Unraveling the potential contribution of DHHC2 in cancer biology via untargeted metabolomics.

DHHC-mediated protein-S-palmitoylation is recognized as a distinct and reversible lipid modification, playing a pivotal role in the progression and prevention of multiple diseases, including cancer and neurodegenerative disorders. Over the past decade, growing evidence indicates the crucial role of DHHC2 in preventing tumorigenesis by palmitoylation of various protein substrates. However, a comprehensive understanding of the specific impact of DHHC2 on cancer cell metabolic regulation remains unclear.

Recapitulating the potential contribution of protein S-palmitoylation in cancer.

Protein S-palmitoylation is a reversible form of protein lipidation in which the formation of a thioester bond occurs between a cysteine (Cys) residue of a protein and a 16-carbon fatty acid chain. This modification is catalyzed by a family of palmitoyl acyl transferases, the DHHC enzymes, so called because of their Asp-His-His-Cys (DHHC) catalytic motif. Deregulation of DHHC enzymes has been linked to various diseases, including cancer and infections.

Preclinical evaluation of engineered L-asparaginase variants to improve the treatment of Acute Lymphoblastic Leukemia.

Introduction: Escherichia coli l-asparaginase (EcA), an integral part of multi-agent chemotherapy protocols of acute lymphoblastic leukemia (ALL), is constrained by safety concerns and the development of anti-asparaginase antibodies. Novel variants with better pharmacological properties are desirable.

Methods: Thousands of novel EcA variants were constructed using protein engineering approach.

Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.

Extrapulmonary tuberculosis with a renal involvement can be a manifestation of a disseminated infection that requires therapeutic intervention, particularly with a decrease in efficacy of conventional regimens. In the present study, we investigated the therapeutic potency of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in the complex anti-tuberculosis treatment (ATT). A rabbit model of renal tuberculosis (rTB) was constructed by injecting of the standard strain Mycobacterium tuberculosis H37Rv into the cortical layer of the kidney parenchyma.

Identification of selective plant-derived natural carotenoid and flavonoids as the potential inhibitors of DHHC-mediated protein palmitoylation: an study.

Protein palmitoylation mediated by DHHCs is recognized as a distinct and reversible form of lipid modification connected with several health perturbations, including neurodegenerative disorders, cancer, and autoimmune conditions. However, the pharmacological characteristics of current pan-DHHC inhibitors, particularly their toxicity and off-target effects, have hindered their in-depth cellular investigations. The therapeutic properties of the natural compounds, with minimal side effects, allowed us to evaluate them as DHHC-targeting inhibitors.

4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells.

Epidermal growth factor receptor (EGFR)-targeted therapy has been proven vital in the last two decades for the treatment of multiple cancer types, including nonsmall cell lung cancer, glioblastoma, breast cancer and head and neck squamous cell carcinoma. Unfortunately, the majority of approved EGFR inhibitors fall into the drug resistance category because of continuous mutations and acquired resistance. Recently, autophagy has surfaced as one of the emerging underlying mechanisms behind resistance to EGFR-tyrosine kinase inhibitors (TKIs).

Exploring the antimicrobial potential of isoniazid loaded Cu-based metal-organic frameworks as a novel strategy for effective killing of .

Tuberculosis (TB) remains one of the most infectious pathogens with the highest human mortality and morbidity. Biofilm formation during () infection is responsible for bacterial growth, communication, and, most essentially, increased resistance/tolerance to antibiotics leading to higher bacterial persistence. Thus, biofilm growth is presently considered a key virulence factor in the case of chronic disease.

Chitosan-Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery.

The current study paves the way for improved chemotherapy by creating pH-responsive nanogels (NGs) ( and ) loaded with synthetic ruthenium(II) arene complexes to increase biological potency. NGs are fabricated by the conjugation of chitosan (CTS)-biotin biopolymers that selectively target the cancer cells as CTS has the pH-responsive property, which helps in releasing the drug in cancer cells having pH ∼ 5.5, and biotin provides the way to target the cancer cells selectively due to the overexpression of integrin.

20 years since the approval of first EGFR-TKI, gefitinib: Insight and foresight.

Epidermal growth factor receptor (EGFR) actively involves in modulation of various cancer progression related mechanisms including angiogenesis, differentiation and migration. Therefore, targeting EGFR has surfaced as a prominent approach for the treatment of several types of cancers, including non-small cell lung cancer (NSCLC), pancreatic cancer, glioblastoma. Various first, second and third generation of EGFR tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated effectiveness as an anti-cancer therapeutics.

Role of EGFR and FASN in breast cancer progression.

Breast cancer (BC) emerged as one of the life-threatening diseases among females. Despite notable improvements made in cancer detection and treatment worldwide, according to GLOBACAN 2020, BC is the fifth leading cancer, with an estimated 1 in 6 cancer deaths, in a majority of countries. However, the exact cause that leads to BC progression still needs to be determined.

Multifaceted Carbon Dots: toward pH-Responsive Delivery of 5-Fluorouracil for In Vitro Antiproliferative Activity.

The synthesis of smart hybrid material to assimilate diagnosis and treatment is crucial in nanomedicine. Herein, we present a simple and facile method to synthesize multitalented blue-emissive nitrogen-doped carbon dots . The as-prepared carbon dots show enhanced biocompatibility, small size, high fluorescence, and high quantum yield.

Epigenetic orchestration of host immune defences by Mycobacterium tuberculosis.

Being among the top 10 causes of adult deaths, tuberculosis (TB) disease is considered a major global public health concern to address. The human tuberculosis pathogen, Mycobacterium tuberculosis (Mtb), is an extremely competent and well-versed pathogen that promotes pathogenesis by evading the host immune systems through numerous tactics. Investigations revealed that Mtb could evade the host defense mechanisms by reconfiguring the host gene transcription and causing epigenetic changes.

Studies on anticancer properties with varying co-ligands in a Ru(II) arene benzimidazole system.

Recently in the field of chemotherapeutics, to combat the side effects of cisplatin, ruthenium complexes have been investigated extensively. In this work, a bidentate benzimidazole-based ligand, HL [HL = 2-(1-benzo[]imidazol-2-yl)-6-methoxyphenol], was utilized to obtain three Ru(II) arene complexes having a generalized formula [Ru(η--cym)(L)(X)] or [Ru(η--cym)(L)(X)] (where -cym = -cymene). The co-ligand X (X = (i) Cl, (ii) PPh = triphenyl phosphine, and (iii) PTA = 1,3,5-triaza-7-phosphaadamantane) was varied in order to study the effect it has on the antitumor activity of the compounds.

Detection of Peroxisomal Proteins During Mycobacterial Infection.

Peroxisomes are ubiquitous organelles with essential roles in lipid and reactive oxygen species (ROS) metabolism. They are involved in modulating the immune responses during microbial infection, thus having major impact on several bacterial and viral infectious diseases including tuberculosis. Intracellular pathogens such as Mycobacterium tuberculosis (M.

Dysbiosis of Gut Microbiota from the Perspective of the Gut-Brain Axis: Role in the Provocation of Neurological Disorders.

The gut-brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems.

Host-mycobacteria conflict: Immune responses of the host vs. the mycobacteria TLR2 and TLR4 ligands and concomitant host-directed therapy.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the most grievous infectious diseases with long-term morbidity and unpredicted mortality rates globally. Thus, understanding the host-pathogen interactions to develop potential drugs is the most focused area of research. Mtb has many antigens communicating with host cells via various pattern recognition receptors (PRRs).

Structure-based design and synthesis of a novel long-chain 4''-alkyl ether derivative of EGCG as potent EGFR inhibitor: and studies.

Herein, we report the discovery of a novel long-chain ether derivative of (-)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol as a potent EGFR inhibitor. A series of 4''-alkyl EGCG derivatives have been synthesized regio-selectively alkylating the 4'' hydroxyl group in the D-ring of EGCG and tested for their antiproliferative activities against high (A431), moderate (HeLa), and low (MCF-7) EGFR-expressing cancer cell lines. The most potent compound, 4''-C EGCG showed the lowest IC values across all the tested cell lines.

Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages.

() inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible deletion mutant of failed to induce peroxisome biogenesis, expression of the peroxisomal β-oxidation pathway intermediates (ACOX1, ACAA1, MFP2) in macrophages, resulting in reduced intracellular survival compared to the parental strain.

Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes.

inhibits autophagy to promote its survival in host cells. However, the molecular mechanisms by which inhibits autophagy are poorly understood. Here, we report a previously unknown mechanism in which phosphoribosyltransferase (PRT) inhibits autophagy in an mTOR, negative regulator of autophagy, independent manner by inducing histone hypermethylation (H3K9me2/3) at the and promoters by activating p38-MAPK- and EHMT2 methyltransferase-dependent signaling pathways.

Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema.

Identification and evaluation of immunogenic MHC-I and MHC-II binding peptides from Mycobacterium tuberculosis.

Due to several limitations of the only available BCG vaccine, to generate adequate protective immune responses, it is important to develop potent and cost-effective vaccines against tuberculosis (TB). In this study, we have used an immune-informatics approach to identify potential peptide based vaccine targets against TB. The proteome of Mycobacterium tuberculosis (Mtb), the causative agent of TB, was analyzed for secretory or surface localized antigenic proteins as potential vaccine candidates.

Mycobacterium tuberculosis EsxL induces TNF-α secretion through activation of TLR2 dependent MAPK and NF-κB pathways.

Mycobacterium tuberculosis (Mtb) employs distinct strategies to circumvent host immune responses during the infection process. Various Mtb cell-wall associated and secretory proteins are known to play a critical role in the orchestration of host innate immune responses through modulation of signaling pathways. Mtb genome encodes for 23 (EsxA-EsxW) proteins belonging to the ESAT-6 like family; however, most of them are functionally unknown.

Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibition: an analysis.

The sudden outburst of Coronavirus disease (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a massive threat to global public health. Currently, no therapeutic drug or vaccine exists to treat COVID-19. Due to the time taking process of new drug development, drug repurposing might be the only viable solution to tackle COVID-19.

Differential Roles of the Calcium Ion Channel TRPV4 in Host Responses to Mycobacterium tuberculosis Early and Late in Infection.

Mycobacterium tuberculosis subverts host immunity to proliferate within host tissues. Non-selective transient receptor potential (TRP) ion channels are involved in host responses and altered upon bacterial infections. Altered expression and localization of TRPV4 in macrophages upon virulent M.