Anti-arthritic studies of ethnomedicine Gaultheria trichophylla Royle extract and salicylate-rich fraction using complete Freud's adjuvant-induced rats: molecular docking and network pharmacology analysis.

Gaultheria trichophylla Royle is a traditional treatment for inflammatory conditions including arthritis. The objective was to evaluate the anti-arthritic activity of the extracts and salicylate-rich fractions through adjuvant-induced arthritis, histopathological analysis, radiological imaging, hematological, biochemical parameters along with using bioinformatic tools. In vivo anti-arthritic efficacy of the extract and SRF (at 100, 200, 300, and 150 mg/kg doses) was assessed using healthy albino rats. Molecular docking of identified compounds along with network pharmacology analysis helped to determine the route of action of drug. Both the extract and SRF showed dose-dependent anti-arthritic activity by decreasing the joint diameter, increase in pain threshold and body weight compared with negative control group. Along with SRF (150 mg/kg), EEGT (300 and 200 mg/kg) shows significant (P < 0.01) anti-arthritic activity by lowering levels of WBC, platelets, serum C-reactive protein (CRP), and rheumatoid factor (RF) and raising levels of RBC and Hb. The modified biochemical measures (AST, ALT, ALP, and total protein level) further supported the anti-arthritic action. Histopathology and radiology study showed that EEGT (300 and 200 mg/kg), SRF (150 mg/kg) and diclofenac (10 mg/kg) inhibited joint destruction. GCMS analysis showed the presence of methyl salicylate, sitosterol, calcifediol, and ergosta-5,22-dien-3-ol, acetate as important bioactive constituents. Moreover, as the significant node in the pharmacology network and docking against TNF-α, a classical therapeutic target in RA showed potential of G. trichophylla in treatment of RA. The results showed that G. trichophylla have effectively reduced the inflammation of the joints.

Reporting guidelines for precision medicine research of clinical relevance: the BePRECISE checklist.

Precision medicine should aspire to reduce error and improve accuracy in medical and health recommendations by comparison with contemporary practice, while maintaining safety and cost-effectiveness. The etiology, clinical manifestation and prognosis of diseases such as obesity, diabetes, cardiovascular disease, kidney disease and fatty liver disease are heterogeneous. Without standardized reporting, this heterogeneity, combined with the diversity of research tools used in precision medicine studies, makes comparisons across studies and implementation of the findings challenging. Specific recommendations for reporting precision medicine research do not currently exist. The BePRECISE (Better Precision-data Reporting of Evidence from Clinical Intervention Studies & Epidemiology) consortium, comprising 23 experts in precision medicine, cardiometabolic diseases, statistics, editorial and lived experience, conducted a scoping review and participated in a modified Delphi and nominal group technique process to develop guidelines for reporting precision medicine research. The BePRECISE checklist comprises 23 items organized into 5 sections that align with typical sections of a scientific publication. A specific section about health equity serves to encourage precision medicine research to be inclusive of individuals and communities that are traditionally under-represented in clinical research and/or underserved by health systems. Adoption of BePRECISE by investigators, reviewers and editors will facilitate and accelerate equitable clinical implementation of precision medicine.

An affordable label-free ultrasensitive immunosensor based on gold nanoparticles deposited on glassy carbon electrode for the transferrin receptor detection.

In recent decades, there has been a concerning and consistent rise in the incidence of cancer, posing a significant threat to human health and overall quality of life. The transferrin receptor (TfR) is one of the most crucial protein biomarkers observed to be overexpressed in various cancers. This study reports on the development of a novel voltammetric immunosensor for TfR detection. The electrochemical platform was made up of a glassy carbon electrode (GCE) functionalized with gold nanoparticles (AuNPs), on which anti-TfR was immobilized. The surface characteristics and electrochemical behaviors of the modified electrodes were comprehensively investigated through scanning electron microscopy, XPS, Raman spectroscopy FT-IR, electrochemical cyclic voltammetry and impedance spectroscopy. The developed immunosensor exhibited robust analytical performance with TfR fortified buffer solution, showing a linear range (LR) response from 0.01 to 3000 µg/mL, with a limit of detection (LOD) of 0.01 µg/mL and reproducibility (RSD <4 %). The fabricated sensor demonstrated high reproducibility and selectivity when subjected to testing with various types of interfering proteins. The immunosensor designed for TfR detection demonstrated several advantageous features, such as being cost-effective and requiring a small volume of test sample making it highly suitable for point-of-care applications.

The metabolic landscape of the bacteria Rhodococcus erythropolis used in the biodesulfurization of petroleum products: an emphasis on 2-hydroxybiphenyl.

Microorganisms produce diverse classes of metabolites under various physiological conditions. Many bacterial strains have been reported to carry out the process of desulfurization in a cost-effective manner by converting dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) and then using the 2-HBP as a carbon source for growth and development. Key rate-limiting factors and an increased concentration of 2HBP (400 µM) affect the biodesulfurization activity of bacteria through the produced metabolites. Thus, this study was designed to explore the nature of the metabolites produced by Rhodococcus erythropolis in the presence of DBT and 2HBP supplemented with a culture medium. A total of 330 metabolites were detected, and the key metabolites identified were 11Z-eicosaenoyl-EA, 1-carboxyethylisoleucine, 1(3)-glyceryl-PGF2alpha, taurine, 2-hydroxynicotinic acid, 4,4-dimethyl-14alpha-hydroxymethyl-5alpha-cholest-8-en-3beta-ol, and 10-nitrooleic acid. The supplementation of DBT and DBT-2HBP resulted in the differential regulation of these metabolites, either through downregulation or overexpression. Furthermore, at high concentrations of 2-HBP, 1-carboxyethylisoleucine, taurine, 2-hydroxynicotinic acid, and nicotinic acid were upregulated. This work proposes that the identified metabolites may play a role in bacteria-mediated desulphurization and could be beneficial in developing a cost-effective method of desulphurization for refining petroleum.

Multi-targeted therapeutic potential of stigmasterol from the Euphorbia ammak plant in treating lung and breast cancer.

Cancer is the most prevalent disease globally, which presents a significant challenge to the healthcare industry, with breast and lung cancer being predominant malignancies. This study used RNA-seq data from the TCGA database to identify potential biomarkers for lung and breast cancer. Tumor Necrosis Factor (TNFAIP8) and Sulfite Oxidase (SUOX) showed significant expression variation and were selected for further study using structure-based drug discovery (SBDD). Compounds derived from the Euphorbia ammak plant were selected for in-silico study with both TNFAIP8 and SUOX. Stigmasterol had the greatest binding scores (normalized scores of -8.53 kcal/mol and -9.69 kcal/mol) with both proteins, indicating strong stability in their binding pockets throughout the molecular dynamics' simulation. Although Stigmasterol first changed its initial conformation (RMSD = 0.5 nm with the starting conformation) in SUOX, it eventually reached a stable conformation (RMSD of 1.5 nm). The compound on TNFAIP8 showed a persistent shape (RMSD of 0.35 nm), indicating strong protein stability. The binding free energy of the complex was calculated using the MM/GBSA technique; TNFAIP8 had a ΔGTOTAL of -24.98 kcal/mol, with TYR160 being the most significant residue, contributing -2.52 kcal/mol. On the other hand, the SUOX complex had a binding free energy of -16.87 kcal/mol, with LEU151 being the primary contributor (-1.17 kcal/mol). Analysis of the complexes' free energy landscape unveiled several states with minimum free energy, indicating robust interactions between the protein and ligand. In its conclusion, this work emphasises the favourable ability of Stigmasterol to bind with prospective targets for lung and breast cancer, indicating the need for more experimental study.

Synthesis of carbon nanotubes-chitosan nanocomposite and immunosensor fabrication for myoglobin detection: An acute myocardial infarction biomarker.

The use of single-walled carbon nanotubes (SWCNTs) in biomedical applications is limited due to their inability to disperse in aqueous solutions. In this study, dispersed -COOH functionalized CNTs with N-succinylated chitosan (CS), greatly increasing the water solubility of CNTs and forming a uniformly dispersed nanocomposite solution of CNTs@CS. Coupling reagent EDC/NHS was used as a linker with the -COOH groups present on the N-succinylated chitosan which significantly improved the affinity of the CNTs for biomolecules. Myoglobin (Mb) is a promising biomarker for the precise assessment of cardiovascular risk, type 2 diabetes, metabolic syndrome, hypertension and several types of cancer. A high level of Mb can be used to diagnose the mentioned pathogenic diseases. The CNTs@CS-FET demonstrates superior sensing performance for Mb antigen fortified in buffer, with a wide linear range of 1 to 4000 ng/mL. The detection limit of the developed Mb immunosensor was estimated to be 4.2 ng/mL. The novel CNTs@CS-FET immunosensor demonstrates remarkable capability in detecting Mb without being affected by interferences from nonspecific antigens. Mb spiked serum showed a recovery rate of 100.262 to 118.55 % indicating great promise for Mb detection in clinical samples. The experimental results confirmed that the CNTs@CS-FET immunosensor had excellent selectivity, reproducibility and storage stability.

Prediction of anticancer peptides derived from the true lectins of Phoenix dactylifera and their synergetic effect with mitotane.

Background and aims: Cancer continues to be a significant source of both illness and death on a global scale, traditional medicinal plants continue to serve as a fundamental resource of natural bioactive compounds as an alternative source of remedies. Although there have been numerous studies on the therapeutic role of Phoenix dactylifera, the study of the role of peptides has not been thoroughly investigated. This study aimed to investigate the anticancer activity of lectin peptides from P. dactylifera using in silico and in vivo analysis. Methods: Different computational tools were used to extract and predict anticancer peptides from the true lectins of P. dactylifera. Nine peptides that are bioactive substances have been investigated for their anticancer activity against MCF-7 and T47D (two forms of breast cancer). To counteract the unfavorable effects of mitotane, the most potent peptides (U3 and U7) were combined with it and assessed for anticancer activity against MCF-7 and HepG2. Results: In silico analysis revealed that nine peptides were predicted with anticancer activity. In cell lines, the lowest IC50 values were measured in U3 and U7 against MCF-7 and T47D cells. U3 or U7 in combination with mitotane demonstrated the lowest IC50 against MCF-7 and HepG2. The maximum level of cell proliferation inhibition was 22% when U3 (500 µg/mL) and 25 µg/mL mitotane were combined, compared to 41% when 25 µg/mL mitotane was used alone. When mitotane and U3 or U7 were combined, it was shown that these bioactive substances worked synergistically with mitotane to lessen its negative effects. The combination of peptides and mitotane could be regarded as an efficient chemotherapeutic medication having these bioactive properties for treating a variety of tumors while enhancing the reduction of side effects.

Unlocking the Potential of High Entropy Alloys in Electrochemical Water Splitting: A Review.

The global pursuit of sustainable energy is focused on producing hydrogen through electrocatalysis driven by renewable energy. Recently, High entropy alloys (HEAs) have taken the spotlight in electrolysis due to their intriguing cocktail effect, broad design space, customizable electronic structure, and entropy stabilization effect. The tunability and complexity of HEAs allow a diverse range of active sites, optimizing adsorption strength and activity for electrochemical water splitting. This review comprehensively covers contemporary advancements in synthesis technique, design framework, and physio-chemical evaluation approaches for HEA-based electrocatalysts. Additionally, it explores design principles and strategies aimed at optimizing the catalytic activity, stability, and effectiveness of HEAs in hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. Through an in-depth investigation of these aspects, the complexity inherent in constituent element interactions, reaction processes, and active sites associated with HEAs is aimed to unravel. Eventually, an outlook regarding challenges and impending difficulties and an outline of the future direction of HEA in electrocatalysis is provided. The thorough knowledge offered in this review will assist in formulating and designing catalysts based on HEAs for the next generation of electrochemistry-related applications.

Virtual screening and site-directed mutagenesis-derived aptamers for precise Salmonella typhimurium prediction: emphasizing OmpD targeting and G-quadruplex stability.

The efficient detection of the foodborne pathogen Salmonella typhimurium has historically been hampered by the constraints of traditional methods, characterized by protracted culture periods and intricate DNA extraction processes for PCR. To address this, our research innovatively focuses on the crucial and relatively uncharted virulence factor, the Outer Membrane Protein D (OmpD) in Salmonella typhimurium. By harmoniously integrating the power of virtual screening and site-directed mutagenesis, we unveiled aptamers exhibiting marked specificity for OmpD. Among these, aptamer 7ZQS stands out with its heightened binding affinity. Capitalizing on this foundation, we further engineered a repertoire of mutant aptamers, wherein APT6 distinguished itself, reflecting unmatched stability and specificity. Our rigorous validation, underpinned by cutting-edge bioinformatics tools, amplifies the prowess of APT6 in discerning and binding OmpD across an array of Salmonella typhimurium strains. This study illuminates a transformative approach to the prompt and accurate detection of Salmonella typhimurium, potentially redefining boundaries in applied analytical chemistry and bolstering diagnostic precision across diverse research and clinical domains.Communicated by Ramaswamy H. Sarma.

In Silico Insights into the Arsenic Binding Mechanism Deploying Application of Computational Biology-Based Toolsets.

An assortment of environmental matrices includes arsenic (As) in its different oxidation states, which is often linked to concerns that pose a threat to public health worldwide. The current difficulty lies in addressing toxicological concerns and achieving sustained detoxification of As. Multiple conventional degradation methods are accessible; however, they are indeed labor-intensive, expensive, and reliant on prolonged laboratory evaluations. Molecular interaction and atomic level degradation mechanisms for enzyme-As exploration are, however, underexplored in those approaches. A feasible approach in this case for tackling this accompanying concern of As might be to cope with undertaking multivalent computational methodologies and tools. This work aimed to provide molecular-level insight into the enzyme-aided As degradation mechanism. AutoDock Vina, CABS-flex 2.0, and Desmond high-performance molecular dynamics simulation (MDS) were utilized in the current investigation to simulate multivalent molecular processes on two protein sets: arsenate reductase (ArsC) and laccase (LAC) corresponding arsenate (ART) and arsenite (AST), which served as model ligands to comprehend binding, conformational, and energy attributes. The structural configurations of both proteins exhibited variability in flexibility and structure framework within the range of 3.5-4.5 Å. The LAC-ART complex exhibited the lowest calculated binding affinity, measuring -5.82 ± 0.01 kcal/mol. Meanwhile, active site residues ILE-200 and HIS-206 were demonstrated to engage in H-bonding with the ART ligand. In contrast to ArsC, the ligand binding affinity of this bound complex was considerably greater. Additional validation of docked complexes was carried out by deploying Desmond MDS of 100 ns to capture protein and ligand conformation behavior. The system achieved stability during the 100 ns simulation run, as confirmed by the average P-L RMSD, which was ∼1 Å. As a preliminary test of the enzyme's ability to catalyze As species, corresponding computational insights might be advantageous for bridging gaps and regulatory consideration.

Fabrication of an affordable and sensitive corticosteroid-binding globulin immunosensor based on electrodeposited gold nanoparticles modified glassy carbon electrode.

Herein, we fabricated an ultrasensitive electrochemical immunosensor for the quantitative detection of corticosteroid-binding globulin (CBG). CBG is a protein that regulates glucocorticoid levels and is an important biomarker for inflammation. A decrease in CBG levels is a key biomarker for inflammatory diseases, such as septic shock. To enhance the electrochemical performance and provide a large surface area for anti-CBG immobilization, we functionalized the glassy carbon electrode surface with AuNPs. Electrochemical characterization methods including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the construction of the fabricated immunosensor. The electrochemical signal demonstrated a remarkable sensitivity to the CBG antigen, with a detection range from 0.01 to 100 µg/mL and a limit of detection of 0.012 µg/mL, making it suitable for both clinical and research applications. This label-free immunosensor offers significant advantages, including high sensitivity, low detection limits and excellent selectivity, making it a promising tool for detecting CBG in complex biological samples. Its potential applications include early disease diagnosis, treatment monitoring and studying CBG-related physiological processes.

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). METHODS: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. RESULTS: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. CONCLUSIONS: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

People living with type 2 diabetes (T2D) are more likely to develop problems with their heart or blood circulation, known as cardiovascular disease (CVD), than people who do not have T2D. However, it can be difficult to predict which people with T2D are most likely to develop CVD. This is because current approaches, such as blood tests, do not identify all people with T2D who are at an increased risk of CVD. In this study we reviewed published papers that investigated the differences between people with T2D who experienced CVD compared to those who did not. We found some indicators that could potentially be used to determine which people with T2D are most likely to develop CVD. More studies are needed to determine how useful these are. However, they could potentially be used to enable clinicians to provide targeted advice and treatment to those people with T2D at most risk of developing CVD.

Characterization of Salmonella enterica Biofilms and Antibiofilm Effect of Carvacrol and 2-Aminobenzimidazole.

Biofilm-associated foodborne Salmonella infections in poultry have become increasingly challenging for veterinarians, particularly in developing countries, and warrant thorough investigation. We assessed the biofilm-forming tendency of poultry isolates of Salmonella enterica, namely Salmonella Typhimurium (n = 23), Salmonella Infantis (n = 28), and Salmonella Heidelberg (n = 18), in nutrient-rich Rappaport-Vassiliadis Soya (RVS) peptone broth and nutrient-deficient diluted Tryptone Soya Broth (TSB). Seven of the tested isolates exhibited moderate biofilm formation in diluted TSB, whereas two showed such formation in RVS. In addition, the Congo red agar assay revealed curli and cellulose production in seven isolates. Fourteen specific biofilm-associated genes were analyzed identifying sdiA and seqA to be the most prevalent (100%), and glyA the least prevalent (69.5%). The prevalence of the genes bcsA and csgA was significantly lower in moderate and weak biofilm formers, respectively, as compared with nonbiofilm formers in RVS peptone broth. Furthermore, the compounds carvacrol and 2-aminobenzimidazole (2-ABI) effectively inhibited biofilm formation by Salmonella serovars in RVS peptone and TSB media, respectively. Whereas the antibiofilm activity of 2-ABI against Salmonella has not been reported previously, we determined its most effective concentration at 1.5 mM among tested antibiofilm treatments. These findings indicate that Salmonella strains prevalent in poultry farms have the potential to form biofilms, and the tested compounds should be further explored as supportive or alternative antimicrobials.

Label-free and ultrasensitive electrochemical transferrin detection biosensor based on a glassy carbon electrode and gold nanoparticles.

In this study, we developed a label-free and ultrasensitive electrochemical biosensor for the detection of transferrin (Tf), an important serum biomarker of atransferrinemia. The biosensor was fabricated by using glassy carbon electrode (GCE) and modified with gold nanoparticles (AuNPs) via electroless deposition. The electrochemical characteristics of the GCE-AuNPs biosensors were characterized using cyclic voltammetry and electrochemical impedance spectroscopy analysis. Differential pulse voltammetry was used for quantitative evaluation of the Tf-antigen by recording the increase in the anodic peak current of GCE-AuNPs biosensor. The GCE-AuNPs biosensor demonstrates superior sensing performance for Tf-antigen fortified in buffer, with a wide linear range of 0.1 to 5000 µg/mL and a limit of detection of 0.18 µg/mL. The studied GCE-AuNPs biosensor showed excellent sensitivity, selectivity, long-term storage stability and simple sensing steps without pretreatment of clinical samples. This GCE-AuNPs biosensor indicates great potential for developing a Tf detection platform, which would be helpful in the early diagnosis of atransferrinemia. The developed GCE-AuNPs biosensor holds great potential in biomedical research related to point of care for the early diagnosis and monitoring of diseases associated with aberrant serum transferrin levels. These findings suggest that the GCE-AuNPs biosensor has great potential for detecting other serum biomarkers.

New paracetamol hybrids as anticancer and COX-2 inhibitors: Synthesis, biological evaluation and docking studies.

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC50 ) values ranging from 1.51 to 6.31 µM and anti-COX-2 activity with IC50 = 0.29 µM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy.

Organochlorine pesticides disrupt T helper cell regulation and reduce IL-2 and IFN-γ favoring infection and production of autoantibodies among pemphigus patients.

The list of environmental factors that trigger autoimmune diseases in genetically susceptible individuals has grown in the recent years and is far from complete. The possible intervention of the environment in triggering these diseases is ever more perceived by the clinicians. This study investigated the effect of environmental factors like organochlorine pesticides (OCPs) on proportions of different T lymphocyte subsets and their cytokine secretion in-vitro among pemphigus patients, before and after specific immunosuppressive therapy. Higher levels of OCPs like ß-HCH (isoform of hexachlorohexane), α-endosulfan (a form of endosulfan) and p,p΄-DDE (a metabolite of o,p'-dichlorodiphenyltrichloroethane) were observed in the blood of pemphigus patients as compared to healthy controls. HCH and DDT exposure caused specific reduction in CD8+CD45RA+ and CD4+CD25+ T lymphocyte subpopulations in these patient PBMCs. A strong reduction in Th1 (IL-2 and IFN-γ) cytokines upon exposure to these OCPs in-vitro was also observed. These findings indicate that HCH and DDT have a significant impact on Th1 lymphocytes. Impaired production of these cytokines might favor infections and production of autoantibodies. We therefore speculate that the systemic absorption of the pesticide after the topical contact may be one of the factors triggering the immunological mechanism among pemphigus patients.

Insight to phytochemical investigation and anti-hyperlipidemic effects of Eucalyptus camaldulensis leaf extract using in vitro, in vivo and in silico approach.

Hyperlipidemia is a key risk factor mainly for hypertension and cardiac abnormalities. Previously eucalyptus plant (river red gum) had been used for its medicinal value for the treatment of many ailments. This study focused on phytochemical examination, investigation of an in vitro potential and in vivo effects in mice fed with high cholesterol diet, GC-MS analysis of extracts of Eucalyptus camaldulensis leaves and further confirmation of anti-hyperlipidemic potential of different constituents of plant extracts by using in silico technique. For in vitro study screening of different extracts of Eucalyptus camaldulensis leaves was performed by using pancreatic lipase enzyme inhibition assay. Ethanolic extract presented the highest potential among all the extracts by inhibiting pancreatic lipase having IC50-11.88 µg/mL. For in vivo study mice were fed with high cholesterol diet for induction of Hyperlipidemia. Water extract showed great anti-hyperlipidemic potential by reducing the level of cholesterol, triglycerides, low density lipoproteins and increasing high density lipoproteins level significantly (p < 0.05). Moreover, molecular docking and prime MM-GBSA study were applied for screening of compounds having anti-hyperlipidemic potential which showed that Alpha-cadinol was the lead compound for inhibition of pancreatic lipase enzyme having docking score (-6.604). The ADMET properties and toxicity profile of the top docked compounds were also detailed for ensuring their safety aspects. In this way in silico analysis substantiate the experimental findings by showing anti-hyperlipidemic potential in constituents of eucalyptus plant. Thus, there is a need of advanced research for isolation of active constituents having said anti-hyperlipidemic potential in the Eucalyptus camaldulensis plant.Communicated by Ramaswamy H. Sarma.

Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

ß Pore-forming Protein-based Evolutionary Divergence of Gnathostomata from Agnatha.

INTRODUCTION: The first vertebrates were jawless fish, or Agnatha, whose evolution diverged into jawed fish, or Gnathostomes, around 550 million years ago. METHODS: In this study, we investigated ß PFT proteins' evolutionary divergence of lamprey immune protein from Agnatha, reportedly possessing anti-cancer activity, into Dln1 protein from Gnathostomes. Both proteins showed structural and functional divergence, and shared evolutionary origin. Primary, secondary and tertiary sequences were compared to discover functional domains and conserved motifs in order to study the evolution of these two proteins. The structural and functional information relevant to evolutionary divergence was revealed using hydrophobic cluster analysis. RESULTS: The findings demonstrate that two membrane proteins with only a small degree of sequence identity can have remarkably similar hydropathy profiles, pointing towards conserved and similar global structures. When facing the lipid bilayer or lining the pore lumen, the two proteins' aerolysin domains' corresponding residues displayed a similar and largely conserved pattern. Aerolysin-like proteins from different species can be identified using a fingerprint created by PIPSA analysis of the pore-forming protein. CONCLUSION: We were able to fully understand the mechanism of action during pore formation through structural studies of these proteins.

Serum CRP biomarker detection by using carbon nanotube field-effect transistor (CNT-FET) immunosensor.

C-reactive protein (CRP) is produced by the liver in response to systemic inflammation caused by bacterial infection, trauma and internal organ failures. CRP serves as a potential biomarker in the precise diagnosis of cardiovascular risk, type-2 diabetes, metabolic syndrome, hypertension and various types of cancers. The pathogenic conditions indicated above are diagnosed by an elevated CRP level in the serum. In this study, we successfully fabricated a highly sensitive and selective carbon nanotube field-effect transistor (CNT-FET) immunosensor for the detection of CRP. The CNTs were deposited on the Si/SiO2 surface, between source-drain electrodes, afterwards modified with well-known linker PBASE and then anti-CRP was immobilized. This anti-CRP functionalized CNT-FET immunosensor exhibits a wide dynamic detection range (0.01-1000 µg/mL) CRP detection, rapid response time (2-3 min) and low variation (<3 %) which can be delivered as a low-cost and rapid clinical detection technology for the early diagnosis of coronary heart disease (CHD). For the clinical applications, our sensor was tested using CRP fortified serum samples and sensing performance was validated using enzyme-linked immune-sorbent assay (ELISA). This CNT-FET immunosensor will be helpful in taking over the complex laboratory-based expensive traditional CRP diagnostic procedures practiced in the hospitals.