Biodiesel synthesis from chicken feather meal using S/AlMCM-41 catalyst and engine performance analysis.

In this study, Sulphated/AlMCM-41 (S/AlMCM-41) catalysts were synthesized and used to produce biodiesel from CFMO. Different percentages of S/AlMCM-41 catalysts were prepared and characterized by X-ray diffraction, BET studies, TPD, and SEM-EDS analysis. Sulphur incorporation to the MCM framework though reduced the surface area, and pore volume of the catalyst, sufficient acidity were produced in the catalyst surface. The existence of functional groups and the composition of the biodiesel obtained was analysed by FTIR and GC-MS. S/AlMCM-41 (80%) catalyst presented a high catalytic activity with maximum biodiesel conversion % when compared to other variants. The bio-ester produced from CFMO with S/AlMCM-41 (80%) catalyst possessed the higher calorific value of 50 MJ/kg and flashpoint of 153 °C and other properties analogous to the standard biodiesel. The engine performance was examined for biodiesel blends with neat diesel, where biodiesel blends performed better than neat diesel. The exhaust gas emission studies also highlighted that the obtained biodiesel showed emission characteristics similar to the standard biodiesel, whereas marginally higher emission for CO and CO2 of about 2.2 and 7.9% was reported.

Therapeutic drug monitoring of vancomycin in surgical patients using a validated HPLC method.

BACKGROUND: Vancomycin is being used for the treatment of a variety of infections caused by methicillin resistant Staphylococcus aureus and methicillin susceptible Staphylococcus aureus. Therapeutic drug monitoring (TDM) is highly recommended for ensuring the safe and effective therapy with vancomycin. A reliable and cost-effective bioanalytical method is required for TDM as well as pharmacokinetic studies of vancomycin. MATERIALS AND METHODS: A selective, sensitive, and cost effective HPLC method was developed and validated for quantification of vancomycin concentrations in human plasma. The mobile phase was a mixture of buffer (50 mM ammonium dihydrogen phosphate, pH 2.4) and acetonitrile 88 : 12 v/v. The separation was carried on C18 column (125 × 4.6 mm, particle size 5 µm) with isocratic flow rate of 0.370 mL/min at room temperature with UV detection at 215 nm. The method was validated for sensitivity, accuracy, and precision as well as stability of vancomycin in human plasma by following European Medicine Agency (EMA) guideline. Therapeutic drug monitoring of vancomycin was performed by quantifying the trough concentrations of vancomycin in 65 human plasma samples after administration of therapeutically relevant dose. RESULTS: The developed method was sensitive enough to quantify vancomycin concentrations as low as 0.25 mg/L in human plasma. Moreover, the method was proved accurate and precise in terms of quantifying the unknown concentration of vancomycin. The evaluation of short-term, long-term, and freeze-thaw stability proved the stability of vancomycin in human plasma. The TDM of vancomycin by using this method showed that 39 (60%) samples were within the target trough concentration range (TTCR), i.e. 10 - 20 mg/L, while 23 samples (35.4%) were below the TTCR, and 3 samples (4.6%) were above this range. CONCLUSION: The developed method is sensitive and cost effective for quantification of vancomycin in human plasma. The results of sample analysis shows that the developed method can be used reliably for TDM of vancomycin.

Preparation and comparison of binary and ternary inclusion complexes of aripiprazole using L-arginine/lysine and MßCD/HPßCD by using different molar ratios.

Aripiprazole (ARI), an antipsychotic having low solubility and stability. To overcome this, formation of binary and ternary using inclusion complexes of Methyl-ß-cyclodextrin (MßCD) /Hydroxy propyl beta cyclodextrin (HPßCD) and L-Arginine (ARG)/ Lysine (LYS) are analyzed by dissolution testing and phase stability study along with their complexation efficacy and solubility constants made by physical mixing. Inclusion complexes with ARG were better than LYS and prepared by solvent evaporation and lyophilization method as well. They are characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (AT-FTIR), X-ray powder diffractometry (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM) and Thermal gravimetric analysis (TGA). The bond shifting in AT-FTIR confirmed the molecular interactions between host and guest molecules. The SEM images also confirmed a complete change of drug morphology in case of ternary inclusion complexes prepared by lyophilization method for both the polymers. ARI: MßCD: ARG when used in the specific molar ratio of 1:1:0.27 by prepared by lyophilization method has 18 times best solubility while ARI:HPßCD:ARG was 7 times best solubility than pure drug making MßCD a better choice than HPßCD. Change in the molar ratio will cause loss of stability or solubility. Solvent evaporation gave significant level of solubility but less stability.

Biochar supported nano core-shell (TiO2/CoFe2O4) for wastewater treatment.

The porous structure of biochar, its large surface area, and its anti-oxidant properties are extensively used for pollutant removal strategies. The literature to date has reported that the biochar assisted metal-oxide core-shells have a dominating degradation ability under solar irradiation. Therefore, this study is significantly focused on cinnamon biochar as an active anti-oxidant agent incorporated in titania-cobalt ferrite nanocore-shell (Biochar/TiO2/CoFe2O4) structures for the first time in wastewater treatment against chlorophenol pollutants. Pure materials, core-shells, and biochar aided composites were synthesized by chemical methods, and their characteristics were analyzed using various instrumentation techniques. The diffraction outcomes of Biochar/TiO2/CoFe2O4 showed the mixed phases containing biochar, TiO2, and CoFe2O4. The morphological characteristics revealed that the biochar creates porosity and a peripheral layer covering the core-shell. Meanwhile, absorption studies of TiO2/CoFe2O4 core-shell and Biochar/TiO2/CoFe2O4 samples achieved 65% and 92% degradation efficiencies when exposed to visible light against chlorophenol pollutants, respectively. All these results confirm the presence of distinct functional groups as well as the combined synergistic effects that activated the charge separation, resulting in the successful destruction of water pollutants. In addition, the highly efficient Biochar/TiO2/CoFe2O4 sample was recycled, and the efficiency was maintained stable for five repeated degradation processes. Thus, Biochar/TiO2/CoFe2O4 will be utilized to expand the possibilities for biofuel generation and energy storage devices.

The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain.

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.

Zinc associated nanomaterials and their intervention in emerging respiratory viruses: Journey to the field of biomedicine and biomaterials.

Respiratory viruses represent a severe public health risk worldwide, and the research contribution to tackle the current pandemic caused by the SARS-CoV-2 is one of the main targets among the scientific community. In this regard, experts from different fields have gathered to confront this catastrophic pandemic. This review illustrates how nanotechnology intervention could be valuable in solving this difficult situation, and the state of the art of Zn-based nanostructures are discussed in detail. For virus detection, learning from the experience of other respiratory viruses such as influenza, the potential use of Zn nanomaterials as suitable sensing platforms to recognize the S1 spike protein in SARS-CoV-2 are shown. Furthermore, a discussion about the antiviral mechanisms reported for ZnO nanostructures is included, which can help develop surface disinfectants and protective coatings. At the same time, the properties of Zn-based materials as supplements for reducing viral activity and the recovery of infected patients are illustrated. Within the scope of noble adjuvants to improve the immune response, the ZnO NPs properties as immunomodulators are explained, and potential prototypes of nanoengineered particles with metallic cations (like Zn2+) are suggested. Therefore, using Zn-associated nanomaterials from detection to disinfection, supplementation, and immunomodulation opens a wide area of opportunities to combat these emerging respiratory viruses. Finally, the attractive properties of these nanomaterials can be extrapolated to new clinical challenges.

Combining RSPH9 founder mutation screening and next-generation sequencing analysis is efficient for primary ciliary dyskinesia diagnosis in Saudi patients.

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy. Dysfunction of motile respiratory and nodal cilia results in sinopulmonary symptoms associated with laterality defects (LD) found in half of the patients. The molecular basis of the disease is insufficiently investigated in patients originating from the Arabian Peninsula. In a group of 16 unrelated Saudi patients clinically suspected of PCD and among whom only 5 (31%) had LD, we first screened by PCR-RFLP two founder mutations, RSPH9 c.804_806del and CCDC39 c.2190del previously identified in patients from the Arabian Peninsula and Tunisia, respectively. When negative, targeted panel or whole-exome sequencing was performed. Three patients were homozygous for the mutation in RSPH9, which encodes an axonemal protein that is absent from nodal cilia. None of the patients carried the CCDC39 founder mutation frequent in Tunisia. NGS analysis showed that nine patients had homozygous mutations in PCD genes. In total, sequential RFLP and NGS analysis solved 75% (12/16) of cases and identified ten distinct mutations, among which six are novel, in nine different genes. These results, which highlight the genetic heterogeneity of PCD in Saudi Arabia, show that the RSPH9 c.804_806del mutation is a prevalent mutation among Saudi patients, whereas the CCDC39 c.2190del ancestral allele is most likely related to the Berber population. This study shows that RSPH9 founder mutation first-line screening and NGS analysis is efficient for the genetic exploration of PCD in Saudi patients. The RSPH9 founder mutation accounts for the low rate of LD among Saudi patients.

Nanohybrid catalysts with porous structures for environmental remediation through photocatalytic degradation of emerging pollutants.

Water supplies have been seriously challenged by new emerging pollutants, which are difficult to remove by traditional wastewater treatment. Thus, new technologies such as catalytic advanced oxidation processes have merged as suitable solutions; however, the drawbacks of typical catalysts limit their application. To overcome this issue, new materials with enhanced textural properties have been developed, showing that their porosity and chemical nature influence their potential as a catalyst. Herein, the recent progress in highly porous catalysts and their suitable deployment to effectively nano-remediate the polluted environmental matrices are reviewed in detail. First, following a brief introduction, several environmental pollutants of emerging concerns from different sectors, including pharmaceutical residues, endocrine-disrupting chemicals (EDCs), pesticides, and hazardous dyes are also introduced with relevant examples. To effectively tackle the sustainable remediation of emerging pollutants, this work also focuses on the multifunctional features of nanohybrid porous materials that act as catalysts constructs to degrade emerging pollutants. The influence of surface reactive centers, stability, bandgap energies, light absorption capacities, and pollutants adsorption capacities are also discussed. Successful examples of the employment of nanohybrid porous catalysts for the degradation of pharmaceutical pollutants, EDCs, pesticides, and hazardous dyes are summarized. Finally, some challenges faced by nanohybrid porous materials to achieve their potential application as advanced catalysts for environmental remediation have been identified and presented herein.

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases.

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.

The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase(Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.

Antidepressant Effect of Crocin in Mice with Chronic Mild Stress.

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain's MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.

Spectroscopic and Molecular Docking Studies of Cu(II), Ni(II), Co(II), and Mn(II) Complexes with Anticonvulsant Therapeutic Agent Gabapentin.

New Cu(II), Ni(II), Co(II), and Mn(II) complexes of the gabapentin (Gpn) bidentate drug ligand were synthesized and studied using elemental analyses, melting temperatures, molar conductivity, UV-Vis, magnetic measurements, FTIR, and surface morphology (scanning (SEM) and transmission (TEM) electron microscopes).The gabapentin ligand was shown to form monobasic metal:ligand (1:1) stoichiometry complexes with the metal ions Cu(II), Ni(II), Co(II), and Mn(II). Molar conductance measurements in dimethyl-sulfoxide solvent with a concentration of 10-3 M correlated to a non-electrolytic character for all of the produced complexes. A deformed octahedral environment was proposed for all metal complexes. Through the nitrogen atom of the -NH2 group and the oxygen atom of the carboxylate group, the Gpn drug chelated as a bidentate ligand toward the Mn2+, Co2+, Ni2+, and Cu2+ metal ions. This coordination behavior was validated by spectroscopic, magnetic, and electronic spectra using the formulas of the [M(Gpn)(H2O)3(Cl)]·nH2O complexes (where n = 2-6).Transmission electron microscopy was used to examine the nanostructure of the produced gabapentin complexes. Molecular docking was utilized to investigate the comparative interaction between the Gpn drug and its four metal [Cu(II), Ni(II), Co(II), and Mn(II)] complexes as ligands using serotonin (6BQH) and dopamine (6CM4) receptors. AutoDock Vina results were further refined through molecular dynamics simulation, and molecular processes for receptor-ligand interactions were also studied. The B3LYP level of theory and LanL2DZ basis set was used for DFT (density functional theory) studies. The optimized geometries, along with the MEP map and HOMO → LUMO of the metal complexes, were studied.

Immunomodulatory Efficacy-Mediated Anti-HCV and Anti-HBV Potential of Kefir Grains; Unveiling the In Vitro Antibacterial, Antifungal, and Wound Healing Activities.

The utilization of fermented foods with health-promoting properties is becoming more popular around the world. Consequently, kefir, a fermented milk beverage made from kefir grains, was shown in numerous studies to be a probiotic product providing significant health benefits. Herein, we assessed the antibacterial and antifungal potential of kefir against a variety of pathogenic bacteria and fungi. This study also showed the effectiveness of kefir in healing wounds in human gastric epithelial cells (GES-1) by (80.78%) compared with control (55.75%) within 48 h. The quantitative polymerase chain reaction (qPCR) results of kefir-treated HCV- or HBV- infected cells found that 200 µg/mL of kefir can eliminate 92.36% of HCV and 75.71% of HBV relative to the untreated infected cells, whereas 800 µg/mL (the highest concentration) completely eradicated HCV and HBV. Moreover, the estimated IC50 values of kefir, at which HCV and HBV were eradicated by 50%, were 63.84 ± 5.81 µg/mL and 224.02 ± 14.36 µg/mL, correspondingly. Kefir can significantly suppress the elevation of TNF-α and upregulate IL-10 and INF-γ in both treated HCV- and HBV-infected cells. High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analysis of kefir revealed the presence of numerous active metabolites which mainly contribute to the antimicrobial, antiviral, and immunomodulatory activities. This study demonstrated, for the first time, the anti-HBV efficacy of kefir while also illustrating the immunomodulatory impact in the treated HBV-infected cells. Accordingly, kefir represents a potent antiviral agent against both viral hepatitis C and B, as well as having antimicrobial and wound healing potential.

Multispectral and Molecular Docking Studies Reveal Potential Effectiveness of Antidepressant Fluoxetine by Forming π-Acceptor Complexes.

Poor mood, lack of pleasure, reduced focus, remorse, unpleasant thoughts, and sleep difficulties are all symptoms of depression. The only approved treatment for children and adolescents with major depressive disorder (MDD) is fluoxetine hydrochloride (FXN), a serotonin selective reuptake inhibitor antidepressant. MDD is the most common cause of disability worldwide. In the present research, picric acid (PA); dinitrobenzene; p-nitro benzoic acid; 2,6-dichloroquinone-4-chloroimide; 2,6-dibromoquinone-4-chloroimide; and 7,7',8,8'-tetracyanoquinodimethane were used to make 1:1 FXN charge-transfer compounds in solid and liquid forms. The isolated complexes were then characterized by elemental analysis, conductivity, infrared, Raman, and 1H-NMR spectra, thermogravimetric analysis, scanning electron microscopy, and X-ray powder diffraction. Additionally, a molecular docking investigation was conducted on the donor moiety using FXN alone and the resulting charge transfer complex [(FXN)(PA)] as an acceptor to examine the interactions against two protein receptors (serotonin or dopamine). Interestingly, the [(FXN)(PA)] complex binds to both serotonin and dopamine more effectively than the FXN drug alone. Furthermore, [(FXN)(PA)]-serotonin had a greater binding energy than [FXN]-serotonin. Theoretical data were also generated by density functional theory simulations, which aided the molecular geometry investigation and could be beneficial to researchers in the future.

Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge-Transfer Complexes.

The charge transfer interactions between the seproxetine (SRX) donor and π-electron acceptors [picric acid (PA), dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), and 7,7',8,8'-tetracyanoquinodi methane (TCNQ)] were studied in a liquid medium, and the solid form was isolated and characterized. The spectrophotometric analysis confirmed that the charge-transfer interactions between the electrons of the donor and acceptors were 1:1 (SRX: π-acceptor). To study the comparative interactions between SRX and the other π-electron acceptors, molecular docking calculations were performed between SRX and the charge transfer (CT) complexes against three receptors (serotonin, dopamine, and TrkB kinase receptor). According to molecular docking, the CT complex [(SRX)(TCNQ)] binds with all three receptors more efficiently than SRX alone, and [(SRX)(TCNQ)]-dopamine (CTcD) has the highest binding energy value. The results of AutoDock Vina revealed that the molecular dynamics simulation of the 100 ns run revealed that both the SRX-dopamine and CTcD complexes had a stable conformation; however, the CTcD complex was more stable. The optimized structure of the CT complexes was obtained using density functional theory (B-3LYP/6-311G++) and was compared.

Enhancement of Haloperidol Binding Affinity to Dopamine Receptor via Forming a Charge-Transfer Complex with Picric Acid and 7,7,8,8-Tetracyanoquinodimethane for Improvement of the Antipsychotic Efficacy.

Haloperidol (HPL) is a typical antipsychotic drug used to treat acute psychotic conditions, delirium, and schizophrenia. Solid charge transfer (CT) products of HPL with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have not been reported till date. Therefore, we conducted this study to investigate the donor-acceptor CT interactions between HPL (donor) and TCNQ and PA (π-acceptors) in liquid and solid states. The complete spectroscopic and analytical analyses deduced that the stoichiometry of these synthesized complexes was 1:1 molar ratio. Molecular docking calculations were performed for HPL as a donor and the resulting CT complexes with TCNQ and PA as acceptors with two protein receptors, serotonin and dopamine, to study the comparative interactions among them, as they are important neurotransmitters that play a large role in mental health. A molecular dynamics simulation was ran for 100 ns with the output from AutoDock Vina to refine docking results and better examine the molecular processes of receptor-ligand interactions. When compared to the reactant donor, the CT complex [(HPL)(TCNQ)] interacted with serotonin and dopamine more efficiently than HPL only. CT complex [(HPL)(TCNQ)] with dopamine (CTtD) showed the greatest binding energy value among all. Additionally, CTtD complex established more a stable interaction with dopamine than HPL-dopamine.

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels.

Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.

Association between interferon-gamma (IFN-γ) gene polymorphisms (+874A/T and +2109A/G), and susceptibility to hepatitis B viral infection (HBV).

BACKGROUND: Interferon-gamma (IFN-γ) is a chief proinflammatory cytokine with a significant role in the immune response against viral infections. Today there is increasing evidence about the association between individual genetic polymorphisms and cytokines in predicting HBV infection susceptibility. AIM: This study aimed to investigate the association between IFN-γ gene polymorphisms and susceptibility to hepatitis B viral infection (HBV), and the impact of these genetic polymorphisms on IFN-γ production. IFN-γ (+874A/T, rs2430561, and +2109A/G, rs1861494) was genotyped by single-stranded polymorphism-polymerase chain reaction (SSP-PCR) in 126 Egyptians with chronic HBV infection and in 100 healthy control subjects. The plasma levels of IFN-γ were measured by Enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to the control subjects there was a slight increase in +874TT genotype frequency in HBV patients. However, no statistical significance in IFN-γ (+874A/T and +2109A/G) genotype/allele distribution was demonstrated, indicating the lack of association between these SNPs and susceptibility to HBV infection. In +2109A/G, only AG genotype was observed with a complete abrogation of GG and AA genotypes. Haplotypes between different loci on selected genes showed insignificant changes in their frequency in patients and control subjects. HBV patients had a significantly higher level of IFN-γ (P < 0.001) compared to controls. The maximum significant increase in IFN-γ production was observed in subjects harboring the +874TA genotype. CONCLUSIONS: As no association could be characterized between the polymorphism in IFN-γ (+874A/T and +2109A/G) and susceptibility to chronic HBV infection, our data support the concept that IFN-γ gene polymorphisms are not predictors of HBV susceptibility in this segment of the Egyptian population.

Insight into the Advances in Clinical Trials of SARS-CoV-2 Vaccines.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has thrown a challenge to the scientific community. Several interventions to stop or limit the spread of infection have failed, and every time the virus emerges, it becomes more contagious and more deadly. Vaccinating a significant proportion of the population is one of the established methods to achieve herd immunity. More than 100 COVID-19 vaccines have been designed and tested against the virus. The development of a new vaccine takes years of testing, but due to the pandemic, healthcare authorities have given emergency use authorization for a few vaccines. Among them are BioNTech and Moderna vaccines (mRNA based); ChAdOx1, Gam-COVID-Vac, Janssen vaccines (vector-based); CoronaVac, COVAXIN (virus inactivated); and EpiVacCorona vaccine (viral peptide). Mixtures of vaccines are also being tested to evaluate their efficacy against mutant strains of SARS-CoV-2. All these vaccines in clinical trials have shown robust production of neutralizing antibodies sufficient to prevent infection. Some of the vaccinated people reported serious complications. However, no definitive relationship could be established between vaccination administration and the occurrence of these complications. None of the COVID-19 vaccines approved to date have been found to be effective against all of the SARS-CoV-2 variants.

Impacts of n-acetyl cysteine on gibberellic acid-induced testicular dysfunction through regulation of inflammatory cytokines, steroid and antioxidant activity.

In agriculture, gibberellic acid (GA3) is commonly used with extreme dangers for public health. The current research evaluates the improving effects of n-acetyl cysteine (NAC, 150 mg/kg bw) co-administered with GA3 (55 mg/kg bw) mediated testicular injury. Twenty-four male albino rats were split into 4 groups: Negative control (CNT), NAC group, positive GA3 group and protective group, co-administered NAC plus GA3. On day 21, rats were anesthetised then euthanised by decapitation. Blood samples were collected; testicular samples were taken for semen analysis, serum chemistry, RNA extraction, histological and antioxidants markers examination. Our results revealed a significant decline p < .05 of catalase level and total antioxidant capacity. There was a substantial rise of MDA concentration in GA3-treated rats along with a considerable decrease of the antioxidant markers (SOD, GSH) and serum male reproductive hormones. In GA3-treated rats, an overexpression of the inflammatory cytokines (TNF-α, IL-1ß) and anti-inflammatory cytokine IL-10 with boost mRNA expression of nuclear factor-kappa (NFk B) were confirmed. There was downregulation of steroidogenesis genes and decrease in sperm quality and concentration with an increase in sperm abnormalities, all were reported in GA3-treated rats. NAC treatment significantly increased the antioxidant state, testicular function beside structural germ cell and seminiferous tubules histology accompanied by upsurge of steroidogenic mRNA expressions (P450scc and 3ß-HSD) and downregulated the pro-inflammatory cytokines mRNA expression (TNF-α, IL-1ß). These results confirm the antioxidant capability of NAC and afford robust evidence about the ameliorative effect of the NAC to attenuate the testicular injury induced by GA3 through modulation of the antioxidant defence system, steroidogenic and pro-inflammatory cytokines mRNA expression.