Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway.

Sedatives promote calmness or sleepiness during surgery or severely stressful events. In addition, depression is a mental health issue that negatively affects emotional well-being. A group of drugs called anti-depressants is used to treat major depressive illnesses. The aim of the present work was to evaluate the effects of quercetin (QUR) and linalool (LIN) on thiopental sodium (TS)-induced sleeping mice and to investigate the combined effects of these compounds using a conventional co-treatment strategy and in silico studies. For this, the TS-induced sleeping mice were monitored to compare the occurrence, latency, and duration of the sleep-in response to QUR (10, 25, 50 mg/kg), LIN (10, 25, 50 mg/kg), and diazepam (DZP, 3 mg/kg, i.p.). Moreover, an in silico investigation was undertaken to assess this study's putative modulatory sedation mechanism. For this, we observed the ability of test and standard medications to interact with various gamma-aminobutyric acid A receptor (GABAA) subunits. Results revealed that QUR and LIN cause dose-dependent antidepressant-like and sedative-like effects in animals, respectively. In addition, QUR-50 mg/kg and LIN-50 mg/kg and/or DZP-3 mg/kg combined were associated with an increased latency period and reduced sleeping times in animals. Results of the in silico studies demonstrated that QUR has better binding interaction with GABAA α3, ß1, and γ2 subunits when compared with DZP, whereas LIN showed moderate affinity with the GABAA receptor. Taken together, the sleep duration of LIN and DZP is opposed by QUR in TS-induced sleeping mice, suggesting that QUR may be responsible for providing sedation-antagonizing effects through the GABAergic interaction pathway.

Current understanding of CTLA-4: from mechanism to autoimmune diseases.

Autoimmune diseases (ADs) are characterized by the production of autoreactive lymphocytes, immune responses to self-antigens, and inflammation in related tissues and organs. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is majorly expressed in activated T cells and works as a critical regulator in the inflammatory response. In this review, we first describe the structure, expression, and how the signaling pathways of CTLA-4 participate in reducing effector T-cell activity and enhancing the immunomodulatory ability of regulatory T (Treg) cells to reduce immune response, maintain immune homeostasis, and maintain autoimmune silence. We then focused on the correlation between CTLA-4 and different ADs and how this molecule regulates the immune activity of the diseases and inhibits the onset, progression, and pathology of various ADs. Finally, we summarized the current progress of CTLA-4 as a therapeutic target for various ADs.

Nutritional and in vitro antioxidant activity analyses of formulated soymilk dessert.

Soymilk (SM) is nutritionally nearly equal to milk from cows and is free of cholesterol, gluten, and lactose. This study's objective was to formulate a cholesterol-free soymilk dessert (SOD) and compare it's to commercial desserts (CODs). Results indicated that the CODs contain substantial amounts of cholesterol while SOD does not. Soymilk dessert has more protein, and vitamin E than CODs, but less fat and calcium. In addition, the result also highlighted that SOD has higher number of amino acids compared to CODs. The total antioxidant, flavonoids and phenolics content of SOD were significantly higher than CODs. Furthermore, the in vitro antioxidant activity of SOD and CODs by DPPH and ABTS methods revealed that the IC50 of SODs significantly (p < 0.001) lower than CODs, and lower IC50 indicated the higher free radical scavenging power of SODs than CODs. These findings indicated that this non-dairy SOD may provide beneficial protein, as well as minerals, and antioxidants to support the body's various physiological functions.

Phylogenetic analysis and characterization of arsenic (As) transforming bacterial marker proteins following isolation of As-tolerant indigenous bacteria.

Marker proteins play a significant role in bacterial arsenic (As) transformation. Phylogenetic analysis and three-dimensional (3D) characteristics of As transforming bacterial marker proteins guide the evolutionary origin and As transforming potential of the species. Indeed, As-tolerant bacteria also show a significant level of As transformation. Hence, characterization of As transforming bacterial marker proteins, isolation of As transforming bacteria, and proper integration of the findings may guide to elucidate how bacteria transform As. Therefore, phylogenetic analysis and 3D characterization of As transforming bacterial marker protein following isolation of potential indigenous As-tolerant indigenous bacteria were done to explore the mechanism of bacterial As transformation. Phylogenetic analysis of ten As transforming marker proteins (arsA, arsB, arsC, arsD, arsR, aioA, arrA, aioB, acr1, and acr3) in 20 potential bacterial genomes (except 19 for the acr3) were studied. Some bacterial genomes featured up to five marker proteins, and therefore, 3D characteristics of the marker proteins were analyzed in those genomes having three-to-five marker proteins. In phylogeny, species in close clades represent their phylogenetic resemblances and may have similar functions. P. aeruginosa, E. coli, and K. pneumonia were found to be more effective due to having the highest number (five) of marker proteins. In 3D protein modeling, most of the marker proteins were found to be active. Among 19 indigenous bacterial isolates, multiple isolates showed tolerance up to 50 mM As(III) and 250 mM As(V), which may potentially transform a significant quantities of As. Hence, integration of the results of phylogenetic analysis, 3D protein characteristics, and As tolerance in the bacterial isolates could guide to explore the mechanism of how bacteria transform As at cellular and molecular levels.

Nutritional, Phytochemical, and In Vitro Antioxidant Activity Analysis of Different States of Soy Products.

Consumer demand for food nutritional content and quality is driving the design of plant-based foods that are enhanced with proteins. In this study, we aimed to reveal the nutrient compositional differences of various states of soy flours. We compared soy protein concentrate (SPC) with full fat (FF), raw soy flour (RSF), and defatted (DF) soy flour for investigating nutritional content, phytochemicals, and in vitro antioxidant activity. The results showed that the SPC contained significantly (p < 0.001) higher protein content (65.14%) and low-fat content (0.54%) than RSF, FF, and DF. Furthermore, the findings revealed that all products contain a significant (ANOVA, p < 0.001) amount of essential minerals. The RSF contains significantly higher (p < 0.001) potassium (1178.6 mg), calcium (216.77 mg), and magnesium (247 mg) per 100 g than FF, DF, and SPC. SPC contains essential amino acids, but we were unable to detect phenylalanine and tryptophan due to a limitation in the method. Furthermore, using methanolic and aqueous extracts of RSF, FF, DF, and SPC, the flavonoid, phenolics, and antioxidant capacity were also evaluated. According to the findings, soy products in methanolic extract had higher phenolic (about 12-34 mg/g) and flavonoid (about 63-150 mg/g) levels than aqueous extract. Results also demonstrated that FF had higher phenolic content, and SPC had higher flavonoid content than the other products. In vitro models such as phosphomolybdenum blue, FRAP, DPPH, and ABTS assays were used to study the total antioxidant and free radical scavenging potential of soy products, and results found that soy products contained a significant (p < 0.001) amount of antioxidant equivalent to gallic acid and vitamin C standard. In the DPPH and ABTS assays, the results also showed that soy products can reduce free radicals in different in vitro models. Altogether, these findings suggest that soy flours, particularly DF and SPC, could be a beneficial food ingredient in the formulation of functional foods.

In silico functional and pathway analysis of risk genes and SNPs for type 2 diabetes in Asian population.

Type 2 diabetes (T2D) has earned widespread recognition as a primary cause of death, disability, and increasing healthcare costs. There is compelling evidence that hereditary factors contribute to the development of T2D. Clinical trials in T2D have mostly focused on genes and single nucleotide polymorphisms (SNPs) in protein-coding areas. Recently, it was revealed that SNPs located in noncoding areas also play a significant impact on disease vulnerability. It is required for cell type-specific gene expression. However, the precise mechanism by which T2D risk genes and SNPs work remains unknown. We integrated risk genes and SNPs from genome-wide association studies (GWASs) and performed comprehensive bioinformatics analyses to further investigate the functional significance of these genes and SNPs. We identified four intriguing transcription factors (TFs) associated with T2D. The analysis revealed that the SNPs are engaged in chromatin interaction regulation and/or may have an effect on TF binding affinity. The Gene Ontology (GO) study revealed high enrichment in a number of well-characterized signaling pathways and regulatory processes, including the STAT3 and JAK signaling pathways, which are both involved in T2D metabolism. Additionally, a detailed KEGG pathway analysis identified two major T2D genes and their prospective therapeutic targets. Our findings underscored the potential functional significance of T2D risk genes and SNPs, which may provide unique insights into the disease's pathophysiology.

Genome-Wide Identification and Functional Analysis of Lysine Histidine Transporter (LHT) Gene Families in Maize.

Amino acid transporters (AATs) are essential membrane proteins that transfer amino acids across cells. They are necessary for plant growth and development. The lysine histidine transporter (LHT) gene family in maize (Zea mays) has not yet been characterized. According to sequence composition and phylogenetic placement, this study found 15 LHT genes in the maize genome. The ZmLHT genes are scattered across the plasma membrane. The study also analyzed the evolutionary relationships, gene structures, conserved motifs, 3D protein structure, a transmembrane domain, and gene expression of the 15 LHT genes in maize. Comprehensive analyses of ZmLHT gene expression profiles revealed distinct expression patterns in maize LHT genes in various tissues. This study's extensive data will serve as a foundation for future ZmLHT gene family research. This study might make easier to understand how LHT genes work in maize and other crops.

Thymoquinone against infectious diseases: Perspectives in recent pandemics and future therapeutics.

The recent pandemics caused by coronavirus infections have become major challenges in 21st century human health. Scientists are struggling hard to develop a complete cure for infectious diseases, for example, drugs or vaccines against these deadly infectious diseases. We have searched papers on thymoquinone (TQ) and its effects on different infectious diseases in databases like Pubmed, Web of Science, Scopus, and Google Scholar, and reviewed them in this study. To date research suggests that natural products may become a potential therapeutic option for their prodigious anti-viral or anti-microbial effects on infectious diseases. TQ, a natural phytochemical from black seeds, is known for its health-beneficial activities against several diseases, including infections. It is evident from different in vitro and in vivo studies that TQ is effective against tuberculosis, influenza, dengue, Ebola, Zika, hepatitis, malaria, HIV, and even recent pandemics caused by severe acute respiratory syndrome of coronaviruses (SARS-CoV and SARS-CoV-2). In these cases, the molecular mechanism of TQ is partly clear but mostly obscure. In this review article, we have discussed the role of TQ against different infectious diseases, including COVID-19, and also critically reviewed the future use of TQ use to fight against infectious diseases.

Mental health difficulties of adults with COVID-19-like symptoms in Bangladesh: A cross-sectional correlational study.

BACKGROUND: The rapid spread of novel corona virus disease (COVID-19) coupled with inefficient testing capacities in Bangladesh has resulted in a number of deaths from COVID-19-like symptoms that have no official test results. This study was the first study that explored the mental health of adults with the most common COVID-19-like symptoms in Bangladesh. METHODS: This cross-sectional correlational study gathered data via an online survey to explore the mental health of Bangladeshi adults with symptoms akin to COVID-19. Level of stress, anxiety symptoms, and depressive symptoms were measured with the DASS-21. Chi-square tests and multivariate logistic regression was performed to examine the association of variables. RESULTS: The prevalence rates of anxiety symptoms and depressive symptoms of the overall population were 26.9% and 52.0% respectively and 55.6% reported mild to extremely severe levels of stress. Multivariate logistic regression determined that respondents with COVID-19-like symptoms reported higher odds for stress level (AOR = 2.043, CI = 1.51 to 2.76), anxiety symptoms (AOR = 2.770, CI = 2.04 to 3.77) and depressive symptoms (AOR = 1.482, CI = 1.12 to 1.96) than asymptomatic respondents. LIMITATIONS: There was a chance of recall bias as it was not possible to validate the information due to the retrospective design of the study. Recruitment methods only captured internet users, which reduces the generalizability of findings. CONCLUSIONS: Patients with symptoms like those of COVID-19 should be prioritized in the healthcare setting in order to reduce mental health difficulties throughout the pandemic .

Current Landscape of Natural Products against Coronaviruses: Perspectives in COVID-19 Treatment and Anti-viral Mechanism.

BACKGROUND: SARS-CoV-2 is a coronavirus, and the infection by SARS-CoV-2, termed as COVID-19, was first reported in Wuhan, China, at the end of 2019, and this outbreak became a pandemic in February of 2020. Till now, there is no effective drug or vaccine against this virus that can make a complete cure; however, a number of drugs are in trials. OBJECTIVES: In this review, we have focused on an alternative therapeutic approach using natural products utilizing the host anti-viral responses for resolving COVID-19 pathogenesis. METHODS: We have searched databases like PubMed, Scopus, Web of Science, and Google Scholar for articles related to natural products and viral diseases, with a specific focus on coronaviruses, as well as other RNA viruses and recent updates on the COVID-19 pandemic, and collected articles and reviewed them comprehensively. RESULTS: Scientific studies clarified the viral pathogenesis that involved viral entrance into host cells and anti-viral response inside the cells, which can be effectively targeted by numerous natural compounds from different sources. Many of these compounds can potentially target viral genomic material or protein machinery. Natural products that were found effective against other coronaviruses, especially SARS-CoV or MERS-CoV (which emerged in 2002 and 2012, respectively), might be effective against SARS-CoV-2 due to their structural similarities. CONCLUSION: COVID-19 pandemic is a global emergency thus, urgent drug development is necessary. Natural products can be the biggest source of drugs, as they have been found to be effective in other coronaviruses previously; however, time is required to establish the clinical success of these drugs for clinical applications.

Optimized Plasmid Construction Strategy for Cas9.

BACKGROUND/AIMS: The target genome editing technology not only plays an important role in basic biology studies but also holds a great promise for potential clinical applications. The new generation of engineered nuclease RGEN (RNA Guided EndoNuclease) is much easier to construct and modify, and attracts more attentions. In the current study, we compared different plasmid construction strategies of Cas9-gRNA (guide RNA). METHODS: Different plasmid construction strategies of Cas9-gRNA were compared. And more modifications were introduced into the plasmid construction strategy. RESULTS: The plasmid construction efficiency of expressing the gRNA and Cas9 in one plasmid was lower than expressing them in two separate plasmids. However, they showed the similar genome editing efficiency. We further introduced the Golden-gate assembly and blue-white screening approaches into the Cas9-gRNA construction procedures, without the process of vector digestion and gel purification. CONCLUSIONS: Combing with the optimized gRNA structure (gRNA-BL) we identified before, we established one more cost-effective, time-saving and efficient plasmid construction strategy for Cas9-gRNA.