Anti-cancer drug-mediated increase in mitochondrial mass limits the application of metabolic viability-based MTT assay in cytotoxicity screening.

The high-throughput metabolic viability-based colorimetric MTT test is commonly employed to screen the cytotoxicity of different chemotherapeutic drugs. The assay assumes a cell density-dependent linear correlation with the MTT spectral absorbance. Therefore, the present study aimed to compare the cytotoxicity assessment between the MTT assay and gold standard cell number enumeration.

Granular Hemostatic Composite of Alginate, Calcium, and Zinc for Rapid and Effective Management of Post-Traumatic Hemorrhage.

Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made to develop hemostatic agents that can effectively reduce hemorrhage in the immediate aftermath of a traumatic event. The present study investigated the potential efficacy of Ca and Zn supplemented sodium alginate-based dry hemostatic particles (SA-CZ DHP) to manage excessive blood loss or post-traumatic hemorrhage.

Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a heterogeneous tumor with a poor prognosis and high metastatic potential, resulting in poor clinical outcomes, necessitating investigation to devise effective therapeutic strategies. Multiple studies have substantiated the anti-cancer properties of the naturally occurring flavonoid "Myricetin" in various malignancies. However, the therapeutic application of Myricetin is impeded by its poor water solubility and low oral bioavailability.

A calcium and zinc composite alginate hydrogel for pre-hospital hemostasis and wound care.

We developed, characterized, and examined the hemostatic potential of sodium alginate-based Ca and Zn composite hydrogel (SA-CZ). SA-CZ hydrogel showed substantial in-vitro efficacy, as observed by the significant reduction in coagulation time with better blood coagulation index (BCI) and no evident hemolysis in human blood. SA-CZ significantly reduced bleeding time (≈60 %) and mean blood loss (≈65 %) in the tail bleeding and liver incision in the mice hemorrhage model (p ≤ 0.

Mitochondrial uncoupler DNP induces coexistence of dual-state hyper-energy metabolism leading to tumor growth advantage in human glioma xenografts.

Introduction: Cancer bioenergetics is an essential hallmark of neoplastic transformation. Warburg postulated that mitochondrial OXPHOS is impaired in cancer cells, leading to aerobic glycolysis as the primary metabolic pathway. However, mitochondrial function is altered but not entirely compromised in most malignancies, and that mitochondrial uncoupling is known to increase the carcinogenic potential and modifies treatment response by altering metabolic reprogramming.

Protective Effect of Organ Preservation Fluid Supplemented With Nicorandil and Rutin Trihydrate: A Comparative Study in a Rat Model of Renal Ischemia.

Objectives: The objective of organ preservation is sustained viability of detached/removed/isolated organs and subsequent successful posttransplant outcomes. Nicorandil (an ATP-sensitive potassium channel opener) is an efficacious agent to preserve lungs and heart. Rutin trihydrate (an antioxidant) inhibits free radical-mediated cytotoxicity and lipid peroxidation.

Glycolytic inhibitor 2-deoxy-d-glucose attenuates SARS-CoV-2 multiplication in host cells and weakens the infective potential of progeny virions.

Aims: Virus-infected host cells switch their metabolism to a more glycolytic phenotype, required for new virion synthesis and packaging. Therefore, we investigated the effect and mechanistic action of glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) on virus multiplication in host cells following SARS-CoV-2 infection.

Main Methods: SARS-CoV-2 induced change in glycolysis was examined in Vero E6 cells.

Sphingosine kinase inhibitor, SKI-II confers protection against the ionizing radiation by maintaining redox homeostasis most likely through Nrf2 signaling.

Exposure to ionizing radiation (IR) set a series of deleterious events causing acute radiation syndrome and mortality, posing the need for a potent and safe radio-protective drug. IR induces cell death predominantly by causing oxidative stress and macromolecular damage. The pre-existing antioxidant defence machinery of the cellular system plays a crucial role in protecting the cells against oxidative stress by activation of Nrf2.

Mild mitochondrial uncoupling protects from ionizing radiation induced cell death by attenuating oxidative stress and mitochondrial damage.

Ionizing radiation (IR) induced mitochondrial dysfunction is associated with enhanced radiation stimulated metabolic oxidative stress that interacts randomly with intracellular bio-macromolecules causing lethal cellular injury and cell death. Since mild mitochondrial uncoupling emerged as a valuable therapeutic approach by regulating oxidative stress in most prevalent human diseases including ageing, ischemic reperfusion injury, and neurodegeneration with comparable features of IR inflicted mitochondrial damage. Therefore, we explored whether mitochondrial uncoupling could also protect from IR induced cytotoxic insult.

Non-Enzymatic Protein Acetylation by 7-Acetoxy-4-Methylcoumarin: Implications in Protein Biochemistry.

Background: The semi-synthetic acetoxycoumarins are known to acetylate proteins using novel enzymatic Calreticulin Transacetylase (CRTAase) system in cells. However, the nonenzymatic protein acetylation by polyphenolic acetates is not known.

Objective: To investigate the ability of 7-acetoxy-4-methyl coumarin (7-AMC) to acetylate proteins non-enzymatically in the test tube.

Hexokinase II inhibition by 3-bromopyruvate sensitizes myeloid leukemic cells K-562 to anti-leukemic drug, daunorubicin.

An increased metabolic flux towards Warburg phenotype promotes survival, proliferation and causes therapeutic resistance, in leukemic cells. Hexokinase-II (HK-II) is expressed predominantly in cancer cells, which promotes Warburg metabolic phenotype and protects the cancer cells from drug-induced apoptosis. The HK-II inhibitor 3- Bromopyruvate (3-BP) dissociates HK-II from mitochondrial complex, which leads to enhanced sensitization of leukemic cells to anti-leukemic drugs.

Mitochondrial biogenesis and metabolic hyperactivation limits the application of MTT assay in the estimation of radiation induced growth inhibition.

Metabolic viability based high throughput assays like MTT and MTS are widely used in assessing the cell viability. However, alteration in both mitochondrial content and metabolism can influence the metabolic viability of cells and radiation is a potential mitochondrial biogenesis inducer. Therefore, we tested if MTT assay is a true measure of radiation induced cell death in widely used cell lines.

Block Copolymer Based Nanoparticles for Theranostic Intervention of Cervical Cancer: Synthesis, Pharmacokinetics, and in Vitro/in Vivo Evaluation in HeLa Xenograft Models.

Polymer-based nanoparticles have proven to be viable carriers of therapeutic agents. In this study, we have developed nanoparticles (NPs) from polypeptide-polyethylene glycol based triblock and diblock copolymers. The synthesized block copolymers poly(ethylene glycol)-b-poly(glutamic acid)-b-poly(ethylene glycol) (GEG) and poly(ethylene glycol)-b-poly(glutamic acid) (EG) conjugated with folic acid for targeting specificity (EGFA) have been used to encapsulate methotrexate (MTX) to form M-GEG and M-EGFA NPs aimed at passive and active targeting of cervical carcinoma.

Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells.

Background: Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood.

Methods: We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz.