Eco-friendly approaches to 1,3,4-oxadiazole derivatives: A comprehensive review of green synthetic strategies.

This review article offers an environmentally benign synthesis of 1,3,4-oxadiazole derivatives, with a focus on sustainable methodologies that have minimal impact on the environment. These derivatives, known for their diverse applications, have conventionally been associated with synthesis methods that utilize hazardous reagents and produce significant waste, thereby raising environmental concerns. The green synthesis of 1,3,4-oxadiazole derivatives employs renewable substrates, nontoxic catalysts, and mild reaction conditions, aiming to minimize the environmental impact. Innovative techniques such as catalyst-based, catalyst-free, electrochemical synthesis, green-solvent-mediated synthesis, grinding, microwave-mediated synthesis, and photosynthesis are implemented, providing benefits in terms of scalability, cost-effectiveness, and ease of purification. This review emphasizes the significance of sustainable methodologies in the synthesis of 1,3,4-oxadiazole and boots for continued exploration in this research domain.

A Review on the Development of Novel Heterocycles as α-Glucosidase Inhibitors for the Treatment of Type-2 Diabetes Mellitus.

One of the most effective therapeutic decencies in the treatment of Type 2 Diabetes Mellitus is the inhibition of α-glucosidase enzyme, which is present at the brush border of the intestine and plays an important role in carbohydrate digestion to form mono-, di-, and polysaccharides. Acarbose, Voglibose, Miglitol, and Erniglitate have been well-known α-glucosidase inhibitors in science since 1990. However, the long synthetic route and side effects of these inhibitors forced the researchers to move their focus to innovate simple and small heterocyclic scaffolds that work as excellent α-glucosidase inhibitors. Moreover, they are also effective against the postprandial hyperglycemic condition in Type 2 Diabetes Mellitus. In this aspect, this review summarizes recent progress in the discovery and development of heterocyclic molecules that have been appraised to show outstanding inhibition of α-glucosidase to yield positive effects against diabetes.

Emerging green synthetic routes for thiazole and its derivatives: Current perspectives.

This review article provides an overview of the green synthesis of thiazole derivatives, emphasizing sustainable and environmentally friendly methodologies. Thiazole derivatives possess significant value and find diverse applications across various fields. However, conventional synthesis methods often involve hazardous reagents and generate substantial waste, posing environmental concerns. The green synthesis of thiazole derivatives employs renewable starting materials, nontoxic catalysts, and mild reaction conditions to minimize environmental impact. Innovative techniques such as microwave irradiation, ultrasound synthesis, green solvents, a green catalyst-based approach, and mechanochemistry-mediated synthesis are employed, offering advantages in terms of scalability, cost-effectiveness, and purification simplicity. The resulting thiazole derivatives exhibit comparable or enhanced biological activities, showcasing the feasibility and practicality of green synthesis in drug discovery. This review paper underscores the importance of sustainable approaches in functional molecular synthesis and encourages further research in this domain.

Effects of Intra-Amniotic Administration of the Hydrolyzed Protein of Chia (Salvia hispanica L.) and Lacticaseibacillus paracasei on Intestinal Functionality, Morphology, and Bacterial Populations, In Vivo (Gallus gallus).

As a protein source, chia contains high concentrations of bioactive peptides. Probiotics support a healthy digestive tract and immune system. Our study evaluated the effects of the intra-amniotic administration of the hydrolyzed chia protein and the probiotic Lacticaseibacillus paracasei on intestinal bacterial populations, the intestinal barrier, the inflammatory response, and brush border membrane functionality in ovo (Gallus gallus). Fertile broiler (Gallus gallus) eggs (n = 9/group) were divided into 5 groups: (NI) non-injected; (H2O) 18 MΩ H2O; (CP) 10 mg/mL hydrolyzed chia protein; (CPP) 10 mg/mL hydrolyzed chia protein + 106 colony-forming unit (CFU) L. paracasei; (P) 106 CFU L. paracasei. The intra-amniotic administration was performed on day 17 of incubation. At hatching (day 21), the animals were euthanized, and the duodenum and cecum content were collected. The probiotic downregulated the gene expression of NF-κß, increased Lactobacillus and E. coli, and reduced Clostridium populations. The hydrolyzed chia protein downregulated the gene expression of TNF-α, increased OCLN, MUC2, and aminopeptidase, reduced Bifidobacterium, and increased Lactobacillus. The three experimental groups improved in terms of intestinal morphology. The current results suggest that the intra-amniotic administration of the hydrolyzed chia protein or a probiotic promoted positive changes in terms of the intestinal inflammation, barrier, and morphology, improving intestinal health.

A Review on Recent Development of Novel Heterocycles as Acetylcholinesterase Inhibitor for the Treatment of Alzheimer's Disease.

Alzheimer's Disease (AD), affecting a large population worldwide, is characterized by the old population's loss of memory and learning ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed to treat AD, including naturallyderived inhibitors, synthetic analogs, and hybrids. Acetylcholinesterase (AChE) has obtained a renewed interest as a therapeutic target in Alzheimer's disease (AD) due to increased neural cells' function by increasing the concentration of acetylcholine. In this review, we reported the recent development of novel heterocyclic compounds such as coumarin-benzotriazole hybrids, carbazole derivatives, tacrine conjugates, N-benzyl-piperidine-aryl-acyl hydrazones hybrid, spiropyrazoline derivatives, coumarin-dithiocarbamate hybrids, etc., as AChE inhibitors for the treatment of Alzheimer disease. All the bioactive compounds show an effect on different cells and interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE with a narrow range of IC50 values from 0.4 nm to 88.21 µm using Ellman's in vitro AChE assay method and show high BBB permeability in vitro. In addition, the in vitro fluorescence assay study using Amplex Red assay kits revealed that all the compounds could inhibit self-induced ß-amyloid (Aß) aggregation with the highest inhibition range from 31.4 to 82%. Furthermore, most of the compounds show a low toxicity profile during in vivo studies. The results suggest that all the compounds constitute promising leads for the AChE targeted approach for Alzheimer's disease.

Enabling In Vivo Optical Imaging of an Osmium Photosensitizer by Micellar Formulation.

Osmium (Os)-based photosensitizers (PSs) exhibit unique broad, red-shifted absorption, favoring PDT activity at greater tissue depths. We recently reported on a potent Os(II) PS, rac-[Os(phen)2(IP-4T)](Cl)2 (ML18J03) with submicromolar hypoxia activity. ML18J03 exhibits a low luminescence quantum yield of 9.8 × 10-5 in PBS, which limits its capacity for in vivo luminescence imaging. We recently showed that formulating ML18J03 into 10.2 nm DSPE-mPEG2000 micelles (Mic-ML18J03) increases its luminescence quantum yield by two orders of magnitude. Here, we demonstrate that Mic-ML18J03 exhibits 47-fold improved accumulative luminescence signals in orthotopic AT-84 head and neck tumors. We show, for the first time, that micellar formulation provides up to 11.7-fold tumor selectivity for ML18J03. Furthermore, Mic-ML18J03 does not experience the concentration-dependent quenching observed with unformulated ML18J03 in PBS, and formulation reduces spectral shifting of the emission maxima during PDT (variance = 6.5 and 27.3, respectively). The Mic-ML18J03 formulation also increases the production of reactive molecular species 2-3-fold. These findings demonstrate that micellar formulation is a versatile and effective approach to enable in vivo luminescence imaging options for an otherwise quenched, yet promising, PS.

A Care Step Pathway for the Diagnosis and Treatment of COVID-19-Associated Invasive Fungal Infections in the Intensive Care Unit.

BACKGROUND: In March 2020, the World Health Organization declared COVID-19, caused by the SARS-CoV-2 virus, a pandemic. Patients with severe cases resulting in hospitalization and mechanical ventilation are at risk for COVID-19-associated pulmonary aspergillosis, an invasive fungal infection, and should be screened for aspergillosis if they have persistent hemodynamic instability and fever. Early detection and treatment of this fungal infection can significantly reduce morbidity and mortality in this population. OBJECTIVE: To develop an evidence-based care step pathway tool to help intensive care unit clinicians assess, diagnose, and treat COVID-19-associated pulmonary aspergillosis. METHODS: A panel of 18 infectious disease experts, advanced practice registered nurses, pharmacists, and clinical researchers convened in a series of meetings to develop the Care Step Pathway tool, which was modeled on a tool developed by advanced practice nurses to evaluate and manage side effects of therapies for melanoma. The Care Step Pathway tool addresses various aspects of disease management, including assessment, screening, diagnosis, antifungal treatment, pharmacological considerations, and exclusion of other invasive fungal coinfections. RESULTS: The Care Step Pathway tool was applied in the care of a patient with COVID-19-associated aspergillosis. The patient was successfully treated. CONCLUSION: The Care Step Pathway is an effective educational tool to help intensive care unit clinicians consider fungal infection when caring for COVID-19 patients receiving mechanical ventilation in the intensive care unit, especially when the clinical course is deteriorating and antibiotics are ineffective.

In silico Study and Solvent-free one-pot Synthesis of Tetrahydropyrimidine derivatives by Mechanochemistry Approach for Targeting Human Neutrophil Elastase against Lung Cancer.

BACKGROUND: Pyrimidine derivative has evinced its biological importance in targeting lung cancer by inhibiting neutrophil elastase. METHODS: All THPM derivatives were synthesized by the grindstone method at ambient temperature followed by molecular docking study for efficient binding interaction of THPM compounds by targeting human neutrophil elastase (HNE) (PDB ID: 5A0A) and In-silico ADMET study using PkCSM. Moreover, all synthesized compounds were characterized by spectroscopy techniques and screened for anti-cancer activity using in vitro HNE assay kit. RESULTS: We reported a one-pot solvent-free mechanochemical approach for synthesizing tetrahydropyrimidine (THPM) derivatives from various aromatic aldehydes, ethyl cyanoacetate, and urea followed by in silico study and evaluation against human neutrophil elastase (HNE) for treatment of lung cancer. We calibrated the best molecules that bound to specific targets more efficiently using a molecular docking approach and provided the desired efficacy. In-silico ADMET studies revealed that all best-scored compounds had drug-like characteristics for potential use as human neutrophil elastase inhibitors (HNE) in lung cancer treatment. Additionally, the in vitro studies revealed that compounds 1, 2, and 8 show potent HNE inhibitory activity for lung cancer treatment. CONCLUSION: In a nutshell, the tetrahydropyrimidine (THPM) scaffold and its derivatives may serve as potential HNE inhibitors for the development of a promising anti-cancer agent.

Analysis of change in knowledge, attitude, and practices about COVID-19 following and awareness session in rural population of Western India.

BACKGROUND: Beginning of the pandemic showed our limitations in our understanding of the spread of the dreaded coronavirus-19 that had sprung from China and spread through thick and thin across the world. The measures to contain the spread of virus in the absence of specific treatment protocol had everyone grope for the solutions in a very short time frame. One such is the knowledge, attitude, and practice in the rural setup. AIM: The aim of the study is to measure the change in knowledge, attitude, and practices (KAP) regarding COVID-19 following an awareness session in rural population. MATERIALS AND METHODS: A cross-section interventional study was carried out in January 2021. An interactive awareness session was conducted with the help of audiovisual aids following MOHFW guidelines for COVID-19, and the change in KAP about COVID-19 was measured by pre- and posttest standardized questionnaire. RESULTS: Of all the participants, statistically significant change in knowledge was seen from 43% to 52%. The villagers were educated about preventive steps and a positive change was measured in the practice of changing masks regularly (84%-100%), maintaining social distancing (44%-64%), frequent handwashing (52%-64%). No change was seen in wearing of masks (92%) and negative change was seen in avoiding handshakes (32%-28%). The preventive practices regarding COVID-19 pandemic changed significantly from 50% to 58%. Our study measured positive attitude change toward getting vaccinated from 64% to 72%. CONCLUSION: A single, short awareness session led to significant change in KAP about COVID-19 in rural population.

The immediate effects of soft tissue mobilization with proprioceptive neuromuscular facilitation on glenohumeral external rotation and overhead reach.

STUDY DESIGN: Randomized controlled 2-group. pretest-posttest, multivariate study of patients with shoulder musculoskeletal disorders. OBJECTIVES: The purpose of this study was to evaluate the immediate effect of soft tissue mobilization (STM) with proprioceptive neuromuscular facilitation (PNF) to increase glenohumeral external rotation at 45 degrees of shoulder abduction and overhead reach. BACKGROUND: It is postulated that limitation in glenohumeral external rotation, when measured at 45 degrees of shoulder abduction, represents subscapularis muscle flexibility deficits and is associated with the inability to fully reach overhead. No research, however, is available to demonstrate whether intervention strategies intended to improve subscapularis flexibility and glenohumeral external rotation range of motion at 45 degrees of shoulder abduction will improve a patient's ability to reach overhead. METHODS AND MEASURES: Twenty patients (10 males, 10 females; age range, 21-83 years) with limited glenohumeral external rotation and overhead reach of 1 year duration or less served as subjects. The subjects were randomly assigned to a treatment group, which consisted of soft tissue mobilization to the subscapularis and proprioceptive neuromuscular facilitation to the shoulder rotators, or a control group. Goniometric measurements of glenohumeral external rotation at 45 degrees abduction and overhead reach were taken preintervention and immediately postintervention for the treatment group or at prerest and postrest periods for the control group. RESULTS: The treatment group improved by a mean of 16.4 degrees (95% confidence interval [CI, 12.5 degrees-20.3 degrees) of glenohumeral external rotation, as compared to less than a 1 degree gain (95% CI, -0.2 degrees-2.0 degrees) in the control group (P < .0005). Overhead reach in the treatment group improved by a mean of 9.6 cm (95% CI, 5.2-14.0 cm) in comparison to a mean gain of 2.4 cm (95% CI, -0.8-5.6 cm) for the control group (P = .009). CONCLUSION: These findings suggest that a single intervention session of STM and PNF was effective for producing immediate improvements in glenohumeral external rotation and overhead reach in patients with shoulder disorders.