serine/Threonine kinases family. They are the downstream target of various signaling pathways, and their up/down-regulation affects various physiological processes. PIM family comprises three isoforms, namely, PIM-1, PIM-2, and PIM-3, on alternative initiation of translation and they have different levels of expression in different types of cancers.

Potential therapeutic targets of Klebsiella pneumoniae: a multi-omics review perspective.

The multidrug resistance developed in many organisms due to the prolonged use of antibiotics has been an increasing global health crisis. Klebsiella pneumoniae is a causal organism for various infections, including respiratory, urinary tract and biliary diseases. Initially, immunocompromised individuals are primarily affected by K.

A review on the role of TANK-binding kinase 1 signaling in cancer.

TANK-binding kinase 1 (TBK1) regulates various biological processes including, NF-κB signaling, immune response, autophagy, cell division, Ras-mediated oncogenesis, and AKT pro-survival signaling. Enhanced TBK1 activity is associated with autoimmune diseases and cancer, suggesting its role in therapeutic targeting of interferonopathies. In addition, dysregulation of TBK1 activity promotes several inflammatory disorders and oncogenesis.

Aurora B kinase: a potential drug target for cancer therapy.

Background: Ensuring genetic integrity is essential during the cell cycle to avoid aneuploidy, one of the underlying causes of malignancies. Aurora kinases are serine/threonine kinase that play a vital role in maintaining the genomic integrity of the cells. There are three forms of aurora kinases in the mammalian cells, which are highly conserved and act together with several other proteins to control chromosome alignment and its equal distribution to daughter cells in mitosis and meiosis.

Mechanistic insights into the pathogenesis of neurodegenerative diseases: towards the development of effective therapy.

Neurodegeneration is a prevalent and one of the emerging reasons for morbidity, mortality, and cognitive impairment in aging. Dementia is one of such conditions of neurodegeneration, partially manageable, irreversible, and worsens over time. This review is focused on biological and psychosocial risk factors associated with Alzheimer's and Parkinson's diseases, highlighting the value of cognitive decline.