Semisynthesis of Alkaloid Derivatives: Pyranoacridone-Hydroxamic Acid Cytotoxic Conjugates with HDAC and Topoisomerase II α Dual Inhibitory Activity.

Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.

A Comprehensive Review on Preparation of Silver Nanoparticles from a Bacteriocin for the Natural Preservation of Food Products.

Food preservation aims to maintain safe and nutritious food for extended periods by inhibiting microbial growth that causes spoilage and poses health risks. Traditional chemical preservatives like sodium sulfite, sodium nitrite, sodium benzoate, tBHQ and BHA have raised concerns due to potential carcinogenicity, genotoxicity and allergies with long-term consumption. As a natural alternative, bacteriocins have emerged for food preservation.

Dysregulation of protein degradation and alteration of secretome in α-synuclein-exposed astrocytes: implications for dopaminergic neuronal dysfunction.

Background: A key factor in the propagation of α-synuclein pathology is the compromised protein quality control system. Variations in membrane association and astrocytic uptake between different α-synuclein forms suggest differences in exocytosis or membrane cleavage, potentially impacting the secretome's influence on dopaminergic neurons. We aimed to understand differences in protein degradation mechanisms of astrocytes for both wild-type (WT) and mutant forms of α-synuclein, specifically during periods of reduced degradation efficiency.

Barriers to Mental Health Support in Cyberbullying: A Thematic Analysis of What Mental Health Professionals and Cyber Experts Think.

Background: Cyberbullying can be a traumatic experience for adolescents. It can affect their psychosocial functioning, development, and mental well-being in the long term. Though mental health support is needed to help adolescents, parents, and schools, they do not seek appropriate support.

Gold-thiol-beaded albumin nanoparticles for chemo-combined pulsatile plasmonic laser therapy of Rheumatoid arthritis in rat model.

Rheumatoid arthritis (RA) is a chronic inflammatory immune disease that causes synovial membrane inflammation and destruction of articular cartilage. Traditionally, methotrexate is a first-line drug for RA treatment. However, its therapeutic benefits are insufficient.

Advances in mass spectrometry for metabolomics: Strategies, challenges, and innovations in disease biomarker discovery.

Mass spectrometry (MS) plays a crucial role in metabolomics, especially in the discovery of disease biomarkers. This review outlines strategies for identifying metabolites, emphasizing precise and detailed use of MS techniques. It explores various methods for quantification, discusses challenges encountered, and examines recent breakthroughs in biomarker discovery.

A sustainable RP-HPLC method for concurrent estimation of capecitabine and celecoxib in liposomal formulation: Greenness and whiteness appraisal.

Liposomes have been reported for combination therapy due to their ability to carry both hydrophilic and lipophilic drugs together. The current investigation aims to develop a novel, eco-friendly, and sustainable reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous quantification of capecitabine and celecoxib co-encapsulated in liposomes. The method reported herein uses a C column (4.

Obstructive sleep apnea risk among adults with type 2 diabetes mellitus in an urban primary care setting of Mangalore, India.

Background: Obstructive sleep apnea (OSA) is an under-evaluated and under-treated problem, particularly among individuals with type 2 diabetes mellitus (T2DM). Therefore, in this study, we aim to determine the risk of OSA among adults with T2DM residing in an urban area of Mangalore and to elucidate the determinants of OSA among the study participants.

Materials And Methods: A cross-sectional study was conducted for a period of 2 months among adult patients (≥ 18 years) with T2DM seeking health care at a primary care setting located in an urban area of Mangalore.

Implementation of RSM and ANN Optimization Approach for Natural Deep Eutectic Solvents-Based Extraction of Bioactive Compounds from Orange Peel.

The present investigation has focused on developing an eco-friendly method to extract bioactive compounds from orange peel using natural deep eutectic solvents (NADES). NADES-II composed of choline chloride (ChCl) and ethylene glycol (1:2) and 50% water shows the maximal extraction yield with higher antioxidant activity in terms of DPPH and ABTS scavenging activity with a high total phenolic content (TPC) and total flavonoid content (TFC). The microwave-assisted extraction (MAE) process was optimized using response surface methodology (RSM) and an artificial neural network (ANN).

On-demand Opto-Laser activatable nanoSilver ThermoGel for treatment of full-thickness diabetic wound in a mouse model.

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models.

Selective recovery of esterase from Trichoderma harzianum through adsorption: Insights on enzymatic catalysis, adsorption isotherms and kinetics.

In recent years, numerous attempts have been made to develop a low-cost adsorbent for selectively recovering industrially important products from fermentation broth or complex mixtures. The current study is a novel attempt to selectively adsorb esterase from Trichoderma harzianum using cheap adsorbents like bentonite (BT), activated charcoal (AC), silicon dioxide (SiO), and titanium dioxide (TiO). AC had the highest esterase adsorption of 97.

Navigating the future of health care with AI-driven digital therapeutics.

Digital therapeutics (DTx) is a recently conceived idea in health care that aims to cure ailments and modify patient behavior by employing a range of digital technologies. Notably, when traditional medication is not entirely efficacious, DTx offers an innovative avenue for treatments linked to dysfunctional behaviors and lifestyle management. DTx involves extremely adaptable therapeutic devices that empower greater patient engagement in treating illness, using algorithms to collect, transfer and analyze the patient's data.

Preliminary study on cytotoxicity of selegiline on different cancer cell lines: exploration of the induction of ROS-independent apoptosis in breast cancer cells.

The concept of drug repurposing is now widely utilized by biomedical scientists for drug discovery. An example of this is the use of selegiline (SEL), a monoamine oxidase inhibitor that was initially used for the management of depression but is now being considered for another purpose. This study compares the cytotoxic effects of SEL on different cancer cells.

Lipidic Nanosystem as State-of-the-Art Nanovehicle for Biomedical Applications.

Unlabelled: Lipids have tremendously transformed the biomedical field, especially in the last few decades. Nanosystems, especially Lipid nanocapsules (LNCs), have emerged as the most demanding nanovehicle systems for delivering drugs, genes, and other diagnostic agents. Unique attributes and characteristic features such as higher encapsulation efficiency, stealth effect, ability to solubilize a wide range of drugs, capability to inhibit P-gp efflux pumps, and higher stability play a vital role in engaging this nanosystem.

Breakthroughs in road mapping IL-35 mediated immunotherapy for type-1 and autoimmune diabetes mellitus.

IL-35 is a recently discovered protein made up of IL-12α and IL-27β chains. It is encoded by IL12A and EBI3 genes. Interest in researching IL-35 has significantly increased in recent years, as evidenced by numerous scientific publications.

α-Linolenic Acid Vesicles-Mediated Tau Internalization in Microglia.

In Alzheimer's disease, the synaptic loss is prominent due to the accumulation of Amyloid βeta (Aβ) protein in synapses, which affect neurotransmission, and thus ultimately causes neuronal loss. Tau, a microtubule-associated protein, is a vital protein of intracellular neurofibrillary tangles (NFTs) in AD. Along with the accumulation of aberrant proteins, glial cells, mainly astrocytes and microglia, play a major role in impairing neuronal network.

G-protein coupled receptors regulates Tauopathy in neurodegeneration.

In Alzheimer's disease, the microtubule-associated protein, Tau misfolds to form aggregates and filaments in the intra- and extracellular region of neuronal cells. Microglial cells are the resident brain macrophage cells involved in constant surveillance and activated by the extracellular deposits. Purinergic receptors are involved in the chemotactic migration of microglial cells towards the site of inflammation.

The crosstalk between extracellular matrix proteins and Tau.

Alzheimer's disease is progressive neurodegenerative disease characterize by the presence of extracellular accumulation of amyloid-β plaques and intracellular deposits of neurofibrillary tangles of Tau. Apart from axonal depositions pathological aggregated Tau protein is known to secrete into extracellular spaces and propagate through seeding mechanism. Microglia, the immune cells of the brain display modest ability to internalize the extracellular Tau and degrade it through endolysosomal pathway.

An Update on Current Trend in Sample Preparation Automation in Bioanalysis: strategies, Challenges and Future Direction.

Automation in sample preparation improves accuracy, productivity, and precision in bioanalysis. Moreover, it reduces resource consumption for repetitive procedures. Automated sample analysis allows uninterrupted handling of large volumes of biological samples originating from preclinical and clinical studies.

Infusion of active compound into sliced button mushrooms through vacuum impregnation to improve functionality: Comparing response surface methodology and artificial neural network.

The present study explores the infusion of active compounds (ascorbic acid and calcium lactate) into sliced button mushrooms (Agaricus bisporus) to increase the nutritional value and reduce the browning effect of sliced mushrooms using the vacuum impregnation (VI) technique. The aim was to functionalize the vacuum-infused sliced mushrooms and evaluate the physicochemical properties of button mushrooms for diversifying food use. The central composite design was implemented to determine the optimized condition for the process with four independent factors, that is, immersion time (IT) 30-90 min, solution temperature (ST) 35-55°C, solution concentration (SC) 4%-12%, and vacuum pressure (VP) 50-170 mbar.