Identification of therapeutic phytochemicals targeting B-cell lymphoma 2 (BCL2) as anti-acute myeloid leukemia agents: An in-silico approach

ackground: Acute myeloid leukemia (AML) is a deadly cancer. B cell lymphoma 2 (BCL2) is frequently upregulated in AML and plays a vital role in the viability of both AML and AML stem cells. This study aimed to identify novel phytochemicals against BCL2 and evaluate their pharmacokinetics and toxicity prediction using in-silico tools.Methods: In-silico screening of phytochemicals against BCL2 active site using the PyRx0.8 AutoDock tool, followed by in silico pharmacokinetic and toxicity predictions was performed. Protein-protein interaction analysis was performed using the STRING database for assessing the interactions between BCL2 and neighboring interacting proteins.Results: In total, 1106 terpenoid compounds were screened to evaluate their binding affinity toward BCL2. Five natural compounds demonstrated strong binding to the BCL2 protein after extensive screening, detailed interaction analysis, and visual inspections. Notably, these compounds had higher binding energies than the positive control (venetoclax). In addition, these compounds were found to bind to key BCL2 residues and possess good drug-like properties.Conclusions: The identified phytochemicals represent an important initial step in drug discovery for AML management. Experimental validation is required to optimize the identified phytochemicals as potential BCL2 inhibitors

A Review of the Effects of Omega-3 and Omega-6 on Alcoholic and Non-Alcoholic Fatty Liver

Non-alcoholic fatty liver disease is a type of fatty fat that causes an increase in alcohol consumption. Excessive alcohol consumption causes inflammation, and liver damage. The certain fatty acids (FAs) may be involved in this liver damage. Anti-inflammatory and blood lipid lowering effects are the effects of omega-3 unsaturated fatty acids (n-3 PUFAs). NAFLD is the hepatic manifestation of metabolic syndrome because obesity and insulin resistance are the main pathogenic factors of both diseases. NAFLD is a disease associated with metabolic syndrome. Most patients with NAFLD are obese, although the disease can also affect non-obese people. Metabolic and genetic factors play an important role in the occurrence of this disease. Oxidative stress, lipotoxicity and inflammation play a key role in the development of NAFLD. There is a lot of evidence for the therapeutic potential of omega-3 PUFAs fatty acids (n-3 PUFA), mainly docosahexaenoic acid and eicosatetraenoic acid in the treatment of metabolic diseases due to their antioxidant and anti-inflammatory properties. Therefore, in this review article, we examined the effects of omega-3 and omega-6 on alcoholic and non-alcoholic fatty liver disease

Possible correlations between SH2B3 rs2078863 gene polymorphism, lifestyle, food habits and nutritional intake of Minangkabau females with hypertension

Background: Hypertension is the commonest cardiovascular risk factor and a leading cause of death worldwide.  Several genetic variants are known to be involved in the pathogenesis of this disease. this study aimed to determine the relationship between the SH2B3 rs2078863 gene variants and hypertension in Minangkabau women.Methods: In total, 190 women aged 18-45 years old participated in this study. Patient data, including weight, height, Body Mass Index (BMI), and blood pressure examinations, were collected, and interviews regarding their nutrient intake and physical activity were assessed with the Semi-Quantitative Food Frequency Questionnaire (SQ-FFQ) and the Global Physical Activity Questionnaire (GPAQ) questionnaires. Blood was collected from peripheral veins, followed by DNA isolation and genotyping examination using the Kompetitive Allele Specific PCR (KASP) method.Results: TT genotype in SH2B3 rs2078863 was observed to be more at risk of suffering from hypertension compared to the CC+CT genotype ((ꭓ2 (1, n=190)=8.442 p=.004, phi=.21, OR=2.48). The regression logistic analysis revealed the role of obesity, low physical activity, and age as risk factors for hypertension in the studied population (p<0.05).Conclusion: In conclusion, the SH2B3 gene variant and lifestyle factors related to obesity, and low physical activity, increase the risk of hypertension

Green Nano-synthesis: Salix alba Bark-Derived Zinc Oxide Nanoparticle and their nematicidal Efficacy against root knot nematode Meloidogyne incognita

Background: Plant parasitic nematodes (PPNs) are considered major agriculture pests, causing significant damage to crops by directly targeting the plant root system to prevent water and nutrient uptake. One of its major species, Meloidogyne incognita, is considered a serious threat to agriculture crop production worldwide. The current study was intended to evaluate the potential of Nanoparticles synthesized from Salix alba bark extract as nematicidal agent.Methods: Phytochemical analyses of Salix alba bark extract were conducted, and nanoparticles of the same extract were synthesized and characterized using UV-vis spectroscopy, XRD (X-Ray Diffraction), SEM (Scanning Electron Microscopy) and EDX (Energy Dispersive X-ray Spectroscopy) techniques. Results: The qualitative phytochemical analysis of Salix alba bark extract revealed the presence of phenolics, flavonoids, reducing sugars, and saponins. When applied on juveniles of the plant parasitic nematode Meloidogyne incognita, the nanoparticles demonstrated a dose and time-dependent impact. After 24 hours, the highest concentration (1000 µg/ml) of nanoparticles exhibited the greatest mortality, reaching 82.2%, while the lowest concentration resulted in a mortality rate of 34.5%. Similarly, at the 48-hour mark, the highest mortality (92.2%) was observed with 1000 µg/ml of nanoparticles, whereas the lowest concentration yielded a mortality rate of 54.5%. Extending the observation period to 72 hours, the mortality rate peaked at 98.33% with the highest nanoparticle concentration (1000 µg/ml), and the lowest mortality rate was recorded at the lowest dose, amounting to 72.5%. These results underscore the dose and time-dependent efficacy of Salix alba bark-derived nanoparticles against Meloidogyne incognita. Conclusion: Our findings suggest that zinc oxide nanoparticles synthesized from Salix alba bark can be an effective agent against plant parasitic nematode Meloidogyne incognita. Further experiments are recommended to study the impact of these nanoparticles on other biotic stresses

Gram Negative bacteria and their Antibiotic Resistance: A Bibliometric Analysis

Background: Antibiotics are compounds made from microorganisms that destroy or prevent the growth of other microbes. The constant failure to engineer new antibiotics and imprudent usage of antibiotics resulted in the rise of antibiotics. In 2017, the World Health Organization released a list of the most pathogenic bacteria having the highest resistance against antibiotics which also included many Gram-Negative bacteria. In this study, we reviewed the data on publications on antibiotic resistant (ABR) Gram-negative bacteria by bibliometrics.Methods: The data from 2003 to 2022 were retrieved from the Web of Science and used further for statistical analysis. Both qualitative and quantitative analysis of the characteristics of publications, authors, top countries, leading journals, funding agencies and collaboration aspects.Result: The results showed a total of 10,350 publications with 7.94% annual growth rate in a linear pattern and 23.71 average citations per document on the subject. Lists of the most cited papers and papers with ranking by highest total citations per year were also retrieved. 98% of articles were published in English. Greater research output is from developed countries i.e., USA, China, India, England, Spain, Iran, Italy, Germany, and Japan. USA has the highest number of publications, citations, and Single Country Publications. USA is also the top country to have the highest collaborations with other countries.Conclusion: The study is suggestive for most developing and least developed countries to develop collaborations with researchers from developed countries, especially the USA and UK having domination in research productivity and sources of funding. The results of this study may provide potential prospects for the study of ABR Gram-negative bacteria in the future

Identification of potential inhibitors targeting DNA adenine methyltransferase of Klebsiella pneumoniae for antimicrobial resistance management: a structure-based molecular docking study

Background: Klebsiella pneumoniae is an important opportunistic pathogen that frequently causes nosocomial infections. Notably, this bacterium has emerged as a major problem in hospital settings because of its acquisition of resistance to carbapenems. The majority of antibiotics act by targeting crucial pathways within bacterial cells. However, due to the development of resistance mechanisms, the efficiency of these antibiotics has decreased. Therefore, this study focused on a putative protein (DNA adenine methyltransferase; Dam) found in K. pneumoniae that encompasses a DNA methylation protein domain, indicating a novel potential target for pharmacological intervention. DNA methylation affects bacterial virulence attenuation.Methods: In the unavailability of a 3D structure for Dam protein in protein database, a 3D model was generated using SWISS-MODEL server and validated using computational tools. Following that, screening was performed against the Dam protein using a set of 2706 phytochemicals obtained from the ZINC database using PyRx0.8. ProTox-II platform was used to predict the physicochemical properties and various toxicity endpoints.Results: Among the screened compounds, ZINC4214775, ZINC4095704, and ZINC4136964 had higher binding affinity for the Dam and interacted with its active site residues. The computational analyses of these three identified hits indicate that their predicted properties were within an acceptable range for evaluating toxicity. In addition, a toxicity radar chart showed that these hits were within an acceptable range.Conclusions: These compounds have the potential to act as Dam inhibitors and could be investigated further for managing antimicrobial resistance in K. pneumoniae

Isolation and identification of a mycotoxin produced by Aphanoascus terreus

Background: Keratinophilic fungi prefer keratin-rich materials such as; horn, hoof, and beak of birds for the purposes of growth and reproduction, they utilize keratin as a source of carbon. Mycotoxins, which are produced as byproducts by fungi, are dangerous to both human and animal health. This research aims to isolate and identify Aphanoascus terreus fungi from the soil as well as determine their potential to create mycotoxins.Methods: In January–April 2022, 45 soil samples were randomly collected from southern Iraq to isolation and identification of keratinophilic fungi, the hair bait method and molecular techniques were used also, detection of mycotoxin achieved by TLC technique then experimental injection in vivo.Results: The findings showed that 12 (66.7%) out of 18 soil samples that tested positive for the genus Aphanoascus belonged to the species A. terreus. When these isolates were compared to NCBI using PCR sequencing, they were 99% matched. In addition, all these isolates show the capacity to create a range of unidentified secondary metabolites with a variety of colors and flow rates. Only one compound was studied that appeared with a turquoise hue, so we named it A. terreus  T (ATT), which has an Rf. of 18.7 cm. The analysis of secondary metabolites with the aid of FTIR and GC-MS chemical tests indicated possibilities; the most probable is that the ATT is an acidic compound. Visual examinations of the skin of rats injected with ATT showed no obvious abnormalities. Microscopically, they appeared normal as well, but with mild inflammatory signs around the hair follicles.Conclusion: The outcomes represent the first international registration ever made in accordance with what is known about the production of a mycotoxin from A. terreus. This finding is considered the first reference regarding mycotoxin production from A. terreus

Acceptability Test of Modified Transglutaminase Gelatin from Striped Catfish (Pangasius hypophthalmus) Skin Based on Organoleptic and Toxicology

Background: Skin is one of the abundance side products of the striped catfish (Pangasius hypophthalmus) fillet industry in tropical countries. The previous histological study revealed that the skin of striped catfish contains high collagens which has the potential to supply the increasing halal gelatin demands. However, the texture of striped catfish skin gelatin (SCSG) at room temperature is mushy. This can be enhanced by the transglutaminase (TG) modification. SCSG modified with TG (SCSG_TG) needs to be tested for safety and consumer acceptance before being marketed. The research aims to decide the level of acute toxicity of SCSG_TG in mice (Mus musculus) and discover the organoleptic quality of SCSG_TG.Methods: Striped catfish skin gelatin modified with transglutaminase (SCSG_TG) was acquire by CH3COOH (acid) and NaOH (base) extraction at a temperature of 58°C. Toxicity tests using mice were worked by the Limit Test Procedure of the Organization for Economic Cooperation and Development (OECD) and then analyzed descriptively and qualitatively. While organoleptic tests were worked using hedonic assessment and the Friedman test.Results: The result shows SCSG_TG did not induce any toxic effects or death in mice. SCSG_TG 10 mg film was the most favored treatment group by the panelists (4.9-6.5) compared with SCSG_TG 0 mg (3.8-6.0) and SCSG_TG 50 mg film (4.1-6.3).Conclusion: Hence, the striped catfish skin gelatin film modified with transglutaminase (SCSG_TG) was declared safe, non-toxic, and accepted according to the organoleptic assessment that has met the standard ("dislike" criteria <25%)

Plausible inhibitors of malaria parasite Plasmodium falciparum 3D7 ATP-dependent DNA helicase

Background: Plasmodium falciparum is a  parasite (protozoa) of humans, & the lethal species of Plasmodium that affects malaria in humans. In the lack of a medically validated malaria vaccine, nearby are merely a few inexpensive medications available for therapy. Studies of diverse enzymes used in pharmaceutical drug discovery become essential aspects. The theoretical analysis helps to screen novel drug candidates.Methods: Here we have optimized three biologically active compounds, netropsin, nogalamycin, and novobiocin, and also carried out a molecular docking study with the protein ATP-dependent DNA helicase (UvrD) Plasmodium falciparum 3D7.Results: The plasmoDB id of the designated protein is PF3D7-0514100. Our calculations show that netropsin, nogalamycin, and novobiocin can have an affinity with the Plasmodium falciparum.Conclusion: Our study also predicted that novobiocin would give a better result with this protein than netropsin and nogalamycin. The frontier molecular orbitals & electrostatic potential (MEP) maps also support the higher activity of the novobiocin compound

Identification of Natural Compounds as CTX-M-15 Inhibitors for the Management of Multidrug-Resistant Bacteria: An in-silico study

Background: Antibiotic resistance is a major global threat to the efficacy of bacterial infection treatment. Resistance to beta-lactam antibiotics in bacteria is primarily caused by the production of extended-spectrum-lactamases, with the CTX-M variant, particularly CTX-M-15, being the most common. The need for an effective CTX-M-15 inhibitor is currently pressing.Methods: This study screened a library of natural compounds from the ZINC database against the CTX-M-15 protein using the PyRx 0.8 tool. The SwissADME web platform was used to predict the ADMET properties of the five most promising compounds.Result: The identified hits compounds, ZINC1857626342, ZINC403692, ZINC408773, ZINC57926, and ZINC790938591 exhibited strong binding with CTX-M-15. These compounds interacted with crucial catalytic site residues in the CTX-M-15 protein, particularly Ser70 and Ser130. Notably, the binding energies of these compounds were higher than those of the reference compound avibactam. Furthermore, they exhibited pharmacologically favorable characteristics.Conclusion: These compounds show promise as potential CTX-M-15 inhibitors to combat bacterial resistance. However, more experimental research is needed to optimize these compounds for their role as CTX-M-15 inhibitors