Lopinavir/Ritonavir for COVID-19: a Systematic Review and Meta-Analysis.

PURPOSE: To provide the latest evidence on the efficacy and safety of lopinavir/ritonavir compared to other treatment options for COVID-19. METHODS: We searched PubMed, Cochran Library, Embase, Scopus, and Web of Science for the relevant records up to April 2021. Moreover, we scanned MedRxiv, Google Scholar, and clinical registry databases to identify additional records. We have used the Newcastle-Ottawa Scale and Cochrane risk of bias tools to assess the quality of studies. This Meta-analysis was conducted using RevMan software (version 5.3). RESULTS: Fourteen studies were included. No significant difference was observed between lopinavir/ritonavir and non-antiviral treatment groups in terms of negative rate of PCR (polymerase chain reaction) on day 7 (risk ratio [RR]: 0.83; 95% CI: 0.63 to 1.09; P=0.17), and day 14 (RR: 0.93; 95% CI: 0.81 to 1.05; P=0.25), PCR negative conversion time (mean difference [MD]: 1.09; 95% CI: -0.10 to 2.29; P=0.07), secondary outcomes, and adverse events (P>0.05). There was no significant difference between lopinavir/ritonavir and chloroquine as well as lopinavir/ritonavir and hydroxychloroquine regarding the efficacy outcomes (P>0.05). However, lopinavir/ritonavir showed better efficacy than arbidol for the same outcomes (P<0.05). Lopinavir/ritonavir plus arbidol was effective compared to arbidol alone in terms of the negative rate of PCR on day 7 (P=0.02). However, this difference was not significant regarding other efficacy outcomes (P>0.05). CONCLUSION: Lopinavir/ritonavir has no more treatment effects than other therapeutic agents used herein in COVID-19 patients.

Repurposing metformin for covid-19 complications in patients with type 2 diabetes and insulin resistance.

Understanding the exact role of current drugs in Covid-19 disease is essential in the era of global pandemics. Metformin which prescribed as the first-line treatment of type 2 diabetes has beneficial effects on Sars-cov2 infection. These effects are including regulation of immune system, Renin-Angiotensin System and Dipeptidyl Peptidase 4 function in Covid-19 infection. It also activates ACE2, the main receptor of Sars-cov2, in the epithelial cells of respiratory tissue through AMPK signaling and subsequently decreases the rate of viral adhesion. Metformin also declines the adherence of Sars-cov2 to DPP4 (the other receptor of the virus) on T cells. Hence, regulatory effects of metformin on membranous ACE2, and DPP4 can modulate immune reaction against Sars-cov2. Also, immunometabolic effects of metformin on inflammatory cells impair hyper-reactive immune response against the virus through reduction of glycolysis and propagation of mitochondrial oxidation. Metformin also decreases platelet aggravation and risk of thrombosis. In this article, we argue that metformin has beneficial effects on Covid-19 infection in patients with type 2 diabetes and insulin resistance. This opinion should be investigated in future clinical trials.

1,4-D-Glucan block copolymers: synthesis and comprehensive structural characterization.

Multi-block glucans comprising permethylated and partially methylated blocks are compounds of interest. In order to monitor their formation by transglycosylation of corresponding starting glucans, a method has been developed and applied to model compounds. This method allows determining the average length of the blocks and the progress of incorporation of methyl blocks in partially methylated sequences with a random distribution. The method, comprising liquid chromatography mass spectrometry (LC-MS) and electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MSn) measurements of two types of peralkylated glucans representing derivatives of the target compounds, is comprehensively described and discussed. ESI-MSn allows looking into the sequences of oligomeric domains. In addition, transglycosylation is followed by attenuated total reflection FTIR and NMR spectroscopy. Graphical abstract.

Biomacromolecules as tools and objects in nanometrology-current challenges and perspectives.

Nucleic acids, proteins, and polysaccharides are the most important classes of biopolymers. The inherent properties of biomacromolecules are contrary to those of well-defined small molecules consequently raising a number of specific challenges which become particularly apparent if biomacromolecules are treated as objects in quantitative analysis. At the same time, their specific functional ability of molecular recognition and self-organization (e.g., enzymes, antibodies, DNA) enables us to make biomacromolecules serving as molecular tools in biochemistry and molecular biology, or as precisely controllable dimensional platforms for nanometrological applications. Given the complexity of biomacromolecules, quantitative analysis is not limited to the measurement of their concentration but also involves the determination of numerous descriptors related to structure, interaction, activity, and function. Among the biomacromolecules, glycans set examples that quantitative characterization is not necessarily directed to the measurement of amount-of-substance concentration but instead involves the determination of relative proportions (molar ratios) of structural features for comparison with theoretical models. This article addresses current activities to combine optical techniques such as Raman spectroscopy with isotope dilution approaches to realize reference measurement procedures for the quantification of protein biomarkers as an alternative to mass spectrometry-based techniques. Furthermore, it is explored how established ID-MS protocols are being modified to make them applicable for quantifying virus proteins to measure the HIV viral load in blood samples. As an example from the class of carbohydrates, the challenges in accurate determination of substitution patterns are outlined and discussed. Finally, it is presented that biomacromolecules can also serve as tools in quantitative measurements of dimensions with an example of DNA origami to generate defined dimensional standards to be used for calibration in super-resolution fluorescence microscopy. Graphical abstract Quantitative analysis of biomacromolecules is accompanied with special challenges different from low molecular weight compounds. In addition, they are not only objects but also tools applicable for quantitative measurements.

The impact of piperine on the metabolic conditions of patients with NAFLD and early cirrhosis: a randomized double-blind controlled trial.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic dysfunction of the liver defined as an abnormal accumulation of fat within the liver without secondary triggers like alcohol consumption or viral hepatitis. Piperine, the bio-active ingredient of black pepper, can exert a significant function in treatment of individuals with NAFLDand early cirrhosis. We investigated the impact of piperine consumption with a duration of 12 weeks on patients with NAFLD and early cirrhosis compared toplacebo consumption. In a double-blind study, patients with NAFLD and early stage of cirrhosis were haphazardly distributed into case and control groups. They were prescribed a placebo and 5 mg of piperine for 12 weeks, respectively. The demographic and laboratory parameters of individuals were assessed as the baseline and after the duration of piperine intake. Piperine with a daily dosage of 5 mg could significantly decrease hepatic enzymes and glucose, and alleviate dyslipidemia in the case arm rather than the control arm. Moreover, HOMA levels and insulin resistance were reduced in case participants compared to the control counterparts. In the absence of approved medicinal intervention for patients with NAFLD, and regarding the favorable impact of piperine on NAFLD more studies on this subject are warranted.

Covalently Functionalized MXenes for Highly Sensitive Humidity Sensors.

Transition metal carbides and nitrides (MXenes) are an emerging class of 2D materials, which are attracting ever-growing attention due to their remarkable physicochemical properties. The presence of various surface functional groups on MXenes' surface, e.g., F, O, OH, Cl, opens the possibility to tune their properties through chemical functionalization approaches. However, only a few methods have been explored for the covalent functionalization of MXenes and include diazonium salt grafting and silylation reactions. Here, an unprecedented two-step functionalization of Ti3 C2 Tx MXenes is reported, where (3-aminopropyl)triethoxysilane is covalently tethered to Ti3 C2 Tx and serves as an anchoring unit for subsequent attachment of various organic bromides via the formation of CN bonds. Thin films of Ti3 C2 Tx functionalized with linear chains possessing increased hydrophilicity are employed for the fabrication of chemiresistive humidity sensors. The devices exhibit a broad operation range (0-100% relative humidity), high sensitivity (0.777 or 3.035), a fast response/recovery time (0.24/0.40 s ΔH-1 , respectively), and high selectivity to water in the presence of saturated vapors of organic compounds. Importantly, our Ti3 C2 Tx -based sensors display the largest operating range and a sensitivity beyond the state of the art of MXenes-based humidity sensors. Such outstanding performance makes the sensors suitable for real-time monitoring applications.

Ultrathin positively charged electrode skin for durable anion-intercalation battery chemistries.

The anion-intercalation chemistries of graphite have the potential to construct batteries with promising energy and power breakthroughs. Here, we report the use of an ultrathin, positively charged two-dimensional poly(pyridinium salt) membrane (C2DP) as the graphite electrode skin to overcome the critical durability problem. Large-area C2DP enables the conformal coating on the graphite electrode, remarkably alleviating the electrolyte. Meanwhile, the dense face-on oriented single crystals with ultrathin thickness and cationic backbones allow C2DP with high anion-transport capability and selectivity. Such desirable anion-transport properties of C2DP prevent the cation/solvent co-intercalation into the graphite electrode and suppress the consequent structure collapse. An impressive PF6--intercalation durability is demonstrated for the C2DP-covered graphite electrode, with capacity retention of 92.8% after 1000 cycles at 1 C and Coulombic efficiencies of > 99%. The feasibility of constructing artificial ion-regulating electrode skins with precisely customized two-dimensional polymers offers viable means to promote problematic battery chemistries.

Electrochemical Exfoliation to Produce High-Quality Black Phosphorus.

To obtain high-quality two-dimensional (2D) materials from the bulky crystals, delamination under an externally controlled stimulus is crucial. Electrochemical exfoliation of layered materials requires simple instrumentation yet offers high-quality exfoliated 2D materials with high yields and features straightforward upscalability; therefore, it represents a key technology for advancing fundamental studies and industrial applications. Moreover, the solution processability of functionalized 2D materials enables the fabrication of (opto)electronic and energy devices via different printing technologies such as inkjet printing and 3D printing. This paper presents the electrochemical exfoliation protocol for the synthesis of black phosphorus (BP), one of the most promising emerging 2D materials, from its bulk crystals in a step-by-step manner, namely, cathodic electrochemical exfoliation of BP in the presence of N(C4H9)4∙HSO4 in propylene carbonate, dispersion preparation by sonication and subsequent centrifugation for the separation of flakes, and morphological characterization by scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM).

NETosis in ischemic/reperfusion injuries: An organ-based review.

Neutrophil extracellular trap (NETosis), the web-like structures induced by neutrophil death, is an important inflammatory mechanism of the immune system leading to reactive oxygen species production/coagulopathy, endothelial dysfunction, atherosclerosis, and ischemia. NETosis exerts its role through different mechanisms such as triggering Toll-like receptors, inflammatory cytokines, platelet aggregation, neutrophil activation/infiltration, and vascular impairment. NETosis plays a key role in the prognosis of coronary artery disease, ischemic injury of kidney, lung, gastrointestinal tract and skeletal muscles. In this review, we explored the molecular mechanisms involved in NETosis, and ischemic/reperfusion injuries in body organs.

Evaluation of NUF2 and GMNN Expression in Prostate Cancer: Potential Biomarkers for Prostate Cancer Screening.

BACKGROUND: Prostate cancer (PC) is one of the most abundant cancers among men, and In Iran, has been responsible for 6% of all deaths from cancer in men. NUF2 and GMNN genes are considered as loci of susceptibility to tumorigenesis in humans. Alterations in expression of these genes have been reported in various malignancies. The aim of our study was to test whether different NUF2 and GMNN expression levels are associated with PC incidence and hence, might be considered as new molecular tools for PC screening. METHODS: Biopsy samples from 40 PC patients and 41 healthy Iranian men were used to determine the relative gene expression. After RNA extraction and cDNA synthesis, samples were analyzed using TaqMan Quantitative Real time PCR. Patients' background information, included smoking habits and family histories of PC, were recorded. Stages and grades of their PC were classified by the TNM tumor, node, metastasis (TMN) staging system based on standard guidelines. RESULTS: NUF2 expression did not significantly differ between the groups, while GMNN expression was significantly greater in the PC specimens than in the controls. CONCLUSION: Regarding the significant role of GMNN in various tumor phenotypes, and its importance in PC progression, the alteration in GMNN expression in PC samples vs. controls indicate that the genetic profiling of this cancer might be considered to personalize therapy for each patient in the future.

Comprehensive structural analysis of a set of various branched glucans by standard methylation analysis, 1H NMR spectroscopy, ESI-mass spectrometry, and capillary electrophoresis.

Various (semi)-synthetic non-digestible glucans (NDG) (resistant (malto)dextrin, isomaltooligosaccharide, soluble corn fiber, polydextrose) were analyzed by methylation analysis, 1H NMR spectroscopy, ESI-MSn, TLC, and capillary electrophoresis (CE/UV). Partly complementary and partly corroborative results were obtained by these methods yielding a comprehensive overview about the various degrees of complexity and special structural features. Methylation analysis enabled the most detailed quantitative evaluation of glycosidic linkage positions and branching pattern, and detection of furanosyl residues. 1H NMR spectroscopy provided additional information on anomeric configuration. By ESI-IT-MS up to DP 13, for doubly charged up to DP 22 was detected. Glucitol residues in polydextrose as well as anhydrosugar formation in thermally treated glucans could also be recognized from the mass spectra. Furthermore, MS2 of the disaccharide portion gave insights into the linkage positions present in the glucan mixture. Electrophoresis of ANTS-labeled oligosaccharides showed the DP-resolved differences of complexity and was the most powerful method to identify the type of glucan by its CE-fingerprint. The aim was to present complementary analytical data obtained by application of identical conditions and methods to a wide range of NDG with increasing complexity to allow direct structure comparison.