Cellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation.

Fas-associated death domain (FADD) is an adaptor protein that predominantly transduces the apoptosis signal from the death receptor (DR) to activate caspases, leading to the initiation of apoptotic signaling and the coordinated removal of damaged, infected, or unwanted cells. In addition to its apoptotic functions, FADD is involved in signaling pathways related to autophagy, cell proliferation, necroptosis, and cellular senescence, indicating its versatile role in cell survival and proliferation. The subcellular localization and intracellular expression of FADD play a crucial role in determining its functional outcomes, thereby highlighting the importance of spatiotemporal mechanisms and regulation.

Insights of Endocytosis Signaling in Health and Disease.

Endocytosis in mammalian cells is a fundamental cellular machinery that regulates vital physiological processes, such as the absorption of metabolites, release of neurotransmitters, uptake of hormone cellular defense, and delivery of biomolecules across the plasma membrane. A remarkable characteristic of the endocytic machinery is the sequential assembly of the complex proteins at the plasma membrane, followed by internalization and fusion of various biomolecules to different cellular compartments. In all eukaryotic cells, functional characterization of endocytic pathways is based on dynamics of the protein complex and signal transduction modules.

Higher BCG-induced trained immunity prevalence predicts protection from COVID-19: Implications for ongoing BCG trials.

Endeavors to identify potentially protective variables for COVID-19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID-19 impact on populations to their Bacillus-Calmette-Guérin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID-19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous 'trained immunity' (TI) conferred by exposure to spp.

Phosphodiesterase 5 inhibitor sildenafil potentiates the antitumor activity of cisplatin by ROS-mediated apoptosis: a role of deregulated glucose metabolism.

Cyclic nucleotide phosphodiesterase 5 (PDE5) has been recently identified to play a crucial role in the progression of many cancers. PDE5 promotes tumorigenesis by dysregulating various cellular processes such as proliferation, apoptosis, angiogenesis, and invasion and migration. Interestingly, multiple studies have reported the promising chemosensitizing potential of PDE5 inhibitor sildenafil in breast, colon, prostate, glioma, and lung cancers.

Evaluation of antimitotic activity of herbal extracts using plant-based model systems and their cytotoxic potential against human colon carcinoma cells.

Objective: The aim of this study was to screen plant extracts for antimitotic activity using Vigna radiata germination inhibition assay, followed by Allium cepa root tip assay and evaluation of their cytotoxic potential on colon carcinoma (HCT-116) cell lines.

Subjects And Methods: Aqueous extracts of Aconitum heterophyllum, Terminalia bellirica, Bauhinia variegata, Vanda roxburghii, and Cassia angustifolia were prepared by maceration method, and preliminary screening studies to check their antimitotic activity were done by V. radiata germination inhibition assay, followed by A.

Formulation, Solubilization, and In Vitro Characterization of Quercetin-Incorporated Mixed Micelles of PEO-PPO-PEO Block Copolymers.

Quercetin (QCN) is a plant polyphenol with a variety of medicinal effects. Poor water solubility, on the other hand, restricts its therapeutic effectiveness. The purpose of this study was to develop mixed micellar systems using two biocompatible amphiphilic PEO-PPO-PEO triblock copolymers, Pluronic P123 (EO-PO-EO) and Pluronic F88 (EO-PO-EO), in order to enhance the aqueous solubility and oral bioavailability of QCN drug.

DNA interaction, anticancer, cytotoxicity and genotoxicity studies with potential pyrazine-bipyrazole dinuclear µ-oxo bridged Au(III) complexes.

Pyrazine-bipyrazole-based µ-oxo bridged dinuclear Au(III) complexes were synthesized and characterized by various spectrometric (H-NMR, C (APT) NMR, FT-IR, Mass spectrometry) and analytical techniques (elemental analysis and conductance measurement). The evaluation of DNA binding activity by UV-Vis absorption spectra and viscosity measurement demonstrated that all the compounds intercalate in between the stacks of DNA base pair and the binding constant values were observed in the range of 5.4 × 10-2.

Synthesis, characterization, and biological applications of pyrazole moiety bearing osmium(IV) complexes.

Osmium (IV) complexes with pyrazole nucleus containing ligands were synthesized. Os(IV) compounds were characterized using ESI-MS, ICP-OES, IR spectroscopy, electronic spectroscopy, conductance, and magnetic measurements. Whereas, ligands were characterized by heteronuclear spectroscopy, (H and C), IR spectroscopy, and elemental analysis.

Upregulation of NOX-2 and Nrf-2 Promotes 5-Fluorouracil Resistance of Human Colon Carcinoma (HCT-116) Cells.

Altered expression of cellular redox genes and proteins contributes to invasion, metastasis, and drug resistance in cancer. NADPH oxidase (NOX) isoforms are the pro-oxidant enzymes that generate ROS as a primary product. Dysregulation of NOX activity and expression alters ROS generation, which either directly or indirectly modulates cell death and survival signaling during the progression of cancer.

Mechanistic insight of cell anti-proliferative activity of fluoroquinolone drug-based Cu(II) complexes.

Pefloxacin-based mixed ligand Cu(II) complexes with substituted isatin of type [Cu(Isatin)(Pefloxacin)Cl] were synthesized, and characterized by EPR, mass, FT-IR, electronic spectrometry, metal content, magnetic moment, and conductance measurement. The g factors g [Formula: see text] > g [Formula: see text] > 2.0023 observed in EPR suggest a square-pyramidal environment of ligands around the copper metal.

Synthesis, Characterization and Biological Application of Pyrazolo[1,5-a]pyrimidine Based Organometallic Re(I) Complexes.

The neutral rhenium(I) complexes (I-VI) of type [ReCl(CO)3Ln-] where L1 = 7-phenyl-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L2 = 7-(4-bromophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimi- dine, L3 = 7-(4-chlorophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L4 = 7-(2-chlorophenyl) -5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L5 = 7-(4-methoxyphenyl)-5-(pyridin-2-yl)pyrazolo [1,5-a]pyrimidine, L6 = 5-(pyridin-2-yl)-7-(p-tolyl)pyrazolo[1,5-a]pyrimidine were synthesized and characterized by 13C-APT, 1H-NMR, IR, electronic spectra, magnetic moment and conductance measurement. The anti-proliferative activity on HCT116 cells by MTT assay suggests potent cytotoxic nature of complexes, even some complexes have better activity than standard drug cisplatin, oxaliplatin, and carboplatin. The complexes found to have better antimicrobial activity compare to pyrazolo pyrimidine ligands.

Fluorescence, DNA Interaction and Cytotoxicity Studies of 4,5-Dihydro-1H-Pyrazol-1-Yl Moiety Based Os(IV) Compounds: Synthesis, Characterization and Biological Evaluation.

Osmium(IV) pyrazole compounds and ligands were synthesized and well characterised. Ligands were characterized by heteronuclear NMR spectroscopy (H & C), elemental analysis, IR spectroscopy and liquid crystal mass spectroscopy. Os(IV) complexes were characterized by ESI-MS, ICP-OES, IR spectroscopy, conductance measurements, magnetic measurements and electronic spectroscopy.

Nimbolide induces cell death in T lymphoma cells: Implication of altered apoptosis and glucose metabolism.

Nimbolide is a tetranortriterpenoid derived from the leaves and flowers of Azadirachta indica (Neem). It exhibits anticancer activity against a variety of cancers by modulating various crucial features, including cell proliferation, apoptosis, and invasion and metastasis. More importantly, the cytotoxic effect of nimbolide has also been observed against T cell lymphoma, but the underlying mechanisms are still unexplored.

Molecular and cellular paradigms of multidrug resistance in cancer.

Background: The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for the treatment of cancer. However, cancer cells reprogram themselves in multiple ways to evade the effect of these therapies, and over a period of time, the drug becomes inactive due to the development of multi-drug resistance (MDR).

AGE-RAGE synergy influences programmed cell death signaling to promote cancer.

Advanced glycation end products (AGEs) are formed as a result of non-enzymatic reaction between the free reducing sugars and proteins, lipids, or nucleic acids. AGEs are predominantly synthesized during chronic hyperglycemic conditions or aging. AGEs interact with their receptor RAGE and activate various sets of genes and proteins of the signal transduction pathway.

Molecular insights of NADPH oxidases and its pathological consequences.

Reactive oxygen species (ROS), formed by the partial reduction of oxygen, were for a long time considered to be a byproduct of cellular metabolism. Since, increase in cellular levels of ROS results in oxidative stress leading to damage of nucleic acids, proteins, and lipids resulting in numerous pathological conditions; ROS was considered a bane for aerobic species. Hence, the discovery of NADPH oxidases (NOX), an enzyme family that specifically generates ROS as its prime product came as a surprise to redox biologists.

Cell-Penetrable Peptide-Conjugated FADD Induces Apoptosis and Regulates Inflammatory Signaling in Cancer Cells.

Dysregulated expression of Fas-associated death domain (FADD) is associated with the impediment of various cellular pathways, including apoptosis and inflammation. The adequate cytosolic expression of FADD is critical to the regulation of cancer cell proliferation. Importantly, cancer cells devise mechanisms to suppress FADD expression and, in turn, escape from apoptosis signaling.

Biological activities of pyrazoline-indole based Re(I) carbonyls: DNA interaction, antibacterial, anticancer, ROS production, lipid peroxidation, in vivo and in vitro cytotoxicity studies.

Hetero mononuclear rhenium(I) metal complexes (I-V) using different substituted indole-pyrazoline based ligands were synthesized and characterized by spectroscopic and analytical methods. The binding of the rhenium complexes to Herring sperm DNA was monitored by UV spectroscopy, viscosity measurements, and molecular docking studies; groove binding was suggested as the most possible mode and the DNA-binding constants of the complexes were evaluated. In vivo and in vitro cytotoxicity of compounds were evaluated against the brine shrimp and S.

Surface modified PAMAM dendrimers with gallic acid inhibit, cell proliferation, cell migration and inflammatory response to augment apoptotic cell death in human colon carcinoma cells.

To overcome the obstacle of anti-cancer therapy significant attention has been drawn for improving drug delivery system. Since recent past, different approaches were applied using synthetic or natural derivatives for improving efficacy of anti-cancer drugs in cancer therapeutics. Gallic acid (GA) is a natural polyphenol, which exhibits a broad spectrum of biological activities, but its therapeutic application was limited due to poor bioavailability and toxicity.

Escherichia coli strain engineering for enhanced production of serratiopeptidase for therapeutic applications.

Serratiopeptidase is an extracellular zinc-containing metalloprotease that is produced by Serratia marcescens having molecular weight of about 53kD. It has shown therapeutic (anti-inflammatory, anti-fibrinolytic and analgesic) as well as industrial applications (detergents, food processing, leather, paper and brewing etc.).

Cell apoptosis induced by ciprofloxacin based Cu(II) complexes: cytotoxicity, SOD mimic and antibacterial studies.

The current cancer research focuses on the design and synthesis of chemical compounds that can modulate cell apoptosis or programmed cell death. So we synthesized and characterized ciprofloxacin based copper(II) complexes and studied their anticancer activity against HCT 116 cancer cells by MTT assay. We further investigated the influence of compound-2 (better IC value than cisplatin) on cancer cells to know the exact mechanism of anticancer activity.

Tetrazolo[1,5-a]quinoline moiety-based Os(IV) complexes: DNA binding/cleavage, bacteriostatic and photocytotoxicity assay.

Biological applications of platinum group metal-based complexes have been widely explored in synthetic and inorganic chemistry. The compounds have been subjected to DNA binding, DNA cleavage, and photocytotoxicity (HCT-116 cell line) and bacteriostatic activities. Binding constant of complexes are 1.

DNA interaction, in vivo and in vitro cytotoxicity, reactive oxygen species, lipid peroxidation of -N, S donor Re(I) metal complexes.

N, S donor ligands (L-L){L-L = 1,5-bis(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L), 1-(4-bromophenyl)-5-(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L), 5-(4-chlorophenyl)-3-(thiophen-2-yl)-1-(p-tolyl)-4,5-dihydro-1H-pyrazole (L), 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L), 5-(4-chlorophenyl)-1-(4-nitrophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L)} were synthesized by Claisen-Schmidt condensation and characterized by spectrometric methods. The complexes (I-V) were synthesized by ligand combination followed by metal chelation. The binding of the rhenium complexes to Herrin sperm DNA was monitored by UV spectroscopy and viscosity measurements.

Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibits pro-inflammatory cytokines in human breast adenocarcinoma cells.

Background: Curcumin is a natural derivative, which exhibits broad spectrum biological activities including anti-oxidant, anti-inflammatory, and anti-cancer. Since ancient times, it has been used for the treatment of various diseases. Many reports highlighted its potential as a chemopreventive and chemotherapeutic agent.