The Role of GLP-1, GIP, MCP-1 and IGFBP-7 Biomarkers in the Development of Metabolic Disorders: A Review and Predictive Analysis in the Context of Diabetes and Obesity.

Metabolic illnesses, including obesity and type 2 diabetes, have become worldwide epidemics that have an effect on public health. Clinical investigations and further exploration of these mechanisms could lead to innovative, effective, and personalized treatment strategies for individuals. It is important to screen biomarkers in previous studies to discover what is missing. Glucagon-like peptide-1's role in insulin secretion and glucose control highlights its diagnostic and therapeutic potential. Glucose-dependent insulinotropic peptide's influence on postprandial satiety and weight management signifies its importance in understanding metabolic processes. Monocyte chemoattractant protein-1's involvement in inflammation and insulin resistance underlines its value as a diagnostic marker. Insulin-like growth factor-binding protein-7's association with insulin sensitivity and kidney function presents it as a potential target for these diseases' management. In validating these biomarkers, it will be easier to reflect pathophysiological processes, and clinicians will be able to better assess disease severity, monitor disease progression, and tailor treatment strategies. The purpose of the study was to elucidate the significance of identifying novel biomarkers for type 2 diabetes mellitus and obesity, which can revolutionize early detection, risk assessment, and personalized treatment strategies. Standard literature searches of PubMed (MEDLINE), EMBASE, and Cochrane Library were conducted in the year 2023 to identify both original RCTs and recent systematic reviews that have explored the importance of identifying novel biomarkers for T2D and obesity. This search produced 1964 results, and then was reduced to randomized controlled trial and systematic reviews, producing 145 results and 44 results, respectively. Researchers have discovered potential associations between type 2 diabetes mellitus and obesity and the biomarkers glucagon-like peptide-1, glucose-dependent insulinotropic peptide, monocyte chemoattractant protein-1, and insulin-like growth factor-binding protein-7. Understanding the role of those biomarkers in disease pathogenesis offers hope for improving diagnostics, personalized treatment, and prevention strategies.

Nutritional Implications of Bariatric Surgery on Pregnancy Management-A Narrative Review of the Literature.

One in three women of reproductive age is obese. The mainstay treatment for obesity is bariatric surgery, and the following weight reduction results in a decrease in pregnancy adverse effects, including gestational diabetes mellitus, pregnancy-induced hypertension, and macrosomia. However, nutritional and vitamin deficiencies due to changes in the gastrointestinal tract after bariatric surgery are associated with an increase in the risk of fetal growth retardation and small for gestational-age neonates. The purpose of this review was to analyze the available recent literature on the subject of the management of pregnancy after bariatric surgery. We searched for available articles from 2007 to 2023 and chose articles of the greatest scientific and clinical value. Micronutrient, vitamin, and protein supplementation is recommended in the prenatal period and throughout the pregnancy. It is advised that pregnant women with a history of bariatric surgery should be provided with regular specialist dietary care. There is still a lack of recommendations about the optimum gestational weight gain after different types of bariatric surgery and for patients of different metabolic statuses. Women of reproductive age undergoing bariatric procedures should be provided with appropriate counseling about adequate contraception, the recommended time-to-conception interval, and the positive and negative influence of bariatric surgery on perinatal outcomes.

Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses.

The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.

Identification of Cellular Factors Required for SARS-CoV-2 Replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the recently emerged virus responsible for the COVID-19 pandemic. Clinical presentation can range from asymptomatic disease and mild respiratory tract infection to severe disease with lung injury, multiorgan failure, and death. SARS-CoV-2 is the third animal coronavirus to emerge in humans in the 21st century, and coronaviruses appear to possess a unique ability to cross borders between species and infect a wide range of organisms. This is somewhat surprising as, except for the requirement of host cell receptors, cell-pathogen interactions are usually species-specific. Insights into these host-virus interactions will provide a deeper understanding of the process of SARS-CoV-2 infection and provide a means for the design and development of antiviral agents. In this study, we describe a complex analysis of SARS-CoV-2 infection using a genome-wide CRISPR-Cas9 knock-out system in HeLa cells overexpressing entry receptor angiotensin-converting enzyme 2 (ACE2). This platform allows for the identification of factors required for viral replication. This study was designed to include a high number of replicates (48 replicates; 16 biological repeats with 3 technical replicates each) to prevent data instability, remove sources of bias, and allow multifactorial bioinformatic analyses in order to study the resulting interaction network. The results obtained provide an interesting insight into the replication mechanisms of SARS-CoV-2.

SARS-CoV-2 inhibition using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray.

There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19. Here we show that N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ), a positively charged polymer that has been through an extensive Good Laboratory Practice toxicology screen, is able to reduce the infectivity of SARS-COV-2 in A549ACE2+ and Vero E6 cells with a log removal value of - 3 to - 4 at a concentration of 10-100 µg/ mL (p < 0.05 compared to untreated controls) and to limit infectivity in human airway epithelial cells at a concentration of 500 µg/ mL (p < 0.05 compared to untreated controls). In vivo studies using transgenic mice expressing the ACE-2 receptor, dosed nasally with SARS-COV-2 (426,000 TCID50/mL) showed a trend for nasal GCPQ (20 mg/kg) to inhibit viral load in the respiratory tract and brain, although the study was not powered to detect statistical significance. GCPQ's electrostatic binding to the virus, preventing viral entry into the host cells, is the most likely mechanism of viral inhibition. Radiolabelled GCPQ studies in mice show that at a dose of 10 mg/kg, GCPQ has a long residence time in mouse nares, with 13.1% of the injected dose identified from SPECT/CT in the nares, 24 h after nasal dosing. With a no observed adverse effect level of 18 mg/kg in rats, following a 28-day repeat dose study, clinical testing of this polymer, as a COVID-19 prophylactic is warranted.