LC-ESI-HRMS-Based Evaluation of Antioxidants as Additives to Inhibit Genotoxic Nitrosamine Formation in Metformin Hydrochloride Tablets.

Nitrosamines, particularly N-nitrosodimethylamine (NDMA), have raised significant regulatory and safety concerns due to it's genotoxic and carcinogenic properties. Although NDMA formation in metformin hydrochloride (MET) tablets under nitrosating conditions is well-established, the potential of antioxidants to inhibit this impurity remains underexplored. This study evaluated the effectiveness of antioxidant additives, trolox (TRX), ascorbic acid (ASA), and alpha-tocopherol (Alpha- T), in minimizing NDMA formation during storage.

Mechanically induced development and maturation of 3D organoid platform: an organotypic heterogeneous microphysiological model of patient-derived organoids with ER/PR/HER2 breast cancer.

Introduction: Breast cancer comprises diverse histological and molecular subtypes, each characterized by distinct biological behaviors and therapeutic responses. So, to unravel the biological complexity of cancer tissue, we must research it down to the heterogeneous cell level, where one can investigate and deconstruct the molecular and biochemical characteristics of various cell types (Fibroblast, Endothelial Cells, and Cancer Stem cells). Unfortunately, advancements have been hindered due to the absence of thorough methods for identifying, isolating, and cultivating all patient-derived organoids (PDOs) types from various tissues.

Dehydrozingerone Improves Mood and Memory in Diabetic Mice via Modulating Core Neuroimmune Genes and Their Associated Proteins.

Patients with poorly managed diabetes are at a greater risk of developing dementia and experiencing accelerated brain aging due to elevated blood glucose levels. Furthermore, patients with diabetes frequently encounter challenges with memory, recall, and concentration while carrying out their daily activities. The goal of this study was to investigate whether dehydrozingerone, a structural half-analog of curcumin, might improve mood and cognition in diabetics using a well-established mouse model of type 2 diabetes (T2DM) induced by a high-fat diet (HFD) and low streptozotocin (STZ) doses.

Progression of tuberculosis among patients with rheumatic diseases - A systematic review and meta-analysis.

Background: Tuberculosis is a contagious disease that ranks among the top ten killers of humans worldwide. Mycobacterium tuberculosis is an etiological agent of tuberculosis. The prognosis of tuberculosis in patients with autoimmune diseases is high due to treatment with anti-TNF-alpha therapy.

7-Hydroxyflavone Mitigates Osteoporosis Via Key Signaling Pathways in a Dexamethasone-induced Rat Model.

Background: Osteoporosis is a deteriorating skeletal bone disorder that affects in a silent, asymptomatic way. On-demand for new therapeutic strategies, natural products have gained attention as a significant alternative for treating osteoporosis. 7-Hydroxyflavone (7HF) is one of the well-known natural flavones for its anti-inflammatory, anti-oxidant, anti-diabetic, and neuroprotective, which was investigated at the molecular level for restoring bone homeostasis against dexamethasone-induced osteoporosis in vivo with a focus on modulation of oxidative stress (caspase- 3), GATA-3, and NF-kB signaling along with in silico ADMET analysis.

Dehydrozingerone ameliorates renal structure compromised in diabetic nephropathy.

Kidney structural integrity is critical for bodily excretory mechanism. Diabetes has been considered as one of the major risk factors for chronic kidney disease, but the underlying mechanism remains elusive. The present study investigates the transcriptomic and proteomic profiling of long-term impact of high-fat diet (HFD) on renal tissue in mice and role of dehydrozingerone (DH) in reinstating the normal kidney function.

Role of Microneedles for Improved Treatment of Obesity: Progress and Challenges.

Obesity is a global metabolic health epidemic characterized by excessive lipid and fat accumulation, leading to severe conditions such as diabetes, cancer, and cardiovascular disease. Immediate attention and management of obesity-related health risks are most warranted. The imbalance between fat absorption, metabolic rate, and environmental and genetic factors is responsible for obesity.

Fabrication of multilayer heterogeneous cell assembly for pathophysiologically relevant 3DIBD disease model for high throughput drug screening.

Regarding the approval of novel pharmaceuticals, the most common reason for failure is inadequate oral drug bioavailability. Owing to the complex physiological milieu of the human intestine, which is characterized by its varied composition, various functions, and one-of-a-kind dynamic conditions, it is difficult to reproduce the organ. Traditional monolayers in two dimensions, sophisticated three-dimensional systems, and developing fluid-dynamic platforms are examples ofintestinal models.

Impact of microwave-assisted acid extraction (MW-AAE) methods on simultaneous ICP-MS analysis of multi-elements in edibles besides associated greenness and human health risk assessment.

In this study, a total of 13 hazardous multi-elements have been simultaneously determined in 24 edibles using inductively coupled plasma-mass spectrometry (ICP-MS). As per the ICHQ3D document, the detected elements belong to Class 1 (As, Cd, and Pb), Class 2A (Co, V, and Ni), Class 2B (TI, Pd, Se, and Ag), and Class 3 (Ba, Cu, and Cr). The impact of various microwave-assisted acid extraction (MW-AAE) methods (A, B, and C) on multielement from edibles and sensitivity detection was comparatively studied.

Aerobic exercise and metformin attenuate the cognitive impairment in an experimental model of type 2 diabetes mellitus: focus on neuroinflammation and adult hippocampal neurogenesis.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that increases the prevalence of cognitive impairment in the geriatric population. Aerobic exercise is an excellent non-pharmacological therapeutic strategy to prevent Alzheimer's disease, the most common form of dementia. The exact molecular mechanism of aerobic exercise (Exe) as an intervention to counter cognitive decline is far from clear.

Computational and biochemical characterization of the immobilized esterase of Salinicoccus roseus for pesticide degradation.

The continuous exposure of chemical pesticides in agriculture, their contamination in soil and water pose serious threat to the environment. Current study used an approach to evaluate various pesticides like Hexaconazole, Mancozeb, Pretilachlor, Organophosphate and λ-cyhalothrin degradation capability of esterase. The enzyme was isolated from Salinicoccus roseus.

Development of bioengineered 3D patient derived breast cancer organoid model focusing dynamic fibroblast-stem cell reciprocity.

Three-dimensional (3D) models, such as tumor spheroids and organoids, are increasingly developed by integrating tissue engineering, regenerative medicine, and personalized therapy strategies. These advanced 3Dmodels are not merely endpoint-driven but also offer the flexibility to be customized or modulated according to specific disease parameters. Unlike traditional 2D monolayer cultures, which inadequately capture the complexities of solid tumors, 3D co-culture systems provide a more accurate representation of the tumor microenvironment.

Exploring diabesity pathophysiology through proteomic analysis using .

Introduction: Diabesity, characterized by obesity-driven Type 2 diabetes mellitus (T2DM), arises from intricate genetic and environmental interplays that induce various metabolic disorders. The systemic lipid and glucose homeostasis is controlled by an intricate cross-talk of internal glucose/insulin and fatty acid molecules to maintain a steady state of internal environment.

Methods: In this study, were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients to delve into the mechanistic foundations of diabesity.

Leveraging solid solubility and miscibility of etoricoxib in Soluplus® towards manufacturing of 3D printed etoricoxib tablets by additive manufacturing.

This research focuses on exploring the solid solubility and miscibility of Etoricoxib, a poorly water-soluble anti-inflammatory drug, within Soluplus®, a polymer used as a matrix for 3D-printed tablets. By utilizing hot-melt extrusion (HME), the drug was dispersed within Soluplus® to enhance its solubility. The extrudates were then employed in 3D printing to create customized solid oral dosage form.

The onset and the development of cardiometabolic aging: an insight into the underlying mechanisms.

Metabolic compromise is crucial in aggravating age-associated chronic inflammation, oxidative stress, mitochondrial damage, increased LDL and triglycerides, and elevated blood pressure. Excessive adiposity, hyperglycemia, and insulin resistance due to aging are associated with elevated levels of damaging free radicals, inducing a proinflammatory state and hampering immune cell activity, leading to a malfunctioning cardiometabolic condition. The age-associated oxidative load and redox imbalance are contributing factors for cardiometabolic morbidities via vascular remodelling and endothelial damage.

Rebamipide nanocrystal with improved physicomechanical properties and its assessment through bio-mimicking 3D intestinal permeability model.

This study investigated the formulation and characterization of rebamipide nanocrystals (REB-NCs) to enhance the solubility and permeability of rebamipide, an anti-ulcer medication known for its low aqueous solubility and permeability, classified as BCS class IV. Employing high-pressure homogenization and wet milling techniques, we successfully achieved nanonization of rebamipide, resulting in stable nanosuspensions that were subsequently freeze-dried to produce REB-NCs with an average particle size of 223 nm. Comprehensive characterization techniques, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) confirmed the crystalline nature of the nanocrystals and their compatibility with the selected excipients.

Current Strategies for Combating Biofilm-Forming Pathogens in Clinical Healthcare-Associated Infections.

The biofilm formation by various pathogens causes chronic infections and poses severe threats to industry, healthcare, and society. They can form biofilm on surfaces of medical implants, heart valves, pacemakers, contact lenses, vascular grafts, urinary catheters, dialysis catheters, etc. These biofilms play a central role in bacterial persistence and antibiotic tolerance.

Dehydrozingerone ameliorates arsenic-induced reproductive toxicity in male Wistar rats.

Arsenic (As), a significant environmental pollutant that has garnered global attention, is widely recognized for its adverse effects on reproductive health. This study assesses the aphrodisiac activity of Dehydrozingerone (DHZ) against As induced sexual dysfunction in male Wistar rats. Male Wistar rats were divided into control, As, and As+DHZ groups.

Decellularized extracellular matrix-based bioengineered 3D breast cancer scaffolds for personalized therapy and drug screening.

Breast cancer (BC) is the second deadliest cancer after lung cancer. Similar to all cancers, it is also driven by a 3D microenvironment. The extracellular matrix (ECM) is an essential component of the 3D tumor micro-environment, wherein it functions as a scaffold for cells and provides metabolic support.

Naringin and temozolomide combination suppressed the growth of glioblastoma cells by promoting cell apoptosis: network pharmacology, assays and metabolomics based study.

Glioblastoma, which affects a large number of patients every year and has an average overall lifespan of around 14.6 months following diagnosis stands out as the most lethal primary invasive brain tumor. Currently, surgery, radiation, and chemotherapy with temozolomide (TMZ) are the three major clinical treatment approaches.

A mechanistic study on the tolerance of PAM distal end mismatch by SpCas9.

The therapeutic application of CRISPR-Cas9 is limited due to its off-target activity. To have a better understanding of this off-target effect, we focused on its mismatch-prone PAM distal end. The off-target activity of SpCas9 depends directly on the nature of mismatches, which in turn results in deviation of the active site of SpCas9 due to structural instability in the RNA-DNA duplex strand.

ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy.