UPLC-PDA factorial design assisted method for simultaneous determination of oseltamivir, dexamethasone, and remdesivir in human plasma.

A green and simple UPLC method was developed and optimized, adopting a factorial design for simultaneous determination of oseltamivir phosphate and remdesivir with dexamethasone as a co-administered drug in human plasma and using daclatasvir dihydrochloride as an internal standard within 5 min. The separation was established on UPLC column BEH C18 1.7 µm (2.1 × 100.0 mm) connected to UPLC pre-column BEH 1.7 µm (2.1 × 5.0 mm) at 50 °C with an injection volume of 10 µL. The photodiode array detector (PDA) was set at three wavelengths of 220, 315, and 245 nm for oseltamivir phosphate, the internal standard, and both dexamethasone and remdesivir, respectively. The mobile phase consisted of methanol and ammonium acetate solution (40 mM) adjusted to pH 4 in a ratio of 61.5:38.5 (v/v) with a flow rate of 0.25 mL min-1. The calibration curves were linear over 500.0-5000.0 ng mL-1 for oseltamivir phosphate, over 10.0-500.0 ng mL-1 and 500.0-5000.0 ng mL-1 for dexamethasone, and over 20.0-500 ng mL-1 and 500.0-5000.0 ng mL-1 for remdesivir. The Gibbs free energy and Van't Hoff plots were used to investigate the effect of column oven temperatures on retention times. Fluoride-EDTA anticoagulant showed inhibition activity on the esterase enzyme in plasma. The proposed method was validated according to the M10 ICH, FDA, and EMA's bioanalytical guidelines. According to Eco-score, GAPI, and AGREE criteria, the proposed method was considered acceptable green.

Lab-on-a-lollipop (LoL) platform for preventing food-induced toxicity: all-in-one system for saliva sampling and electrochemical detection of vanillin.

Saliva has emerged as a primary biofluid for non-invasive disease diagnostics. Saliva collection involves using kits where individuals stimulate saliva production via a chewing device like a straw, then deposit the saliva into a designated collection tube. This process may pose discomfort to patients due to the necessity of producing large volumes of saliva and transferring it to the collection vessel. This work has developed a saliva collection and analysis device where the patient operates it like a lollipop, stimulating saliva production. The lollipop-mimic device contains yarn-based microfluidic channels that sample saliva and transfer it to the sensing zone embedded in the stem of the device. We have embedded electrochemical sensors in the lollipop platform to measure vanillin levels in saliva. Vanillin is the most common food flavoring additive and is added to most desserts such as ice cream, cakes, and cookies. Overconsumption of vanillin can cause side effects such as muscle weakness, and damage to the liver, kidneys, stomach, and lungs. We detected vanillin using direct oxidation at a laser-induced graphene (LIG) electrode. We showed a dynamic range of 2.5 µM to 30 µM, covering the physiologically relevant concentration of vanillin in saliva. The lab-on-a-lollipop platform requires only 200 µL of saliva and less than 2 minutes to fill the channels and complete the measurement. This work introduces the first sensor-embedded lollipop-mimic saliva collection and measurement system.

Various investigations of ameliorative role of Ashwagandha seeds (Withania somnifera) against amoxicillin toxicity.

Several studies showed the adverse effects of amoxicillin on various body organs. So, this research has been designed to evaluate the modulatory role of Ashwagandha seed extract (ASE) against amoxicillin (AM) toxicity. Rats treated with AM (90 mg/kg), protected by ASE doses (100, 200 and 300 mg/kg), and treated by ASE at the same three doses. At the end of the experimental period, DNA comet assay, cytogenetic examinations, sperm-shape analysis, evaluation of the malondialdehyde (MDA) percentages, histopathological examinations, and biophysical tests (modulus, relaxation time, permittivity, entropy, and internal energy change of brain) were documented. The results confirmed that AM treatment induced significant elevation of DNA damage, cytogenetic aberrations, and MDA content in brain, liver, and testis tissues and sperm-shape anomalies. ASE treatment significantly minimized the genetic changes, sperm-shape anomalies, and MDA generation. These enhancements were more pronounced by protective ASE and increased by increasing the dose level. In histopathological examinations, AM treatment caused neurotoxicity in brain tissue. ASE treatment, partially, minimized these damages and the positive effects of therapeutic ASE were more noticeable. Biophysical parameters showed that therapeutic ASE was better for relaxation time, permittivity, and free energy change. Protective and therapeutic ASE were able to recover entropy and internal energy changes in variant degrees.

Toward an Improved Electrocatalytic Determination of Immunomodulator COVID Medication Baricitinib Using Multiwalled Carbon Nanotube Nickel Hybrid.

The study presents a first electrochemical method for the determination of the immunomodulator drug Baricitinib (BARI), crucial in managing COVID-19 patients requiring oxygen support. A unique electrode was developed by modifying graphite carbon nickel nanoparticles (NiNPs) with functionalized multiwalled carbon nanotubes (f.MWCNTs), resulting in nanohybrids tailored for highly sensitive BARI detection. Comparative analysis revealed the superior electrocatalytic performance of the nanohybrid-modified electrode over unmodified counterparts and other modifications, attributed to synergistic interactions between f.MWCNTs and nickel nanoparticles. Under optimized conditions, the sensors exhibited linear detection within a concentration range from 4.00 × 10-8 to 5.56 × 10-5 M, with a remarkably low detection limit of 9.65 × 10-9 M. Notably, the modified electrode displayed minimal interference from common substances and demonstrated high precision in detecting BARI in plasma and medicinal formulations, underscoring its clinical relevance and potential impact on COVID-19 treatment strategies.

Corrigendum: Deciphering decidual leukocyte traffic with serial intravascular staining.

[This corrects the article DOI: 10.3389/fimmu.2023.1332943.].

Numerical analysis for tangent-hyperbolic micropolar nanofluid flow over an extending layer through a permeable medium.

The principal purpose of the current investigation is to indicate the behavior of the tangent-hyperbolic micropolar nanofluid border sheet across an extending layer through a permeable medium. The model is influenced by a normal uniform magnetic field. Temperature and nanoparticle mass transmission is considered. Ohmic dissipation, heat resource, thermal radiation, and chemical impacts are also included. The results of the current work have applicable importance regarding boundary layers and stretching sheet issues like rotating metals, rubber sheets, glass fibers, and extruding polymer sheets. The innovation of the current work arises from merging the tangent-hyperbolic and micropolar fluids with nanoparticle dispersal which adds a new trend to those applications. Applying appropriate similarity transformations, the fundamental partial differential equations concerning speed, microrotation, heat, and nanoparticle concentration distributions are converted into ordinary differential equations, depending on several non-dimensional physical parameters. The fundamental equations are analyzed by using the Rung-Kutta with the Shooting technique, where the findings are represented in graphic and tabular forms. It is noticed that heat transmission improves through most parameters that appear in this work, except for the Prandtl number and the stretching parameter which play opposite dual roles in tin heat diffusion. Such an outcome can be useful in many applications that require simultaneous improvement of heat within the flow. A comparison of some values of friction with previous scientific studies is developed to validate the current mathematical model.

Green ecofriendly electrochemical sensing platform for the sensitive determination of doxycycline.

The detection of pharmaceutical compounds in extremely low concentrations remains a challenge despite recent advancements in electrochemical sensing. In this study, a green hydrothermally synthesized nickel hydroxide-graphene hybrid material was used for the point-of-care determination of the antibiotic doxycycline (DOXY), which is a promising treatment for COVID-19 and other infections. The electrochemical sensor, based on a screen-printed electrode modified with the hybrid material, was able to detect DOXY in the range of 5.1 × 10-8 to 1.0 × 10-4 M, with a low detection limit of 9.6 × 10-9 M. This approach paves the way for eco-friendly and sustainable methods of nanomaterial synthesis for electrochemical analyses, particularly in point-of-care drug monitoring, and has the potential to improve access to testing platforms.

Development of UPLC method for simultaneous assay of some COVID-19 drugs utilizing novel instrumental standard addition and factorial design.

A green, rapid, and simple RP-UPLC method was developed and optimized by full factorial design for the simultaneous separation of oseltamivir phosphate, daclatasivir dihydrochloride, and remdesivir, with dexamethasone as a co-administered drug. The separation was established on a UPLC column BEH C18 1.7 µm (2.1 × 100.0 mm) connected with a UPLC pre-column BEH 1.7 µm (2.1 × 5.0 mm) at 25 °C with an injection volume of 10 µL. The detector (PDA) was set at 239 nm. The mobile phase consisted of methanol and ammonium acetate (8.1818 mM) in a ratio of 75.7: 24.3 (v/v). The flow rate was set at 0.048 mL min-1. The overall separation time was 9.5 min. The retention times of oseltamivir phosphate, dexamethasone, daclatasivir dihydrochloride, and remdesivir were 6.323 ± 0.145, 7.166 ± 0.036, 8.078 ± 0.124, and 8.572 ± 0.166 min (eight replicates), respectively. The proposed method demonstrated linearity in the ranges of 10.0-500.0 (ng mL-1) and 0.5-30.0 (µg mL-1) for oseltamivir phosphate, 50.0-5000.0 (ng mL-1) for dexamethasone, 25.0-1000.0 (ng mL-1) and 0.5-25.0 (µg mL-1) for daclatasvir dihydrochlorde, and 10.0-500.0 (ng mL-1) and 0.5-30.0 (µg mL-1) for remdesivir. The coefficients of determination (R2) were greater than 0.9999, with percentage recoveries greater than 99.5% for each drug. The limits of quantitation were 6.4, 1.8, 7.8, and 1.6 ng mL-1, and the limits of detection were 1.9, 0.5, 2.0, and 0.5 ng mL-1 for oseltamivir phosphate, dexamethasone, daclatasivir dihydrochloride, and remdesivir, respectively. The proposed method was highly precise, as indicated by the low percentage of relative standard deviation values of less than 1.2% for each drug. The average content and uniformity of dosage units in the studied drugs' dosage forms were determined. The average contents of oseltamivir phosphate, dexamethasone, daclatasivir dihydrochloride, and remdesivir were nearly 93%, 102%, 99%, and 95%, respectively, while the uniformity of dosage unit values were nearly 92%, 102%, 101%, and 97%. Two novel methods were established in this work. The first method was used to assess the stability of standard solutions. This novel method was based on the slope of regression equations. The second was to evaluate the excipient's interference using an innovative instrumental standard addition method. The novel instrumental standard addition method was performed using the UPLC instrument program. It was more accurate, sensitive, time-saving, economical, and eco-friendly than the classic standard addition method. The results showed that the proposed method can estimate the tested drugs' concentrations without interference from their dosage form excipients. According to the Eco-score (more than 75), the Green Analytical Procedure Index (GAPI), and the AGREE criteria (total score of 0.77), the suggested method was considered eco-friendly.

Peristaltic transport of Rabinowitsch nanofluid with moving microorganisms.

The key objective of the current examination is to examine a symmetrically peristaltic movement of microorganisms in a Rabinowitsch fluid (RF). The Boussinesq approximation, buoyancy-driven flow, where the density with gravity force term is taken as a linear function of heat and concentrations, is kept in mind. The flow moves with thermophoretic particle deposition in a horizontal tube with peristalsis. The heat distribution and volume concentration are revealed by temperature radiation and chemical reaction characteristics. The originality of the existing study arises from the importance of realizing the benefits or the threats that nanoparticles, microbes, and bacteria cause in the flow inside peristaltic tubes. The results are an attempt to understand what factors perform additional advantages and or reduce damages. The controlling nonlinear partial differential equations (PDEs) are made simpler by employing the long wavelength (LWL) and low-Reynolds numeral (LRN) approximations. These equations are subjected to a set of non-dimensional transformations that result in a collection of nonlinear ordinary differential equations (ODEs). By employing the Homotopy perturbation method (HPM), the configuration of equational analytical solutions is examined. Analytical and graphical descriptions are provided for the distributions of axial speed, heat, microbes, and nanoparticles under the influence of these physical characteristics. The important findings of the current work may help to comprehend the properties of several variations in numerous biological situations. It is found that the microorganisms condensation decays with the rise of all the operational parameters. This means that the development of all these factors benefits in shrinking the existence of harmful microbes, viruses, and bacteria in the human body's peristaltic tubes, especially in the digestive system, and large and small intestines.

Sensitive and effective electrochemical determination of butenafine in the presence of itraconazole using titanium nanoparticles-ionic liquid based nanocomposite sensor.

The evaluation of the bioavailability of topically applied medications that act inside or under the skin is a challenging task. Herein, the current study describes a simple, quick, and low-cost electrochemical platform for determining butenafine hydrochloride (BTH) that is mainly prescribed as a treatment of dermatophytosis, applying titanium nanoparticles and an ionic liquid as outstanding mediators. In terms of low detection limits (61.63 nM) and extensive range of 2.21 × 10-7-13.46 × 10-5 M, the established electrochemical technique provided worthy analytical performance for butenafine hydrochloride sensing. The suggested sensor's practical applicability was effectively demonstrated in pharmaceutical preparations, actual stratum corneum samples, and simultaneous detection of butenafine hydrochloride and Itraconazole in pharmaceutical preparation for the first time. All of the experimental factors, like the pH and scan rate, have been investigated and optimized. Diffusion coefficients of butenafine hydrochloride at bare and modified sensors were calculated. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02593-3.

Deciphering decidual leukocyte traffic with serial intravascular staining.

The decidual immunome is dynamic, dramatically changing its composition across gestation. Early pregnancy is dominated by decidual NK cells, with a shift towards T cells later in pregnancy. However, the degree, timing, and subset-specific nature of leukocyte traffic between the decidua and systemic circulation during gestation remains poorly understood. Herein, we employed intravascular staining in pregnant C57BL/6J mice and cynomolgus macaques (Macaca fascicularis) to examine leukocyte traffic into the decidual basalis during pregnancy. Timed-mated or virgin mice were tail-vein injected with labelled αCD45 antibodies 24 hours and 5 minutes before sacrifice. Pregnant cynomolgus macaques (GD155) were infused with labelled αCD45 at 2 hours or 5 mins before necropsy. Decidual cells were isolated and resulting suspensions analyzed by flow cytometry. We found that the proportion of intravascular (IVAs)-negative leukocytes (cells labeled by the 24h infusion of αCD45 or unlabeled) decreased across murine gestation while recent immigrants (24h label only) increased in mid- to late-gestation. In the cynomolgus model our data confirmed differential labeling of decidual leukocytes by the infused antibody, with the 5 min infused animal having a higher proportion of IVAs+ cells compared to the 2hr infused animal. Decidual tissue sections from both macaques showed the presence of intravascularly labeled cells, either in proximity to blood vessels (5min infused animal) or deeper into decidual stroma (2hr infused animal). These results demonstrate the value of serial intravascular staining as a sensitive tool for defining decidual leukocyte traffic during pregnancy.

Heat and mass flux through a Reiner-Rivlin nanofluid flow past a spinning stretching disc: Cattaneo-Christov model.

The current work scrutinizes a non-Newtonian nanofluid free convective flow induced by a rotating stretchable disc. The examination surveys the Stefan blowing and Cattaneo-Christov mass and heat fluxes, as a precise illustrative model. The innovative aspects of the ongoing project include the analysis of the border sheet nanofluid flow near a revolving disc through thermophoresis, Reiner-Rivlin prototype features, and random nanoparticle motion. The Reiner-Rivlin non-Newtonian model is considered together with the effect of an unvarying axial magnetic strength. The constitutive formulae of a Reiner-Rivlin liquid have been reproduced in the cylindrical coordinates. Through implementing the applicable relationship transformations, the controlling partial differential equations are transferred to ordinary differential equations (ODE). This procedure yields a group of coupled nonlinear ordinary differential equations in relation to speed, heat, and nanoparticle concentration profiles that are impacted by several physical characteristics. These equations are analyzed by using the homotopy perturbation method (HPM). Due to the analytical solution given by HPM, the current work enables us to take the infinity of the layer as a parameter of the problem and discuss its variation in the obtained distributions. Consequently, a physical significant graphical visualization of the data is emphasized. The rates of mass and temperature transmission are examined to understand if any of the relevant parameters may improve these rates. Additionally, the Stefan blowing causes extra particles diffusion, which enhances heat transfer and raises the nanoparticles concentration and could be useful in some medical therapies. Furthermore, the stretching of the rotating disc is concluded, which improves the fluid heat transfer.

A Casson nanofluid flow within the conical gap between rotating surfaces of a cone and a horizontal disc.

The present study highlights the flow of an incompressible nanofluid following the non-Newtonian flow. The non-Newtonian fluid behavior is characterized by the Casson prototype. The flow occupies the conical gap between the rotating/stationary surfaces of the cone and the horizontal disc. Heat and mass transfer is also considered. The novelty of the proposed mathematical model is supplemented with the impacts of a uniform magnetic field imposed vertically upon the flow together with Ohmic dissipation and chemical reactions. The constitutive equations of the Casson fluid have been interpreted along with the cylindrical coordinates. The governing partial differential equations of momentum, energy, and concentration are converted into a set of nonlinear ordinary differential equations via appropriate similarity transformations. This scheme leads to a set of coupled nonlinear ordinary equations concerning velocity, temperature, and nanoparticles concentration distributions. These equations are analytically solved by means of the Homotopy perturbation method (HPM). The theoretical findings are presented in both graphical and tabular forms. The main objective of this study is to discuss the effects of the rotations of both cone and disc and the effects of the other parameters in the two cases of rotation alternatively. Additionally, the effect of the angle between the cone and the disk is one of our interesting points because of the importance of its effect in some engineering industry applications. The rotation parameters are found to have reduction effects on both the temperature and the radial velocity of the fluid, while they have an enhancing effect on the azimuthal velocity. The effects of other parameters with these rotations are found to be qualitatively the same as some earlier published studies. To validate the current mathematical model, a comparison with the previous scientific reports is made.

Protective effect of copper II-albumin complex against aflatoxin B1- induced hepatocellular toxicity: The impact of Nrf2, PPAR-γ, and NF-kB in these protective effects.

Copper II-Albumin complex (Cu-II-Albumin complex) is a novel therapeutic target that has been used as anti-inflammatory, antioxidant, and anti-gastrointestinal toxicity. In this study, 40 rats were divided into four groups, normal control (NC), aflatoxicosed group (AF) that received Aflatoxin B1 (AFB1) (50 µg/kg of the AFB1 daily for 3 weeks), AFB1-Cu-II-Albumin prophylactic group (AF/CUC-P) that subjected to intermittent treatment between AFB1 and Cu-II-Albumin complex (0.05 g/kg Cu-II-Albumin complex) day after day for 3 weeks and AFB1-Cu-II-albumin treatment group (AF/CUC-T) that received AFB1 for 3 weeks and Cu-II-albumin complex for another 3 weeks. The hepatocellular protective effect of the Cu-II-albumin complex was assessed by evaluating the liver functions markers, hepatic histopathology, reactive oxygen species (ROS) levels (Nitric Oxide (NO) and malondialdehyde (MDA)), apoptotic genes (caspase-3 and tumor necrosis factor receptor 1 [TNF-R1]) expressions, and serological and molecular biomarkers of hepatocellular carcinoma (histamine and Glucose-Regulated Protein 78 [GRP78], respectively). Our finding showed that Cu-II-Albumin Complex administration had restored liver function, oxidative stress levels, enhanced liver tissue recovery, and reduced the expression of the apoptotic genes of the aflatoxicosed rats. In conclusion, the current study results demonstrated the protective effect of Cu-II-albumin complex against AFB1-induced hepatocellular toxicity. PRACTICAL APPLICATIONS: The protective effect of Cu-II-Albumin Complex against AFB1-induced hepatocellular toxicity by assessing oxidative stress, liver biomarkers, inflammation, and histological changes of liver tissues. The protective mechanism of the Cu-II-albumin complex was also investigated. More clinical studies are required to evaluate the potential of using the Cu-II-albumin complex as a therapeutic agent against hepatocellular toxicity.

Clinical role of MiRNA 29a and MiRNA 335 on breast cancer management: their relevance to MMP2 protein level.

BACKGROUND: Circulating miRNAs are novel biomarkers, authors aimed to investigate the expression level of miR-29a and miR-335 and their relevance to CEA, CA15.3, and matrix metalloproteinase-2 (MMP2). MATERIALS AND METHODS: Breast cancer (BC) patients (n = 44), benign breast lesion patients (n = 25), and healthy individuals (n = 19) were enrolled for detection of miRNA expression levels, MMP2 and biochemical markers using quantitative polymerase chain reaction (PCR) and ELISA, respectively. RESULTS: Expression of miR-29a and miR-335 were significantly decreased in breast patients as compared to healthy individuals, while biochemical markers were high in BC patients as compared to the other two groups. The diagnostic efficacy for miR-29a, miR-335, and MMP2 were superior to both CEA and CA 15.3 for early detection of BC patients. CONCLUSIONS: Detection of the miR-29a and miR335 expression levels in serum samples are significant promising biomarkers for BC diagnosis.

Optical Biosensors for Diagnostics of Infectious Viral Disease: A Recent Update.

The design and development of biosensors, analytical devices used to detect various analytes in different matrices, has emerged. Biosensors indicate a biorecognition element with a physicochemical analyzer or detector, i.e., a transducer. In the present scenario, various types of biosensors have been deployed in healthcare and clinical research, for instance, biosensors for blood glucose monitoring. Pathogenic microbes are contributing mediators of numerous infectious diseases that are becoming extremely serious worldwide. The recent outbreak of COVID-19 is one of the most recent examples of such communal and deadly diseases. In efforts to work towards the efficacious treatment of pathogenic viral contagions, a fast and precise detection method is of the utmost importance in biomedical and healthcare sectors for early diagnostics and timely countermeasures. Among various available sensor systems, optical biosensors offer easy-to-use, fast, portable, handy, multiplexed, direct, real-time, and inexpensive diagnosis with the added advantages of specificity and sensitivity. Many progressive concepts and extremely multidisciplinary approaches, including microelectronics, microelectromechanical systems (MEMSs), nanotechnologies, molecular biology, and biotechnology with chemistry, are used to operate optical biosensors. A portable and handheld optical biosensing device would provide fast and reliable results for the identification and quantitation of pathogenic virus particles in each sample. In the modern day, the integration of intelligent nanomaterials in the developed devices provides much more sensitive and highly advanced sensors that may produce the results in no time and eventually help clinicians and doctors enormously. This review accentuates the existing challenges engaged in converting laboratory research to real-world device applications and optical diagnostics methods for virus infections. The review's background and progress are expected to be insightful to the researchers in the sensor field and facilitate the design and fabrication of optical sensors for life-threatening viruses with broader applicability to any desired pathogens.

Sensitive Determination of SARS-COV-2 and the Anti-hepatitis C Virus Agent Velpatasvir Enabled by Novel Metal-Organic Frameworks.

Herein, we report on the electrochemical determination of velpatasvir (VLP) as the main constituent of Epclusa, a SARS-COV-2 and anti-hepatitis C virus (HCV) agent, using a novel metal-organic framework (MOF). The NH2-MIL-53(Al) MOF was successfully modified with 5-bromo-salicylaldehyde to synthesize 5-BSA=N-MIL-53(Al) MOF. The synthesized MOF has been characterized using Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electron microscopy, cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy. The modified MOF showed higher electrochemical activity and response than the bare NH2-MIL-53(Al) MOF. Compared to the bare carbon paste electrode (CPE), the 5-BSA=N-MIL-53(Al)/CPE platform was shown to enhance the electrochemical oxidation and detection of the anti-SARS-COV-2 and anti-HCV agent. Under optimized conditions, the 5-BSA=N-MIL-53(Al)/CPE platform showed a linear range of 1.11 × 10-6 to 1.11 × 10-7 and 1.11 × 10-7 to 25.97 × 10-6 M Britton-Robinson buffer (pH 7) with a detection limit and limit of quantification of 8.776 × 10-9 and 2.924 × 10-8 M, respectively. Repeatability, storage stability, and reproducibility in addition to selectivity studies and interference studies were conducted to illustrate the superiority of the electrode material. The study also included a highly accurate platform for the determination of VLP concentrations in both urine and plasma samples with reasonable recovery.

Impact of combined therapy of mesenchymal stem cells and sitagliptin on a metabolic syndrome rat model.

BACKGROUND: Emerging evidence suggests that mesenchymal stem cells (MSCs) have many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of many diseases including metabolic syndrome (MetS). However, a major difficulty with stem cell therapy is to maintain cell viability, properties and function after implantation in vivo. This study aims to test the hypothesis that the combined therapy of MSCs and sitagliptin can effectively ameliorate MetS complications induced by high-fat and high-fructose diet (HFFD) in rats. METHODS: Rats were fed either standard diet (Control group) or HFFD. After 3 months, a group of HFFD animals was injected by a single dose of MSCs, another group received a daily oral dose of 10 mg/kg b.w. of sitagliptin, and the third group received the combined therapy of MSCs + sitagliptin for 1 month. RESULTS: Both MSCs and sitagliptin restored insulin sensitivity and reduced the HOMA-IR value in HFFD rats. The hepatic IRS-1 and Akt at both gene and protein levels, as well as the hepatic protein levels of IR and GLUT4 were improved. Downregulation of CHOP and NF-κB and upregulation of hepatic HO-1 expression and activity were also reported. Although MSCs and sitagliptin as monotherapy lead to remarkable effects, the dual application revealed the best results. Interestingly, histological findings confirmed these protective effects of the combined therapy against MetS complications. CONCLUSION: Combined therapy of MSCs and sitagliptin can efficiently ameliorate the insulin resistance and promote the regeneration of hepatocytes in the metabolic syndrome rat model.

Innovative electrochemical sensor for the precise determination of the new antiviral COVID-19 treatment Favipiravir in the presence of coadministered drugs.

Due the current pandemic of COVID-19, an urgent need is required for serious medical treatments of a huge number of patients. The world health organization (WHO) approved Favipiravir (FAV) as a medication for patients infected with corona virus. In the current study, we report the first simple electrochemical, greatly sensitive sensor using MnO2-rGO nanocomposite for the accurate determination of Favipiravir (FAV). The developed sensor showed a high improvement in the electrochemical oxidation of FAV comparing to the unmodified screen-printed electrode (SPE). The suggested platform constituents and the electrochemical measurements parameters were studied. Under optimal experimental parameters, a current response to the concentration change of FAV was found to be in the linear range of 1.0 × 10-8-5.5 × 10-5 M at pH 7.0 with a limit of detection 0.11 µM and a quantification limit of 0.33 µM. The developed platform was confirmed by the precise analysis of FAV in real samples including dosage form and plasma. The developed platform can be applied in different fields of industry quality control and clinical analysis laboratories for the FAV determination.

Epidemiological and genetic characteristics of asymptomatic canine leishmaniasis and implications for human Leishmania infections in Egypt.

Leishmaniasis is a neglected zoonotic disease that poses significant veterinary and public health risks in developing countries. Dogs act as a reservoir host for leishmaniasis transmitted to humans. A total of 108 human cases of cutaneous leishmaniasis (CL) were identified in the Al-Houd Al-Marsoud Hospital in Cairo, Egypt, during 2018. Blood samples and skin biopsies were collected for further examination. Blood samples from 96 asymptomatic dogs were collected. All samples were subjected to molecular and phylogenetic analysis. Quantitative RT-PCR was used to measure the expression of genes related to mTOR signalling and inflammation in blood and tissue samples. The distribution pattern of human cases pointed to an endemic focus in North Sinai (66.67%). The prevalence of asymptomatic canine leishmaniasis was 66.60%. Histopathological examination of human skin lesions revealed a severe granulomatous inflammatory reaction, necrosis and ulceration. Moreover, leishmanial amastigotes could be detected in human tissue samples. Phylogenetic analysis revealed 100% identity of human isolates to Leishmania tropica (MN453682), and dog isolates to Leishmania infantum (MN453673), with 94.9% similarity between the two isolates. Gene expression related to mTOR signalling and inflammation in both species' samples confirmed a significant alteration of EIF4EBP1, CCR4 and INF-γ expression compared with control groups. In Egypt, increased incidence of asymptomatic carrier dogs acting as a significant reservoir host for Leishmania poses a public health hazard. Findings warrant further epidemiological investigation of CL in Egypt, as well as additional study of parasite differentiation and gene regulation.