Experimental investigation for nonalcoholic fatty pancreas management using probiotics.

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) presents a pressing challenge within the domain of metabolic disorders, necessitating further exploration to unveil its molecular intricacies and discover effective treatments. Our focus was to delve into the potential therapeutic impact of ZBiotic, a specially engineered strain of probiotic B. subtilis, in managing NAFP by targeting specific genes linked with necroptosis and the TNF signaling pathway, including TNF, ZBP1, HSPA1B, and MAPK3, along with their upstream epigenetic regulator, miR-5192, identified through bioinformatics. METHODS: Rats were subjected to either a standard or high-fat, high-sucrose diet (HFHS) for eight weeks. Subsequently, they were divided into groups: NAFP model, and two additional groups receiving daily doses of ZBiotic (0.5 ml and 1 ml/kg), and the original B. subtilis strain group (1 ml/kg) for four weeks, alongside the HFHS diet. RESULTS: ZBiotic exhibited remarkable efficacy in modulating gene expression, leading to the downregulation of miR-5192 and its target mRNAs (p < 0.001). Treatment resulted in the reversal of fibrosis, inflammation, and insulin resistance, evidenced by reductions in body weight, serum amylase, and lipase levels (p < 0.001), and decreased percentages of Caspase and Nuclear Factor Kappa-positive cells in pancreatic sections (p < 0.01). Notably, high-dose ZBiotic displayed superior efficacy compared to the original B. subtilis strain, highlighting its potential in mitigating NAFP progression by regulating pivotal pancreatic genes. CONCLUSION: ZBiotic holds promise in curbing NAFP advancement, curbing fibrosis and inflammation while alleviating metabolic and pathological irregularities observed in the NAFP animal model. This impact was intricately linked to the modulation of necroptosis/TNF-mediated pathway-related signatures.

Comprehensive machine learning models for predicting therapeutic targets in type 2 diabetes utilizing molecular and biochemical features in rats.

Introduction: With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need to discover effective therapeutic targets for this complex condition. Coding and non-coding RNAs, with traditional biochemical parameters, have shown promise as viable targets for therapy. Machine learning (ML) techniques have emerged as powerful tools for predicting drug responses. Method: In this study, we developed an ML-based model to identify the most influential features for drug response in the treatment of type 2 diabetes using three medicinal plant-based drugs (Rosavin, Caffeic acid, and Isorhamnetin), and a probiotics drug (Z-biotic), at different doses. A hundred rats were randomly assigned to ten groups, including a normal group, a streptozotocin-induced diabetic group, and eight treated groups. Serum samples were collected for biochemical analysis, while liver tissues (L) and adipose tissues (A) underwent histopathological examination and molecular biomarker extraction using quantitative PCR. Utilizing five machine learning algorithms, we integrated 32 molecular features and 12 biochemical features to select the most predictive targets for each model and the combined model. Results and discussion: Our results indicated that high doses of the selected drugs effectively mitigated liver inflammation, reduced insulin resistance, and improved lipid profiles and renal function biomarkers. The machine learning model identified 13 molecular features, 10 biochemical features, and 20 combined features with an accuracy of 80% and AUC (0.894, 0.93, and 0.896), respectively. This study presents an ML model that accurately identifies effective therapeutic targets implicated in the molecular pathways associated with T2DM pathogenesis.

Modelling dynamics between free-living amoebae and bacteria.

Free-living amoebae (FLA) serve as hosts for a variety of endosymbionts, which are microorganisms that reside and multiply within the FLA. Some of these endosymbionts pose a pathogenic threat to humans, animals, or both. The symbiotic relationship with FLA not only offers these microorganisms protection but also enhances their survival outside their hosts and assists in their dispersal across diverse habitats, thereby escalating disease transmission. This review is intended to offer an exhaustive overview of the existing mathematical models that have been applied to understand the dynamics of FLA, especially concerning their interactions with bacteria. An extensive literature review was conducted across Google Scholar, PubMed, and Scopus databases to identify mathematical models that describe the dynamics of interactions between FLA and bacteria, as published in peer-reviewed scientific journals. The literature search revealed several FLA-bacteria model systems, including Pseudomonas aeruginosa, Pasteurella multocida, and Legionella spp. Although the published mathematical models account for significant system dynamics such as predator-prey relationships and non-linear growth rates, they generally overlook spatial and temporal heterogeneity in environmental conditions, such as temperature, and population diversity. Future mathematical models will need to incorporate these factors to enhance our understanding of FLA-bacteria dynamics and to provide valuable insights for future risk assessment and disease control measures.

Echocardiographic diagnosis and clinical implications of wide-open tricuspid regurgitation for evaluating right ventricular dysfunction in the emergency department.

The tricuspid regurgitation pressure gradient (TRPG) reflects the difference in pressure between the right ventricle and right atrium (ΔPRV-RA). Its estimation by echocardiography correlates well with that obtained using right-heart catheterization. An elevated TRPG is an important marker for identifying right ventricular dysfunction in both the acute and chronic settings. However, in the "wide-open" variant of TR, the TRPG counterintuitively falls. Failure to recognize this potential pitfall and underlying pathophysiology can cause underestimation of the severity of right ventricular dysfunction. This could lead to erroneous fluid tolerance assessments, and potentially harmful resuscitative and airway management strategies. In this manuscript, we illustrate the pathophysiology and potential pitfall of wide-open TR through a series of cases in which emergency physicians made the diagnosis using cardiac point-of-care ultrasound. To our knowledge, this clinical series is the first to demonstrate recognition of the paradoxically-low TRPG of wide-open TR, which guided appropriate management of critically ill patients in the emergency department.

Point of Care Ultrasound Diagnosis of Maxillary Artery Pseudoaneurysm in the Emergency Department.

A pseudoaneurysm results from a tear in a vessel wall. This leads to extravasation of blood into adjacent tissue and eventual formation of a fibrous sac that maintains continuity with the lumen. These vascular injuries very rarely occur in deeper vessels of the face (e.g. maxillary artery) due to protection from structures like the bony mandible and parotid gland. If left untreated, these pseudoaneurysms can lead to infection, thromboembolism, hemorrhage, and compression of surrounding structures such as facial nerve branches. Pseudoaneurysms are typically diagnosed by advanced imaging techniques including computed tomography angiography and magnetic resonance angiography. However, these tests require time to perform and interpret, are costly, and take place outside the patient care area. Computed tomography also confers ionizing radiation. Fortunately, point of care ultrasound (POCUS) is a readily available, dynamic imaging tool that can be performed at the bedside. Here we present the first known case report of a maxillary artery pseudoaneurysm diagnosed by POCUS in the emergency department. Early differentiation from a typical hematoma led to rapid management in the form of a compression bandage, as well as expedited consultation to the appropriate services.

Unveiling the Chemical Composition, Bioactive Profile and Antioxidant Capacity of Dried Egyptian Jew's Mallow Stems as a Promising Anticancer Agent.

Phytochemicals from waste materials generated by agricultural and industrial processes have become globally significant due to their accessibility and potential effectiveness with few side effects. These compounds have essential implications in both medicine and the economy. Therefore, a quantitative analysis of the phytochemical profile, sugar types, and water-soluble vitamins of dried Corchorus olitorius L."DJMS" extract (dried Jew's mallow stem) was carried out with HPLC. In addition, the chemical composition, TPC, chlorophyll a and b, beta-carotene, and antioxidant effect using DPPH were investigated. Furthermore, the anticancer activity of the DJMS was evaluated by SRB assay using Huh-7 and MDA-MB-231 cell lines. In the quantitative study, DJMS extract showed a high antioxidant potential (67%) due to its content of bioactive compounds such as TPC (276.37 mg 100 g-1) and chlorophyll a and b (20.31, 12.02 mg 100 g-1, respectively), as well as some vitamins and minerals such as B-complex (B12; 146.8 mg 100 g-1 and vitamin C 6.49 mg 100 g-1) and selenium (<0.2 µg kg-1). Moreover, the main sugar types found were sucrose and stachyose, which recorded 9.23 and 6.25 mg 100 g-1, respectively. Identifying phenolic and flavonoids showed that the major components were ellagic acid (4905.26 µg kg-1), ferulic acid (3628.29 µg kg-1), chlorogenic acid (3757.08 µg kg-1), luteolin-7-O-glucoside (4314.48 µg kg-1), naringin (4296.94 µg kg-1) and apigenin-6-rhamnose-8 glucoside (3078.87 µg kg-1). The dried stem extract showed significant MDA-MB-231 inhibition activity and reached 80% at a concentration of 1000 µg/mL of DJMS extract, related to the content of phytochemical components such as isoflavones like genistein (34.96 µg kg-1), which had a tremendous anticancer effect. Hence, the stem of Jew's mallow (which is edible and characterized by its viability and low production cost) possesses the capacity to serve as a pharmaceutical agent for combating cancer owing to its abundance of bioactive components.

Expression profile of serum LncRNAs MALAT-1 and CCAT-1 and their correlation with Mayo severity score in ulcerative colitis patients can diagnose and predict the prognosis of the disease.

Background: Ulcerative colitis (UC) has emerged as an accelerated-incidence chronic condition. UC has been identified as a precancerous lesion for colorectal cancer. Up-to-date genomic research revealed the value of many noncoding RNAs (ncRNAs) in UC pathogenesis, diagnosis, and prognosis. Aim: The present study was aimed at measuring both MALAT-1 and CCAT-1 in the sera of UC patients as diagnostic and prognostic biomarkers and correlating them with the Mayo score which is a novel predictive indicator of malignant transformation as well as with clinicopathological characteristics of the disease. Patients and methods: Sixty-six UC patients and 80 healthy individuals participated in this study, the serum fold changes of MALAT-1 and CCAT-1 were measured by using quantitative real-time PCR (qRT-PCR). Results: The current study findings include overexpressed lncRNAs MALAT-1 and CCAT-1 in the sera of ulcerative colitis patients [(median (IQR) = 2.290 (0.16-9.36), mean ± SD = 3.37 ± 3.904 for MALAT-1, and median (IQR) = 7.305 (0.57-16.96), mean ± SD = 6.81 ± 4.002 for CCAT-1 than controls, ROC curve analysis reported that these genes could predict UC. Both genes were positively correlated with each other which enforces their synergistic effects. Both genes are diagnostic for UC patients.We related studied genes to the severity of the disease. In addition to a significant positive correlation between each gene with ESR and Mayo score, we further classified the patients according to severity (according to Mayo score to remission, mild, moderate, and severe groups) with the following results; lower levels of MALAT-1 and CCAT-1 were significantly associated with mild disease and increased gradually with more severe forms of the disease (p < 0.05). Linear regression analysis with Mayo Score as a dependent variable revealed that only the predictive power of CCAT-1 and ESR are significant. Moreover, ROC curve analysis when compared to that of the Mayo score revealed that CCAT-1 reached 99 % accuracy. In summary, both genes are prognostic factors for UC patients. Conclusion: MALAT-1 and CCAT-1 are diagnostic and prognostic serum biomarkers of ulcerative colitis.

Imperatorin from the aerial parts of Cleome viscosa L.: a characterization study and evaluation of the antibacterial activity.

Cleome viscosa L., a member of the family Cleomaceae, is a potential medicinal plant, known for several bioactive properties such as: anticancer, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, wound healing, etc. Our study aimed to isolate a bioactive compound and assess its antibacterial activity. The crystal compound imperatorin was isolated and reported for the first time from the aerial parts of C. viscosa. The isolation was made using silica gel (100-200 mesh) column chromatography. The structure of imperatorin was investigated through single-crystal XRD, unit cell molecules, FTIR, and ESI-MS spectral analysis. The results validated imperatorin's triclinic crystal structure and P2i/c distance group. The electronic structure was also calculated (4.28/6.21 D) along with the frontier molecular orbital, dipole moment, atomic charges, and electrostatic map of particles in gaseous stage and active site. Imperatorin showed highest activity at 40 µg/mL concentration against Gram + ve bacteria: Staphylococcus aureus (3 ± 0.2 mm), Bacillus subtilis (3 ± 0.6 mm), and Gram -ve bacteria: Klebsiella pneumoniae (3 ± 0.2 mm), Escherichia coli (5 ± 0.2 mm). The study highlights that the compound can be isolated in larger quantities as the plant is easily available across the tropics.

Development of sensitive spectrofluorometric approach based on formation of pyrrolidone derivative for determination of linagliptin through condensation reaction with ninhydrin and phenylacetaldehyde: Application to content uniformity and real plasma.

The new drug linagliptin belongs to the class of dipeptidyl peptidase-4 enzyme inhibitors. Linagliptin is used to treat type 2 diabetes and is taken orally either alone or in combination with other drugs. In this instance, a new, simple, and economical technique for analyzing linagliptin was developed by the effective use of a pyrrolidone derivative. The primary amine group of linagliptin permits its condensation with ninhydrin (0.14% w/v) to produce a fluorescent product in the presence of phenylacetaldehyde (0.02% v/v). All experimental parameters were carefully examined and adjusted in order to monitor the generation of the pyrrolidone derivative at excitation and emission wavelengths of 385 and 475 nm, respectively. The calibration graph was made by plotting the intensity of the fluorescence in relation to linagliptin concentration. A significant linearity was found for values ranging from 20 to 460 ng/mL. The process's validity has been verified by a thorough assessment of the instructions provided by the International Conference on Harmonization (ICH). The results indicate excellent uniformity with a reference method, showing that there is no substantial difference in precision and accuracy. The proposed approach was utilized for determining linagliptin in real rat plasma successfully owing to its high sensitivity. Additionally, the proposed approach was evaluated using the Eco-Scale evaluation tool and showed a high degree of eco-friendliness (86/100).

Evaluated gene expressions of Metallo beta lactamase genes GIM and , VIM, SPM in Pseudomonas aeruginosa clinical isolates.

Pseudomonas aeruginosa is considered as one of the human health care problems, P. aeruginosa's carbapenem resistance emerges by several different mechanisms, some of which include carbapenems genes. P. aeruginosa's carbapenem resistance is a significant health concern, So this study aims to evaluate MBL gene expressions. The study was conducted at the Department of Microbiology, AL-Mahmoodia Hospital, over one year from January to December 2022. The samples were collected from patients with different clinical sources (Burn, Urine, Wound, Sputum, Ear, and Blood), from different ages while. Samples were collected from three hospitals in Baghdad including Al-Yarmouk Teaching Hospital, AL-Mahmmodiya Hospital, and Child's Central Teaching Hospital. A study analyzed 55 P. aeruginosa strains from various clinical sources, the study utilizes the chemical characterization, VITEK 2 system, 16s rRNA, antibiogram sensitivity tests, antibiotic susceptibility using eight antibiotics, including Amikacin, Ciprofloxacin, Levofloxacin, Imipenem Meropenem, Piperacillin, Cefepim and Aztreonam. The test of bacterial susceptibility revealed that each isolate was highly resistant to piperacillin, which are 96.36%, and lower resistance to Ciprofloxacin, which are 32%. Phenotypic screening carbapenem resistance methods combined the disk synergy test and conventional PCR that were used to detect isolates by using 16 S rRNA. This proves that the bacteria is P. aeruginosa and computed by measuring gene expression of the target genes (GIM, VIM, SPM) by using the real-time PCR, which is employed for twenty-five isolates. The result indicates that the expression level of the VIM gene is highly regulated in carbapenem-resistance isolates compared to control isolates that is 1.00. While the expression level of gene GIM and SPM is downregulated in carbapenem-resistance isolates compared to control isolates that is 6. The carbapenem VIM and GIM, SPM (class B) genes are essential for resistance in P. aeruginosa induced by chromosomal changes that modify membrane permeability efflux pump overexpression for genes. As a result, many studies require for discovering new strategies to reduce the threat to public health through preventing the spread of these isolates via tight infections, control measures, and the reduction of the danger to public health.

Red cell distribution width as a prognostic marker for complications of community-acquired pneumonia in children: a comparison with Proadrenomedullin and Copeptin.

BACKGROUND: Community-acquired pneumonia (CAP) is the most common leading cause of morbidity and mortality in children; so, early identification of patients with CAP, who are at risk of complications or high mortality, is very critical to identify patients who need early admission to the intensive care unit. PURPOSE OF THE STUDY: To explore the prognostic value of Red Cell Distribution Width (RDW), Proadrenomedullin and Copeptin in the prediction of complicated CAP in children. METHODS: 99 children were enrolled in the study, which was done at the Pediatric Department of Minia University Hospital. Measurement of serum Proadrenomedullin, Copeptin, and RDW was done to all participating children in the first 24 h of admission. Assessment of the severity of CAP was done using the Pediatric Respiratory Severity Score (PRESS). RESULTS: The values of RDW, Proadrenomedullin, and Copeptin were significantly higher in the complicated CAP group than in the uncomplicated one (P value < 0.01). There were significant positive correlations between RDW and Proadrenomedullin with PRESS (r 0.56 for both). For the prediction of complications, RDW at cutoff point > 17.4, has 77.7% of sensitivity and 98.6% of specificity, followed by Pro ADM at cutoff point > 5.1 nmol/L, of 74% of sensitivity and 90.2% of specificity. For the prediction of mortality, RDW at cutoff point > 17.4 has 81.25% of sensitivity and 89.16% of specificity. CONCLUSION: The RDW is a reliable predictor of poor outcomes in pediatric CAP.

In vitro and In silico assessment of antischistosomal activities of ethanolic extract of Cornulacamonacantha.

Schistosomiasis is the second most prevailing parasitic disease worldwide. Although praziquantel is considered an effective drug in the treatment against schistosomiasis to some extent, there is an emerging drug resistance that widely recorded. Therefore, there is an urgent need to develop effective and safe anti-schistosomal drugs. In this study, Cornulaca monacantha (C. monacantha), a sub-saharan plant, was extracted using aqueous ethanol and characterized by High-Performance Liquid Chromatography (HPLC). Major constituents of the extract are belonging to flavonoids, tannins and phenolic glycosides. Worms' viability and surface morphology of Schistosoma mansoni (S. mansoni) adult worms treated with the extract were assessed using in vitro viability assay, Scanning Electron Microscopy (SEM), and histological examination. The extract (80-350 µg/ml) reduced viability percentage of worms by 40-60% and caused degeneration of both oral and ventral suckers, tegumental, sub-tegumental and muscular damage. Molecular docking approach was utilized to assess the binding affinities of the extracted compounds with S. mansoni alpha-carbonic anhydrase (SmCA), an essential tegument protein. Pharmacokinetic analysis using SwissADME showed that 7 compounds have high drug similarity. This study confirms the in vitro schistomicidal activity of C. monacantha extract against S. mansoni adult worms and suggests potential SmCA inhibition.

Expression profile of LncRNA ANRIL, miR-186, miR-181a, and MTMR-3 in patients with preeclampsia.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Several studies demonstrated the role of lncRNAs and miRNAs in the pathogenesis of preeclampsia; the aim was to detect the expression profiles of serum LncRNA ANRIL, miR-186, miR-181a, and MTMR-3 in patients with preeclampsia. The study included 160 subjects divided into 80 subjects considered as a control group, 80 patients with preeclampsia. We found that there was a significant difference between the preeclampsia and control groups with up-regulation of miR-186 median (IQR) = 4, 29 (1.35-7.73) (P < 0.0001), miR-181a median (IQR) = 2.45 (0.83-6.52) (P = 0.028), and downregulation of lncRNA ANRIL median (IQR) = 0.35(0.28-0.528) (P < 0.0001), MTMR median (IQR) = 0.32(0.155-1.11), (P < 0.0001). ROC curve of lncRNA ANRIL, miR-186, miR-181a, and MTMR-3 in preeclampsia patients showing the roles of these markers in the diagnosis of preeclampsia. In conclusion, serum LncRNA ANRIL, miR-186, miR-181a, and MTMR-3 could be promising biomarkers in the diagnosis of preeclampsia.

Hematological, biochemical, genotoxic, and histopathological changes induced by pyridaben.

The current work examined the genotoxic effects of pyridaben (PDB) in male Sprague Dawley rats. Twenty Sprague Dawley rats were divided into four equal groups; the first group was used as a control group; the other three groups were exposed to 19, 28.5, and 57 mg/kg b.w PDB by oral gavage for 4 weeks. Blood samples were collected for hematological and biochemical parameters; femoral bone marrow was flushed for chromosomal aberrations (CA) assay and liver samples were used for the analysis of gene expression of IL-6 and Casp-3 as well as histopathological and immunhistochemical investigation for Casp-3. The results showed that PDB exposure lead to non-significant changes in hematological parameters in all PDB administrated groups while malondialdehyde, glutathione peroxidase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in 19 and 57 mg/kg PDB doses groups Also, gene expression of IL-6 and Casp-3 revealed a significant increase in 28.5 and 57 mg/kg PDB doses groups as compared with the control. However, there was no significant change in the percentage of CAs in bone marrow cells in all PDB-exposed groups. The histopathological and immunhistochemical examination showed focal areas of inflammatory cellular infiltration with fibrosis in 57 mg/kg b.w PDB dose group accompanied by the severe positive reaction of caspase3 in the liver.

The educational value of ward rounds as a learning and teaching opportunity for house officers, medical officers, and registrars in Sudanese hospitals: a multi-center cross-sectional study.

BACKGROUND: Ward rounds are a cornerstone in the educational experience of junior doctors and an essential part of teaching patient care. Here, we aimed to assess the doctors' perception of ward rounds as an educational opportunity and to identify the obstacles faced in conducting a proper ward round in Sudanese hospitals. METHOD: A cross-sectional study was conducted from the 15th to the 30th of January 2022 among house officers, medical officers, and registrars in about 50 teaching and referral hospitals in Sudan. House officers and medical officers were considered the learners, while specialist registrars were considered the teachers. Doctors' perceptions were assessed using an online questionnaire, with a 5-level Likert scale to answer questions. RESULTS: A total of 2,011 doctors participated in this study (882 house officers, 697 medical officers, and 432 registrars). The participants were aged 26.9 ± 3.2 years, and females constituted about 60% of the sample. An average of 3.1 ± 6.8 ward rounds were conducted per week in our hospitals, with 11.1 ± 20.3 h spent on ward rounds per week. Most doctors agreed that ward rounds are suitable for teaching patient management (91.3%) and diagnostic investigations (89.1%). Almost all the doctors agreed that being interested in teaching (95.1%) and communicating appropriately with the patients (94.7%) make a good teacher in ward rounds. Furthermore, nearly all the doctors agreed that being interested in learning (94.3%) and communicating appropriately with the teacher (94.5%) make a good student on ward rounds. About 92.8% of the doctors stated that the quality of ward rounds could be improved. The most frequently reported obstacles faced during ward rounds were the noise (70%) and lack of privacy (77%) in the ward environment. CONCLUSION: Ward rounds have a special value in teaching patient diagnosis and management. Being interested in teaching/learning and having good communication skills were the two major criteria that make a good teacher/learner. Unfortunately, ward rounds are faced with obstacles related to the ward environment. It is mandatory to ensure the quality of both ward rounds' teaching and environment to optimize the educational value and subsequently improve patient care practice.

Role of Long non Coding RNAs, NEAT1 and Lnc-DC Expression in Pediatric Immune Thrombocytopenic Purpura.

Background: Pediatric immune thrombocytopenic purpura (ITP) is an autoimmune disease; whose etiology is unknown. lncRNAs are regulators of numerous actions, which participate in the development of autoimmune diseases. We evaluated the expression ofNEAT1 and Lnc-RNA in dendritic cell (Lnc-DC) in pediatric ITP. Methods: Sixty ITP patients and 60 healthy subjects were enrolled in the present study; Real-time PCR was performed to assess the expression levels of NEAT1 and Lnc-DC in sera of children with ITP as well as healthy children. Results: Both lncRNAs, NEAT1 and Lnc-DC were significantly upregulated in ITP patients in comparison to controls (p <0.0001 and P= 0.001 respectively). Furthermore, significant upregulation of the expression levels of NEAT1 and Lnc-DC were observed in the non-chronic compared with chronic ITP patients. Also, there was significant negative correlation between each of NEAT1 and Lnc-DC and platelet counts before treatment (r= -0.38; P= 0.003 and r= -0.461; P< 0.0001, respectively). Conclusions: serum lncRNAs, NEAT1 and Lnc-DC could be used as potential biomarkers in differentiating childhood ITP patients and healthy controls in addition to differentiating non-chronic from chronic ITP which may provide a theoretical basis for the mechanism and treatment of immune thrombocytopenia.

Zinc(II) complexation strategy for ultra-sensitive fluorimetric estimation of molnupiravir: Applications and greenness evaluation.

The endemicity of the pandemic coronavirus disease 2019 (COVID-19) infection proved to be transitional only. Spikes are forming again in 2023, and high expectations are returning for reinfections and viral mutations. Molnupiravir (MOL) has been approved as an oral antiviral drug for the treatment of the COVID-19 causative virion. Therefore, the development of an ultrasensitive, instantaneous, and cost-effective method for the quantification of MOL in real plasma samples and formulated dosage form are mandatory. The proposed approach is based on the synthesis of a MOL metal-chelation product. MOL as a ligand was chelated with 1.0 mM zinc(II) in an acetate buffer (pH 5.3). After illumination at 340 nm, the intensity of the MOL fluorescence measured at 386 nm was increased by about 10-fold. The linearity range was found to be from 60.0 to 800.0 ng mL-1 with limit of quantitation (LOQ) of 28.6 ng mL-1 . Two methods were utilized for measuring the greenness of the proposed method (Green Analytical Procedure Index [GAPI] and analytical greenness metric [AGREE] methods), with results equal to 0.8. The binding stoichiometry of MOL with the zinc(II) ion was found to be 2:1. All the experimental parameters were optimized and validated using International Conference on Harmonization (ICH) and United States Food and Drug Administration (US-FDA) recommendations. Furthermore, the fluorescent probes were successfully utilized in real human plasma with high percentages of recovery (95.6%-97.1%) without any matrix interferences. The mechanism of fluorescent complex formation was confirmed using 1 H NMR in the presence and absence of Zn(II). The method was further utilized for testing content uniformity of MOL in its marketed capsule dosage forms.

An Innovative Polymer-Based Electrochemical Sensor Encrusted with Tb Nanoparticles for the Detection of Favipiravir: A Potential Antiviral Drug for the Treatment of COVID-19.

An innovative polymer-based electro-sensor decorated with Tb nanoparticles has been developed for the first time. The fabricated sensor was utilized for trace determination of favipiravir (FAV), a recently US FDA-approved antiviral drug for the treatment of COVID-19. Different techniques, including ultraviolet-visible spectrophotometry (UV-VIS), cyclic voltammetry (CV), scanning electron microscope (SEM), X-ray Diffraction (XRD) and electrochemical impedance spectroscopy (EIS), were applied for the characterization of the developed electrode TbNPs@ poly m-THB/PGE. Various experimental variables, including pH, potential range, polymer concentration, number of cycles, scan rate and deposition time, were optimized. Moreover, different voltammetric parameters were examined and optimized. The presented SWV method showed linearity over the range of 10-150 × 10-9 M with a good correlation coefficient (R = 0.9994), and the detection limit (LOD) reached 3.1 × 10-9 M. The proposed method was applied for the quantification of FAV in tablet dosage forms and in human plasma without any interference from complex matrices, obtaining good % recovery results (98.58-101.93%).

Generation of induced pluripotent stem cell-derived beta-cells in blood amino acids-like medium.

Traditional cell culture media do not accurately represent the availability of the nutrients in plasma. They usually contain a supraphysiological concentration of nutrients such as glucose, amino acids, etc. These high nutrients can alter the metabolism of cultured cells and induce metabolic phenotypes that do not reflect in vivo conditions. We demonstrate that the supraphysiological levels of nutrients interfere with endodermal differentiation. Refinement of media formulations has a potential application in maturity modulation of stem cell-derived ß-cells (SC-ß) generation in vitro. To address these issues, we established a defined culture system to derive SC-ß-cells using a blood amino acids-like medium (BALM). Human induced pluripotent stem cells (hiPSCs) can be efficiently differentiated into the definitive endoderm, pancreatic progenitors, endocrine progenitors, and SC-ß in BALM-based med. The differentiated cells secreted C-peptide in vitro in response to high glucose levels and expressed several pancreatic ß-cell markers. In conclusion, amino acids at the physiological levels are sufficient for deriving functional SC-ß cells.