Carum carvi Modulates Acetaminophen-Induced Hepatotoxicity: Effects on TNF-α, NF-κB, and Caspases

Carum carvi is a well-known herb traditionally used as a spice in Asian countries. Acetaminophen is a known marketed drug mainly used as an analgesic. It has been scientifically proven that consumption of acetaminophen (paracetamol) is associated with liver toxicity if taken in high doses without medical supervision. The present study evaluated the in vivo antioxidant and hepatoprotective efficacy of Carum carvi against acetaminophen-induced hepatotoxicity in Wistar rats. Our results demonstrate that Carum carvi, at doses (mg/kg) of 100 (D1) and 200 (D2), showed inhibitory properties for DNA-sugar damage, lipid peroxidation, DPPH scavenging, and increased reducing potential in a concentration-dependent manner. Our results also confirm that liver toxicity associated with paracetamol, such as depletion of reduced glutathione and antioxidant enzyme levels, as well as induction of cytochrome P450, oxidative stress, apoptosis, and inflammatory cytokines, was efficiently restored by Carum carvi treatment in rats. Moreover, the expression of redox-sensitive transcription factors, namely, NF-κB and TNF-α levels, was also modulated by Carum carvi in the rats. In summary, our study confirms that Carum carvi inhibits inflammation and oxidative stress, thereby protecting liver cells from paracetamol prompted hepatotoxicity

Scenario and future prospects of microRNAs in gastric cancer: A review

Carcinoma of the stomach is one of the major prevalent and principal causes of cancer-related deaths worldwide. Current advancement in technology has improved the understanding of the pathogenesis and pathology of gastric cancers (GC). But, high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate novel early diagnostic/prognostic markers and therapeutic targets for GC, which are sufficiently sensitive to GC. Current biomedical investigations have explored several budding GC biomarker by utilizing serum proteins, natural oncogenic genes during improvement in molecular technologies as microarray, and RNA/DNA-Seq. Recently, small non-coding microRNAs (miRNAs) are becoming vital regulators in oncogenesis pathways and can act as handy clinical biomarkers. The newly introduced class of biomarkers is rising as new molecules for cancer diagnosis and prognosis. For better understanding of the gastric carcinogenesis, miRNAs may help to elucidate the mechanisms of tumor growth and can help to discover novel untimely potent markers for early detection of GC. Here in this review, we summarize the recent research studies supporting the utility of miRNAs as novel early diagnostic/prognostic tools and therapeutic targets. Thus, here we introduce potential future treatment strategies for gastrointestinal (GI) cancers, which indicate the practicality and clinical applications of miRNAs in GC

Box–Behnken Response Surface Design of Polysaccharide Extraction from Rhododendron arboreum and the Evaluation of Its Antioxidant Potential

© 2020 by the authors. In the present investigation, the ultrasound-assisted extraction (UAE) conditions and optimization of Rhododendron arboreum polysaccharide (RAP) yield were studied by a Box–Behnken response surface design and the evaluation of its antioxidant potential. Three parameters that affect the productivity of UAE, such as extraction temperature (50–90 ◦C), extraction time (10–30 min), and solid–liquid ratio (1–2 g/mL), were examined to optimize the yield of the polysaccharide percentage. The chromatographic analysis revealed that the composition of monosaccharides was found to be glucose, galactose, mannose, arabinose, and fucose. The data were fitted to polynomial response models, applying multiple regression analysis with a high coefficient of determination value (R2 = 0.999). The data exhibited that the extraction parameters have significant effects on the extraction yield of polysaccharide percentage. Derringer’s desirability prediction tool was attained under the optimal extraction conditions (extraction temperature 66.75 ◦C, extraction time 19.72 min, and liquid–solid ratio 1.66 mL/g) with a desirability value of 1 yielded the highest polysaccharide percentage (11.56%), which was confirmed through validation experiments. An average of 11.09 ± 1.65% of polysaccharide yield was obtained in optimized extraction conditions with a 95.43% validity. The in vitro antioxidant effect of polysaccharides of R. arboreum was studied. The results showed that the RAP extract exhibited a strong potential against free radical damage

Myricetin Abrogates Cisplatin-Induced Oxidative Stress, Inflammatory Response, and Goblet Cell Disintegration in Colon of Wistar Rats

Cisplatin [cis-diamminedichloroplatinum II] is an extensively prescribed drug in cancer chemotherapy; it is also useful for the treatment of diverse types of malignancies. Conversely, cisplatin is associated with a range of side effects such as nephrotoxicity, hepatotoxicity, gastrointestinal toxicity, and so on. Myricetin (3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-4chromenone) is a very common natural flavonoid found in fruits, tea, and plants. It has been found to have high-value pharmacological properties and strong health benefits. To examine the role of myricetin in colon toxicity induced by cisplatin, we conducted a concurrent prophylactic study in experimental animals that were treated orally with myricetin for 14 days at two doses—25 and 50 mg/kg of body weight. On the 14th day, a single intraperitoneal injection of cisplatin (7.5 mg/kg body weight) was administered in all groups except control. The effects of myricetin in cisplatin-induced toxicity in the colon were assessed in terms of antioxidant status, phase-II detoxification enzymes, the level of inflammatory markers, and goblet cell disintegration. Myricetin was found to restore the level of all the antioxidant enzymes analyzed in the study. In addition, the compound ameliorated cisplatin-induced lipid peroxidation, increase in xanthine oxidase activity, and phase-II detoxifying enzyme activity. Myricetin also attenuated deteriorative effects induced by cisplatin by regulating the level of molecular markers of inflammation (NF-κB, Nrf-2, IL-6, and TNF-α), restoring Nrf-2 levels, and controlling goblet cell disintegration. The current study reinforces the conclusion that myricetin exerts protection in colon toxicity via up-regulation of inflammatory markers, improving anti-oxidant status, and protecting tissue damage

Computational Approaches for Identification of Potential Plant Bioactives as Novel G6PD Inhibitors Using Advanced Tools and Databases

In glucose metabolism, the pentose phosphate pathway (PPP) is the major metabolic pathway that plays a crucial role in cancer growth and metastasis. Although it has been pointed out that blockade of the PPP is a promising approach against cancer, in the clinical setting, effective anti-PPP agents are still not available. Dysfunction of the G6PD enzyme in this pathway leads to cancer development as this enzyme possesses oncogenic activity. In the present study, an attempt was made to identify bioactive compounds that can be developed as potential G6PD inhibitors. In the present study, 11 natural compounds and a controlled drug were taken. The physicochemical and toxicity properties of the compounds were determined via ADMET and ProTox-II analysis. In the present study, the findings of docking studies revealed that staurosporine was the most effective compound with the highest binding energy of −9.2 kcal/mol when docked against G6PD. Homology modeling revealed that 97.56% of the residues were occupied in the Ramachandran-favored region. The modeled protein gave a quality Z-score of −10.13 by ProSA tool. iMODS server provided significant insights into the mobility, stability and flexibility of the G6PD protein that described the collective functional protein motion. In the present study, the physical and functional interactions between proteins were determined by STRING. CASTp server determined the topological and geometric properties of the G6PD protein. The findings of the present study revealed that staurosporine could be developed as a potential G6PD inhibitor; however, further in vivo and in vitro studies are needed for further validation of these results

Achieving crop stress tolerance and improvement: an overview of genomic techniques

The inexorable exposure of plants to the combinations of abiotic stresses has affected the worldwide food supply. The crop improvement against these abiotic stresses has been captivating approach to increase the yield and enhance the stress tolerance. By using traditional and modern breeding methods, the characters that confer tolerance to these stresses were accomplished. No doubt genetic engineering and molecular breeding have helped in comprehending the intricate nature of stress response. Understanding of abiotic stress-involved cellular pathways provides vital information on such responses. On the other hand, genomic research for crop improvement has raised new assessments in breeding new varieties against abiotic stresses. Interpretation of responses of the crop plants under stress is of great significance by studying the main role of crops in food and biofuel production. This review presents genomic-based approaches revealing the complex networks controlling the mechanisms of abiotic stress tolerance, and the possible modes of assimilating information attained by genomic-based approaches due to the advancement in isolation and functional analysis of genes controlling the yield and abiotic stress tolerance are discussed

Aptamer based nanobiosensors: Promising healthcare devices

Nanobiosensors based on aptamer are extensively being studied as potent analytical tools in clinical analysis. These biosensors provide high sensitivity, fast response, specificity and desired portability in addition to simplicity and decreased cost compared to conventional methods. The purpose of this manuscript is to provide readers with an overview of current advances about electrochemical, electrochemiluminescent and photoelectrochemical aptasensors from the sea of available literature. These are mainly used for determination of protein-based biomarkers, especially for cancer diagnosis. Here in we have given special emphasis on nanosize-based aptasensors which have been reported to show considerable improvement in the analytical performance. Keywords: Nanobiosenors, Aptasensors, Electrochemical, Electrochemiluminescent, Photoelectrochemical, Nanomateria

Association Mechanism and Conformational Changes in Trypsin on Its Interaction with Atrazine: A Multi- Spectroscopic and Biochemical Study with Computational Approach

Atrazine (ATR) is a herbicide globally used to eliminate undesired weeds. Herbicide usage leads to various adverse effects on human health and the environment. The primary source of herbicides in humans is the food laced with the herbicides. The ATR binding to trypsin (TYP) was investigated in this study to explore its binding potential and toxicity. In vitro interaction of ATR with TYP was studied using multi-spectroscopic methods, molecular docking, and enzyme kinetics to explore the mechanism of binding for the TYP-ATR system. The TYP-ATR complex revealed binding constants (103 M−1), suggesting a moderate binding. The free energy for the TYP-ATR complexes was negative, suggesting a spontaneous interaction. Thermodynamic parameters enthalpy (ΔH) and entropy (ΔS) obtained positive values for the TYP-ATR system suggesting hydrophobic interactions in the binding process. Micro-environmental and conformational changes in TYP molecules were induced on interaction with ATR. Reduced catalytic activity of TYP was observed after interaction with ATR owing to the changes in the secondary structure of the TYP

Knowledge, Attitude and Perception of Pharmacy Students towards Pharmacogenomics and Genetics: An Observational Study from King Saud University

Pharmacists are considered among the most accessible healthcare workers in fundamental positions to implement new clinical initiatives, such as pharmacogenomics services. The scope of pharmacogenomics in improving health outcomes and the quality of health care is well-known. Implementation of such initiatives requires adequate knowledge, perception, and positive attitudes among pharmacists. A study was conducted on pharmacy students at King Saud University in Riyadh to analyze their attitudes, knowledge, and perceptions concerning pharmacogenomics to explore the feasibility of establishing full-time pharmacogenomics instruction and services. A cross-sectional study was carried out in one of the significant pharmacy schools of Saudi Arabia, using a simple questionnaire-based survey in pharmacy students pursuing Bpharm and PharmD courses to obtain preliminary information about pharmacogenomics among the surveyed population. The study’s secondary objective was to determine the perceived belief about pharmacogenomics implementation in clinical practice. Out of the total of 552 participants, 41.8% correctly defined pharmacogenomics and 81.3% understood that genetic change could lead to adverse reactions. More than half of the participants agreed that the FDA recommends pharmacogenomics testing for certain drugs. The knowledge about a year of use of pharmacogenomics in clinical practice was found to be very low; only 15.2% could correctly answer. Only 60% of students agreed on pharmacogenomics testing for selecting the therapy with the most negligible adverse effects. Due to the limited knowledge about and understanding of pharmacogenomics, there is a lack of interest among pharmacy students in implementing pharmacogenomics testing in clinical practice. Our study highlights the need for improving pharmacy students’ knowledge about pharmacogenomics and pharmacogenetics so that the implementation of pharmacogenomics testing in clinical practice will become easier. There is a need to introduce an up-to-date curriculum for pharmacy courses other pharmacogenomics-based health education programs in Saudi Arabia