Insight into the Predictive Power of Surrogate Diagnostic Indices for Identifying Individuals with Metabolic Syndrome.

BACKGROUND: This study aimed to assess the diagnostic capability of insulin surrogate measurements in identifying individuals with metabolic syndrome (MetS) and propose applicable indices derived from fasting values, particularly in large study populations. METHODS: Data were collected from the datasets of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS). MetS was defined based on the National Cholesterol Education Program (NCEP) criteria. Various insulin surrogate indices, including Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), Fasting glucose to insulin ratio (FGIR), Reynaud, Reciprocal insulin, McAuley, Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-glucose index (TyG), TG/ HDL-C, TG/ BMI, and TG/ WC ratio were assessed. Receiver Operating Characteristic (ROC) curves were used to assess pathologic conditions and determine the optimal cut-off through the highest score of the Youden index. Also, Area Under the Curve (AUC) values were established for each index totally and according to sex, age, and BMI differences. RESULTS: The study population consisted of 373 individuals (49.9% women; 75.1% middle age, 39.1% obese, and 27.3% overweight), of whom 117 (31.4%) had MetS. The METS-IR (AUC: 0.856; 95% CI: 0.817-0.895), TG/ HDL-C (AUC: 0.820; 95% CI: 0.775-0.886), TyG (AUC: 0.808; 95% CI: 0.759-0.857), and McAuley (AUC: 0.804; 95% CI: 0.757-0.852) indices provided the greatest AUC respectively for detection of MetS. The values of AUC for all the indices were higher in men than women. This trend was consistent after data stratification based on BMI categories, middle age, and senile individuals. CONCLUSION: The present study indicated that indices of insulin, including METS-IR, TG/HDLC, TyG, and McAuley, have an equal or better capacity in determining the risk of MetS than HOMA-IR, are capable of identifying individuals with MetS and may provide a simple approach for identifying populations at risk of insulin resistance.

Extracellular vesicles biogenesis, isolation, manipulation and genetic engineering for potential in vitro and in vivo therapeutics: An overview.

The main goals of medicine consist of early detection and effective treatment of different diseases. In this regard, the rise of exosomes as carriers of natural biomarkers has recently attracted a lot of attention and managed to shed more light on the future of early disease diagnosis methods. Here, exosome biogenesis, its role as a biomarker in metabolic disorders, and recent advances in state-of-art technologies for exosome detection and isolation will be reviewed along with future research directions and challenges regarding the manipulation and genetic engineering of exosomes for potential in vitro and in vivo disease diagnosis approaches.

Appraisal of SARS-CoV-2 mutations and their impact on vaccination efficacy: an overview.

With the unexpected emergence of the novel 2019 Wuhan coronavirus, the world was faced with a sudden uproar that quickly shifted into a serious life-threatening pandemic. Affecting the lives of the global population and leaving drastic damage in various sections and systems, several measures have been constantly taken to tackle down this crisis. For instance, numerous vaccines have been developed in the past two years, some of which have been granted emergency use, thus providing sufficient immunity to the vaccinated individuals. However, the appearance of newly emerged SARS-CoV-2 variants with accelerated transmission and fatality has led the world towards another pandemic. Having undergone various mutations in genomic and/or amino acid profiles, some of the emerged variants of concern (VOCs) including Alpha, Beta, Gamma, and Delta have displayed immune evasion and pathogenicity even in the vaccinated population, hence raising concerns regarding the efficacy of current vaccines against new VOCs of COVID-19. Therefore, genomic investigations of SARS-CoV-2 mutations are expected to provide valuable insight into the evolution of SARS-CoV-2, while also determining the impact of different mutations on infection severity. This study was constructed with the aim of shining light on recent advances regarding mutations in major COVID-19 VOCs, as well as vaccination efficacy against those VOCs.

Magnetic casein aggregates as an innovative support platform for laccase immobilization and bioremoval of crystal violet.

In this study, casein@CoFe2O4 was fabricated through a green synthesis methodology and applied to immobilize laccase. The constructed casein@CoFe2O4 exhibited porous structures with distinct cavities and suitable magnetic properties. The abundance of aromatic functional groups on the surface renneted casein and possible π-type interaction between laccase and para-κ-casein resulted in a successful immobilization. The biocatalyst retained 50% of its initial activity after 24 reusability cycles, indicating stable immobilization of laccase onto the casein microstructures. The stability of laccase after immobilization was improved by 300% in comparison with the free enzyme, especially in basic pH values. The constructed laccase@casein@CoFe2O4 was then incorporated to remove crystal violet (CV) as an environmentally harmful synthetic tri-phenylmethane dye. The prepared heterogeneous biocatalyst effectively diminished the antimicrobial activity of CV up to 81.3% in 40 min against some bacterial strains, resulting from the formation of more minor toxic metabolites identified by liquid chromatography coupled with mass spectroscopy after degradation procedure. The proposed green and feasible method for the preparation of magnetic casein aggregates has not been previously reported. The incorporation of casein, which acted as a molecular chaperon, resulted in a significant improvement in the enzymatic stability and exhibited appropriate reusability for the constructed biocatalytic system.

Developing a professional guideline for the use of cyberspace by health-care professionals in Iran: a mixed methods study.

The present study aimed to compile and develop a professional guideline for health-care providers in Iran regarding cyberspace usage. This was a mixed-methods study, conducted in three phases. In the first phase, the principles of ethics in cyberspace were collected through a review of the literature and available documents, and were then subjected to content analysis. In the second phase, the views of experts on medical ethics, virtual education, information technology and medical education, as well as clinical sciences experts and representatives of medical students and graduates were evaluated using the focus group method. In the third phase, the draft was evaluated by various stakeholders. Finally, after receiving the comments, the necessary modifications were applied to the guideline. The professional guideline for the use of cyberspace by health-care professionals comprised 30 codes in 5 domains, including the general regulations domain, care and treatment, research, education, and personal development. This guideline presents the various ways professionalism can be maintained in cyberspace interactions. Adherence to the principles of professionalism in cyberspace is required to protect and preserve the public trust in health-care professionals.

Depinar, a drug that potentially inhibits the binding and entry of COVID-19 into host cells based on computer-aided studies.

BACKGROUND AND PURPOSE: The new coronavirus (Covid-19) has resulted in great global concerns. Due to the mortality of this virus, scientists from all over the world have been trying to employ different strategies to tackle down this concern. This virus enters cells via phagocytosis through binding to the angiotensin-converting enzyme II receptor. After invading the body, it can stay hidden in there for a period of up to 24 days (incubation period). EXPERIMENTAL APPROACH: In this report, by the use of in silico studies we selected several FDA-approved compounds that possess antiviral properties. We chose the viral Spike protein as the target of drug compounds and carried out the screening process for the FDA databank in order to find the most effective ligand. FINDINGS/RESULTS: The results from dock and MD revealed 10 compounds with high affinity to the receptor-binding domain motif of S protein. The best inhibitors were the ingredients of Depinar, which managed to effectively block the interactions between cells and virus. CONCLUSION AND IMPLICATION: The results of this study were approved by in silico studies and due to the lack of time; we did not test the efficiency of these compounds through in vitro and in vivo studies. However, the selected compounds are all FDA approved and some are supplements like vitamin B12 and don't cause any side effects for patients.

Drug discovery strategies for modulating oxidative stress in gastrointestinal disorders.

INTRODUCTION: Due to the ever-growing incidence of gastrointestinal disorders accompanied by substantial economic impact, it is of great importance to manage these conditions globally. Since the significant role of oxidative stress has been proved in the initiation and propagation of most of the gastrointestinal disorders, medical science is now moving toward fusing traditional knowledge with advanced technology, aiming to promote the use of antioxidants in gastrointestinal disorders. AREAS COVERED: Through PubMed, the Cochrane library, the WHO, Clinicaltrials.gov and Google Scholar, the US FDA, and EMA, the authors collated and reviewed the appropriate literature published between the 1 January 2015 and 31 March 2020 and provided their expert perspectives on the drug discovery strategies for modulating oxidative stress in gastrointestinal disorders. EXPERT OPINION: As with other pharmaceuticals, antioxidants have been generally developed following the basic principles of drug discovery; the recent focus of which is designing multi-potent natural antioxidants mainly through using rational design and target-based drug discovery strategies. Although there have been encouraging in-vivo studies on the use of antioxidants in gastrointestinal disorders, especially inflammatory bowel disease and gastritis, there have been considerable deficits regarding in-vitro and clinical applications that should be immediately addressed.

Facilitated Dissociation of a Nucleoid Protein from the Bacterial Chromosome.

UNLABELLED: Off-rates of proteins from the DNA double helix are widely considered to be dependent only on the interactions inside the initially bound protein-DNA complex and not on the concentration of nearby molecules. However, a number of recent single-DNA experiments have shown off-rates that depend on solution protein concentration, or "facilitated dissociation." Here, we demonstrate that this effect occurs for the major Escherichia coli nucleoid protein Fis on isolated bacterial chromosomes. We isolated E. coli nucleoids and showed that dissociation of green fluorescent protein (GFP)-Fis is controlled by solution Fis concentration and exhibits an "exchange" rate constant (kexch) of ≈10(4) M(-1) s(-1), comparable to the rate observed in single-DNA experiments. We also show that this effect is strongly salt dependent. Our results establish that facilitated dissociation can be observed in vitro on chromosomes assembled in vivo IMPORTANCE: Bacteria are important model systems for the study of gene regulation and chromosome dynamics, both of which fundamentally depend on the kinetics of binding and unbinding of proteins to DNA. In experiments on isolated E. coli chromosomes, this study showed that the prolific transcription factor and chromosome packaging protein Fis displays a strong dependence of its off-rate from the bacterial chromosome on Fis concentration, similar to that observed in in vitro experiments. Therefore, the free cellular DNA-binding protein concentration can strongly affect lifetimes of proteins bound to the chromosome and must be taken into account in quantitative considerations of gene regulation. These results have particularly profound implications for transcription factors where DNA binding lifetimes can be a critical determinant of regulatory function.

ATP hydrolysis enhances RNA recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 (LGP2).

Laboratory of genetics and physiology 2 (LGP2) is a member of the RIG-I-like receptor family of cytoplasmic pattern recognition receptors that detect molecular signatures of virus infection and initiate antiviral signal transduction cascades. The ATP hydrolysis activity of LGP2 is essential for antiviral signaling, but it has been unclear how the enzymatic properties of LGP2 regulate its biological response. Quantitative analysis of the dsRNA binding and enzymatic activities of LGP2 revealed high dsRNA-independent ATP hydrolysis activity. Biochemical assays and single-molecule analysis of LGP2 and mutant variants that dissociate basal from dsRNA-stimulated ATP hydrolysis demonstrate that LGP2 utilizes basal ATP hydrolysis to enhance and diversify its RNA recognition capacity, enabling the protein to associate with intrinsically poor substrates. This property is required for LGP2 to synergize with another RIG-I-like receptor, MDA5, to potentiate IFNß transcription in vivo during infection with encephalomyocarditis virus or transfection with poly(I:C). These results demonstrate previously unrecognized properties of LGP2 ATP hydrolysis and RNA interaction and provide a mechanistic basis for a positive regulatory role for LGP2 in antiviral signaling.