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Phthalates exposure and attention-deficit/hyperactivity disorder in children: a systematic review of epidemiological literature

Praveena SM, Munisvaradass R, Masiran R, Rajendran RK, Lin CC, Kumar S

Environ Sci Pollut Res Int, 2020 Dec;27(36):44757-44770.
PMID: 32895790 DOI: 10.1007/s11356-020-10652-z

Epidemiological studies have proven that children mental health can be affected by environmental pollutants which are believed to be visible in the form of psychological disorder later in their childhood. Moreover, the effects of children mental health are evidently clear in the case of phthalates which have been observed to increase psychological disorder, specifically attention-deficit hyperactivity disorder (ADHD). Hence, the present study aims to conduct a systematic review and provide an overview of the existing literature on the association between urinary phthalate metabolite concentrations and ADHD symptoms among children by emphasizing the confounding factors and limitations. Additionally, this review addressed the possible phthalate mechanism insights in human body including its impact on ADHD symptoms. In this case, 16 epidemiological studies (five cross-sectional, nine cohort and two case control studies) that met all the inclusion criteria were selected out of the total of 427 papers screened to show varying quantitative associations between phthalate exposure and ADHD symptoms among children with confounding factors and limitations in the existing studies in regard to the exposure and outcomes. This review also attempted to present possible explanation on phthalate mechanism in children body and its connection on neurodevelopment and ADHD symptom development which remains unclear in most of the studies. Finally, it is highly recommended for further research to carefully design cohort studies from prenatal to later childhood development with a complete sample size in order to understand phthalate impacts on children health.
Preanalytical Errors in Clinical Laboratory Testing at a Glance: Source and Control Measures

Nordin N, Ab Rahim SN, Wan Omar WFA, Zulkarnain S, Sinha S, Kumar S, et al.

Cureus, 2024 Mar;16(3):e57243.
PMID: 38559530 DOI: 10.7759/cureus.57243

The accuracy of diagnostic results in clinical laboratory testing is paramount for informed healthcare decisions and effective patient care. While the focus has traditionally been on the analytical phase, attention has shifted towards optimizing the preanalytical phase due to its significant contribution to total laboratory errors. This review highlights preanalytical errors, their sources, and control measures to improve the quality of laboratory testing. Blood sample quality is a critical concern, with factors such as hemolysis, lipemia, and icterus leading to erroneous results. Sources of preanalytical errors encompass inappropriate test requests, patient preparation lapses, and errors during sample collection, handling, and transportation. Mitigating these errors includes harmonization efforts, education and training programs, automated methods for sample quality assessment, and quality monitoring. Collaboration between laboratory personnel and healthcare professionals is crucial for implementing and sustaining these measures to enhance the accuracy and reliability of diagnostic results, ultimately improving patient care.
Red Cell Distribution Width and Mean Corpuscular Volume Alterations: Detecting Inflammation Early in Occupational Cement Dust Exposure

Ahmad R, Haq MA, Sinha S, Lugova H, Kumar S, Haque M, et al.

Cureus, 2024 May;16(5):e60951.
PMID: 38784687 DOI: 10.7759/cureus.60951

Introduction Cement dust emitted during cement manufacture consists of toxic components. Occupational cement dust exposure may cause inflammation in the human body, which may be detected early by observing changes in blood parameters such as red blood cell distribution width (RDW) and mean corpuscular volume (MCV). Objectives The study aims to observe the effect of occupational cement dust exposure on RDW and MCV. Methods This study was performed in the Department of Physiology of Dhaka Medical College, Dhaka, Bangladesh, and a factory in Munshiganj, Bangladesh, from September 2017 to August 2018. Ninety-two participants between 20 and 50 years were included (46 subjects were occupationally exposed to cement dust, and 46 were not exposed to cement dust). A pre-designed questionnaire was used for data collection. An independent sample t-test was used to analyze basic information, such as blood pressure and BMI. The multivariate regression model was used to analyze the effect of cement dust exposure on the study group. The impact of cement dust exposure duration was analyzed using the multivariate regression model. The level of significance was p < 0.05. The statistical analysis was performed using STATA-15 (StataCorp, College Station, TX), and the graphical presentation used GraphPad Prism v8.3.2. Results The cement dust-exposed participants had a significantly higher value of MCV by 1.19 fi (95% CI = 0.02, 4.84; p = 0.049) and a 5.92% increase in RDW (95% CI = 5.29, 6.55; p < 0.001) than that of the control group. Conclusion The study reveals that exposure to cement dust causes significant changes in RDW and MCV. These changes may indicate hemolysis due to inflammation.
Fulltext Unmasking the Hidden Burden: A Delayed Diagnosis of Leprosy Patients With Grade 2 Disability and Its Effects on the Healthcare System in Bangladesh

Sinha S, Haq MA, Ahmad R, Banik S, Kumar S, Haque M

Cureus, 2024 Apr;16(4):e58708.
PMID: 38651088 DOI: 10.7759/cureus.58708

Introduction Leprosy remains a significant cause of preventable disability worldwide. Early diagnosis and treatment of leprosy are critical not only to stop its spread but also to prevent physical and social complications and reduce the disease burden. Objectives The study aims to evaluate the factors that lead to a delayed leprosy diagnosis. Methods This study was conducted in the outpatient departments of Leprosy Control Institute and Hospital, Dhaka, Bangladesh, and at Medical College for Women and Hospital, Dhaka, Bangladesh, from March 2023 to June 2023. A total number of 252 male (148) and female (104) patients were selected with any sign of leprosy, including disability, age ranging from 15 to 74 years. Data was collected in a pre-designed structured questionnaire by the researchers. To assess the risk of independent exposures of Grade 2 leprosy disabilities, we used a logistic regression model. A chi-square test showed the association between significant effects and leprosy disabilities. A p-value of 0.05 was considered as significant. For statistical analysis, STATA version 15 (StataCorp LLC, College Station, Texas, USA) was used. Results The study participants exhibited a higher percentage of disability, with a rate of 25.8% for Grade 2 disabilities. In addition to this, males represented a more considerable proportion, 58.7%, than females among leprosy and disability patients across all levels of disability. In our study, lack of money and painless symptoms showed a significant association (p<0.001) with Grade 2 disability. Conclusion The study reveals that Grade 2 disabilities are more common in males and are particularly prevalent in lower socioeconomic groups.
Prediction of preterm birth in growth-restricted and appropriate-for-gestational-age infants using maternal PlGF and the sFlt-1/PlGF ratio-A prospective study

Hong J, Crawford K, Cavanagh E, da Silva Costa F, Kumar S

BJOG, 2024 Jul;131(8):1089-1101.
PMID: 38196326 DOI: 10.1111/1471-0528.17752

OBJECTIVE: To assess the utility of placental growth factor (PlGF) levels and the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA).
DESIGN: Prospective, observational cohort study.
SETTING: Tertiary maternity hospital in Australia.
POPULATION: There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32+0 weeks) and 109 (30.0%) late FGR (≥32+0 weeks).
METHODS: Maternal serum PlGF and sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt-1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt-1/PlGF ratio to the time of birth or censoring.
MAIN OUTCOME MEASURES: The primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained.
RESULTS: The early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p
Fulltext Multireceptor Analysis for Evaluating the Antidiabetic Efficacy of Karanjin: A Computational Approach

Nag S, Stany B, Mishra S, Kumar S, Mohanto S, Ahmed MG, et al.

Endocrinol Diabetes Metab, 2024 Jul;7(4):e509.
PMID: 38982323 DOI: 10.1002/edm2.509

BACKGROUND: Diabetes mellitus, notably type 2, is a rising global health challenge, prompting the need for effective management strategies. Common medications such as metformin, insulin, repaglinide and sitagliptin can induce side effects like gastrointestinal disturbances, hypoglycemia, weight gain and specific organ risks. Plant-derived therapies like Karanjin from Pongamia pinnata present promising alternatives due to their historical use, holistic health benefits and potentially fewer adverse effects. This study employs in silico analysis to explore Karanjin's interactions with diabetes-associated receptors, aiming to unveil its therapeutic potential while addressing the limitations and side effects associated with conventional medications.
METHODOLOGY: The research encompassed the selection of proteins from the Protein Data Bank (PDB), followed by structural refinement processes and optimization. Ligands such as Karanjin and standard drugs were retrieved from PubChem, followed by a comprehensive analysis of their ADMET profiling and pharmacokinetic properties. Protein-ligand interactions were evaluated through molecular docking using AutoDockTools 1.5.7, followed by the analysis of structural stability using coarse-grained simulations with CABS Flex 2.0. Molecular dynamics simulations were performed using Desmond 7.2 and the OPLS4 force field to explore how Karanjin interacts with proteins over 100 nanoseconds, focusing on the dynamics and structural stability.
RESULTS: Karanjin, a phytochemical from Pongamia pinnata, shows superior drug candidate potential compared to common medications, offering advantages in efficacy and reduced side effects. It adheres to drug-likeness criteria and exhibits optimal ADMET properties, including moderate solubility, high gastrointestinal absorption and blood-brain barrier penetration. Molecular docking revealed Karanjin's highest binding energy against receptor 3L2M (Pig pancreatic alpha-amylase) at -9.1 kcal/mol, indicating strong efficacy potential. Molecular dynamics simulations confirmed stable ligand-protein complexes with minor fluctuations in RMSD and RMSF, suggesting robust interactions with receptors 3L2M.
CONCLUSION: Karanjin demonstrates potential in pharmaceutical expansion for treating metabolic disorders such as diabetes, as supported by computational analysis. Prospects for Karanjin in pharmaceutical development include structural modifications for enhanced efficacy and safety. Nanoencapsulation may improve bioavailability and targeted delivery to pancreatic cells, while combination therapies could optimize treatment outcomes in diabetes management. Clinical trials and experimental studies are crucial to validate its potential as a novel therapeutic agent.
Fulltext In-silico molecular design of heterocyclic benzimidazole scaffolds as prospective anticancer agents

Tahlan S, Kumar S, Ramasamy K, Lim SM, Shah SAA, Mani V, et al.

BMC Chem, 2019 Dec;13(1):90.
PMID: 31384837 DOI: 10.1186/s13065-019-0608-5

Benzimidazole is a valuable pharmacophore in the field of medicinal chemistry and exhibit wide spectrum of biological activity. Molecular docking technique is routinely used in modern drug discovery for understanding the drug-receptor interaction. The selected data set of synthesized benzimidazole compounds was evaluated for its in vitro anticancer activity against cancer cell lines (HCT116 and MCF7) by sulforhodamine B (SRB) assay. Further, molecular docking study of data set was carried out by Schrodinger-Maestro v11.5 using CDK-8 (PDB code: 5FGK) and ER-alpha (PDB code: 3ERT) as possible target for anticancer activity. Molecular docking results demonstrated that compounds 12, 16, N9, W20 and Z24 displayed good docking score with better interaction within crucial amino acids and corelate to their anticancer results. ADME results indicated that compounds 16, N9 and W20 have significant results within the close agreement of the Lipinski's rule of five and Qikprop rule within the range and these compounds may be taken as lead molecules for the discovery of new anticancer agents.
Fulltext Image-based phenotyping of seed architectural traits and prediction of seed weight using machine learning models in soybean

Duc NT, Ramlal A, Rajendran A, Raju D, Lal SK, Kumar S, et al.

Front Plant Sci, 2023;14:1206357.
PMID: 37771485 DOI: 10.3389/fpls.2023.1206357

Among seed attributes, weight is one of the main factors determining the soybean harvest index. Recently, the focus of soybean breeding has shifted to improving seed size and weight for crop optimization in terms of seed and oil yield. With recent technological advancements, there is an increasing application of imaging sensors that provide simple, real-time, non-destructive, and inexpensive image data for rapid image-based prediction of seed traits in plant breeding programs. The present work is related to digital image analysis of seed traits for the prediction of hundred-seed weight (HSW) in soybean. The image-based seed architectural traits (i-traits) measured were area size (AS), perimeter length (PL), length (L), width (W), length-to-width ratio (LWR), intersection of length and width (IS), seed circularity (CS), and distance between IS and CG (DS). The phenotypic investigation revealed significant genetic variability among 164 soybean genotypes for both i-traits and manually measured seed weight. Seven popular machine learning (ML) algorithms, namely Simple Linear Regression (SLR), Multiple Linear Regression (MLR), Random Forest (RF), Support Vector Regression (SVR), LASSO Regression (LR), Ridge Regression (RR), and Elastic Net Regression (EN), were used to create models that can predict the weight of soybean seeds based on the image-based novel features derived from the Red-Green-Blue (RGB)/visual image. Among the models, random forest and multiple linear regression models that use multiple explanatory variables related to seed size traits (AS, L, W, and DS) were identified as the best models for predicting seed weight with the highest prediction accuracy (coefficient of determination, R2=0.98 and 0.94, respectively) and the lowest prediction error, i.e., root mean square error (RMSE) and mean absolute error (MAE). Finally, principal components analysis (PCA) and a hierarchical clustering approach were used to identify IC538070 as a superior genotype with a larger seed size and weight. The identified donors/traits can potentially be used in soybean improvement programs.
Fulltext Gingival Crevicular Blood Glucose as a Novel Method for Screening Diabetes Mellitus in Periodontally Compromised Patients

Patel C, Dave B, Patel R, Kumar S, Dattani V, Joshi S, et al.

Cureus, 2023 May;15(5):e39444.
PMID: 37250602 DOI: 10.7759/cureus.39444

INTRODUCTION: Patients with periodontitis are significantly more likely to have undetected diabetes mellitus (DM). Self‑monitoring devices like glucometers provide a simple method for rapid monitoring of the glucose level in blood by utilizing a blood sample from the finger, but this method requires puncturing to obtain blood. Bleeding from the gingival sulcus, obtained during oral hygiene examination, can be utilized for screening DM patients. Therefore, this study was performed with the aim of determining the efficacy of gingival crevicular blood as a non-invasive screening method for DM patients, as well as correlating and comparing gingival crevicular blood glucose (GCBG) levels with finger capillary blood glucose (FCBG) and fasting blood glucose (FBG) among non-diabetic and diabetic group patients.
METHODS: In this cross-sectional comparative study, a total of 120 participants having moderate to severe gingivitis/periodontitis with an age range of 40 to 65 years were divided into two groups on the basis of FBG range taken from an antecubital vein: non-diabetic (≤126, n=60) and diabetic (≥126, n=60) groups. Blood oozing during the routine periodontal examination from the periodontal pocket was recorded using a test strip of a glucose self-monitoring device (AccuSure®Simple) as GCBG. Concomitantly FCBG was collected from the fingertip. These three parameters were statistically analyzed using the Student's t-test and the one-way ANOVA test and correlated with Pearson's correlation coefficient for both groups.
RESULTS: The mean and standard deviation for the three parameters GCBG, FBG, and FCBG were 93.78±12.03, 89.98±13.22, and 93.08±15.56, respectively, for the non-diabetic group and 154.52±45.05, 159±47.00, and 162.23±50.60 subsequently for the diabetic group. Comparing glucose level parameters among the non-diabetic and diabetic groups suggests a significant difference with the p-value <0.001*(inter-group). ANOVA test was done for both groups suggesting no significant difference among these three methods of measuring blood glucose level, where the p-value found was 0.272 for the non-diabetic and 0.665 for the diabetic group (intra-group comparison). Pearson's correlation values suggested a good positive correlation for the non-diabetic group, with parameters GCBG and FBG (r=0.864), GCBG and FCBG (r=0.936), and FBG and FCBG (r=0.837). The diabetic group's Pearson's correlation suggested a highly significant positive correlation between three different methods in which GCBG and FBG (r=0.978), GCBG and FBG (r=0.977), and FBG and FCBG (r= 0.982).
CONCLUSION: Blood oozing from the periodontal pocket during routine oral hygiene examination can be utilized by dental healthcare professionals to screen pre-diabetic patients which can be used as a simple and less invasive method for DM patients.
Brain Tumor Classification Using Deep Neural Network and Transfer Learning

Kumar S, Choudhary S, Jain A, Singh K, Ahmadian A, Bajuri MY

Brain Topogr, 2023 Apr 15.
PMID: 37061591 DOI: 10.1007/s10548-023-00953-0

In the field of medical imaging, the classification of brain tumors based on histopathological analysis is a laborious and traditional approach. To address this issue, the use of deep learning techniques, specifically Convolutional Neural Networks (CNNs), has become a popular trend in research and development. Our proposed solution is a novel Convolutional Neural Network that leverages transfer learning to classify brain tumors in MRI images as benign or malignant with high accuracy. We evaluated the performance of our proposed model against several existing pre-trained networks, including Res-Net, Alex-Net, U-Net, and VGG-16. Our results showed a significant improvement in prediction accuracy, precision, recall, and F1-score, respectively, compared to the existing methods. Our proposed method achieved a benign and malignant classification accuracy of 99.30 and 98.40% using improved Res-Net 50. Our proposed system enhances image fusion quality and has the potential to aid in more accurate diagnoses.
Fulltext Bioaccumulation and potential sources of heavy metal contamination in fish species in River Ganga basin: Possible human health risks evaluation

Maurya PK, Malik DS, Yadav KK, Kumar A, Kumar S, Kamyab H

Toxicol Rep, 2019;6:472-481.
PMID: 31193923 DOI: 10.1016/j.toxrep.2019.05.012

This paper assesses the potential human health risks posed by five heavy metals (Zn, Pb, Cu, Cd, and Cr) found in seven most consumable fish species (Cirrhinus mrigala, Cirrhinus reba, Catla catla, Lebio rohita, Crossocheilus latius, Clupisoma garua, and Mystus tengara) collected from local markets of Varanasi, Allahabad, Mirzapur, and Kanpur of Uttar Pradesh, India. The Cu concentration was found at Varanasi (4.58 mg/l), Allahabad (2.54 mg/l), and Mirzapur (2.54 mg/l). Pb was recorded 0.54, 0.62, 0.85, and 0.24 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cd concentration was recorded 0.54, 0.68, 0.78, and 0.85 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cr, Cd, and Pb concentrations in the river water were observed over the prescribed safe limits at all sampling sites, while Cu concentration was higher than the standards at all sites except Kanpur. However, Zn was observed under the permissible limits (15 mg/l) at all sampling sites. In case of fish tissues, WHO reported the concentration of Pb, Cd, and Cr higher than the prescribed safe limits. The results determined that the highest heavy metals accumulation was found settled in the liver of all selected fish species. Zn ranked the highest quantity, which was found in fish tissues with the concentration of 32.41 ± 2.55 μg/g in the gill of C. catla and 4.77 ± 0.34 μg/g in the gill C. Reba. The metals followed the magnitude order of Zn > Pb > Cu > Cd > Cr in selected fish tissues.
Synthesis, molecular docking and biological potentials of new 2-(4-(2-chloroacetyl) piperazin-1-yl)-N-(2-(4-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetamide derivatives

Mehta S, Kumar S, Marwaha RK, Narasimhan B, Ramasamy K, Lim SM, et al.

BMC Chem, 2019 Dec;13(1):113.
PMID: 31517312 DOI: 10.1186/s13065-019-0629-0

In the present study, a series of 2-(4-(2-chloroacetyl)piperazin-1-yl)-N-(2-(4-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetamide derivatives was synthesized and its chemical structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were evaluated for their in vitro antimicrobial (tube dilution technique) and anticancer (MTT assay) activities along with molecular docking study by Schrodinger 2018-1, maestro v11.5. The antimicrobial results indicated that compounds 3, 8, 11 and 12 displayed the significant antimicrobial activity and comparable to the standards drugs (ciprofloxacin and fluconazole). The anticancer activity results indicated that compound 5 have good anticancer activity among the synthesized compounds but lower active than the standard drugs (5-fluorouracil and tomudex). Molecular docking study demonstrated that compounds 5 and 7 displayed the good docking score with better anticancer potency within the binding pocket and these compounds may be used as a lead for rational drug designing for the anticancer molecules.
Fulltext Using Quantitative Polymerase Chain Reaction (qPCR) to Identify a Myriad of Carbapenemase Genes in Fresh Cow Dung in Bangladesh

Al Asad M, Siddique Shanta A, Akter K, Binte Habib M, Nahar S, Haque M, et al.

Cureus, 2024 Feb;16(2):e54644.
PMID: 38389567 DOI: 10.7759/cureus.54644

Introduction The emergence of antimicrobial resistance (AMR) is driven by the selection pressure of frequent uses of antimicrobial agents in healthcare, the food chain, agriculture, fishery, and the food animal industry, which poses a serious health risk for transmission-linked humans and the surrounding environment. Livestock, particularly cattle, play an essential role in the food sector in Bangladesh. The food-animal chains can be the potential routes of exposure to AMR-microorganisms for every domain of one health. Antimicrobial resistance genes (ARGs) can impart a reservoir of AMR within the food supply chain, even without pathogenic microorganisms. This study investigated the history of infection for the last six-month period of antimicrobials utilized in cattle farms and the distribution of selected carbapenemase resistance genes, namely, bla-KPC, bla-IMP, bla-VIM, bla-NDM-1, bla-SIM, bla-GIM, bla-SPM, and bla-SME, in cattle feces in Bangladesh. Methods A cross-sectional study was designed to analyze ARGs in fresh cow dung samples collected from commercial farms and individual houses in four Bangladesh districts, namely, Dhaka, Gazipur, Manikganj, and Tangail. Types of cattle breeds, their existing diseases, recent antimicrobial uses, and vaccine uses were recorded. DNA was extracted from each cow dung sample using commercial kits (Qiagen GmbH, Germany). Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the eight carbapenem resistance genes in the extracted DNA. The eight carbapenem resistance genes in the extracted DNA were assessed by RT-qPCR using the qTOWER3 thermal cycler (Analytik Jena GmbH, Konrad-Zuse-Straße 1, 07745 Jena, Germany). Results Group A carbapenemase, bla-KPC, was detected in 66.7% of the samples. However, no bla-SME was identified in all of the test samples. Group B metallo carbapenemase, bla-IMP, bla-NDM-1, bla-VIM, bla-SIM, bla-GIM, and bla-SPM, were in 66.7% (80/120), 49.2% (59/120), 48.3% (58/120), 68.3% (82/120), 58.3% (70/120), and 12.5% (15/120), respectively. Only 8.3% of the tested samples contained no MBL gene; 10% carried a single-type carbapenemase gene; and the remaining 81.7% carried two or more carbapenemase genes concurrently. Co-carriage of four or more genes was found in over 59% of samples. As many as seven genes were found together in 6.7% of samples. ARG detection in commercial cattle samples and household feces is not statistically significant. Conclusions Substantial carbapenem-resistance ARGs were detected in commercially farmed cow dung and household cattle samples. Frequent use of antibiotics for cattle for treatment and prophylactic purposes may influence the high acquisition of ARGs. Bangladeshi cattle farms are reservoirs and routes of AMR, posing a significant threat to the country's public health.
Fulltext Synthesis, molecular docking and biological evaluation of bis-pyrimidine Schiff base derivatives

Kumar S, Lim SM, Ramasamy K, Vasudevan M, Shah SAA, Selvaraj M, et al.

Chem Cent J, 2017 Sep 18;11(1):89.
PMID: 29086867 DOI: 10.1186/s13065-017-0322-0

BACKGROUND: Heterocyclic pyrimidine nucleus, which is an essential base component of the genetic material of deoxyribonucleic acid, demonstrated various biological activities. A series of bis-pyrimidine Schiff bases were synthesized and screened for its antimicrobial and anticancer potentials. The molecular docking study was carried to find the interaction between active molecules with receptor.
RESULTS: The structures of synthesized bis-pyrimidine Schiff bases were confirmed by spectral studies. The synthesized bis-pyrimidine derivatives were evaluated for their antimicrobial activity (MIC = µmol/mL) against selected Gram positive; Gram negative bacterial and fungal strains by tube dilution method. The anticancer activity (IC50 = µmol/mL) of the synthesized compounds was determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) assay. Molecular docking studies provided information regarding the binding mode of active bis-pyrimidine Schiff bases with the cyclin-dependent kinase 8 (CDK8) receptor.
CONCLUSIONS: The antimicrobial screening results indicated that compounds, q1 (MICbs = 0.83 µmol/mL), q16 (MICan = 1.54 µmol/mL and MICec = 0.77 µmol/mL), q1 and q19 (MICca = 0.41 µmol/mL) and q20 (MIC = 0.36 µmol/mL) are the most active ones. Compounds q1 (IC50 = 0.18 µmol/mL) have emerged as potent anticancer molecule against human colorectal carcinoma cancer cell line than the reference drug, 5-fluorouracil. Molecular docking studies indicated that compound q1 (the most active molecule) has the maximum hydrogen bond interaction (four) and π-π stacking (three) network among the bis-pyrimidine Schiff bases. Graphical abstract Graphical illustration of predicted binding mode of bis-pyrimidine Schiff bases in the active site of CDK8. a. Compound 1 (magenta color), b. Compound 5 (green color), c. Compound 8 (red color), d. Compound 13 (split pea color).
Effects of flavanols and procyanidins-rich cocoa consumption on metabolic syndrome: an update review (2013-2023)

Salaish Kumar S, Mhd Jalil AM, Hussin N, Mat Daud Z', Ismail A

Biosci Biotechnol Biochem, 2024 Mar 22;88(4):352-360.
PMID: 38285609 DOI: 10.1093/bbb/zbae011

Studies indicated that cocoa-based products effectively mitigate the risks associated with metabolic syndrome (MetS), however, the effect varies based on cocoa types, dosages, and study durations. This review aimed to determine the flavanol-rich cocoa consumption on MetS outcomes within the last decade (2013-2023), adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven randomized-controlled trials (RCTs) used cocoa-based products containing 0.3-1680 mg flavanol monomers and 3.5-1270 mg procyanidins. Cocoa-based products beneficially reduced glycemic response, blood pressure and lipid profiles. However, this review highlights little evidence pinpointing the best cocoa products type and required dosage for the observed effects. Further intervention aiming to improve MetS should justify the selection and concentration of flavanols (monomers and procyanidins). A robust study design should consider registering the trials before study commencement, consider multicenter RCT trials, and adjust for potential covariates that might "masked" the outcomes.
Fulltext Bis-pyrimidine acetamides: design, synthesis and biological evaluation

Kumar S, Lim SM, Ramasamy K, Vasudevan M, Shah SAA, Narasimhan B

Chem Cent J, 2017 Aug 08;11(1):80.
PMID: 29086907 DOI: 10.1186/s13065-017-0312-2

BACKGROUND: In the past few years, increased resistance of microorganisms towards antimicrobial agents become a serious health problem, so there is a need for the discovery of new antimicrobial agents. On the other hand, bis-pyrimidines possess various types of biological activity. In view of this, in the present study we have designed and synthesized a new series of bis-pyrimidine acetamides by Claisen-Schmidt condensation and screened for its in vitro antimicrobial and anticancer activities.
RESULTS: The synthesized bis-pyrimidine acetamide derivatives were confirmed by IR, (1)H/(13)C-NMR, Mass spectral studies as well C, H, N analyses. The synthesized compounds were evaluated for their in vitro antimicrobial potential against Gram positive (Staphylococcus aureus and Bacillus subtilis); Gram negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica) bacterial and fungal (Candida albicans and Aspergillus niger) strains by tube dilution technique and the minimum inhibitory concentration (MIC) recorded in µmol/mL was comparable to reference drugs, cefadroxil (antibacterial) and fluconazole (antifungal). The in vitro anticancer activity (IC50 value) determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) technique and 5-fluorouracil used as reference drug.
CONCLUSIONS: The biological study demonstrated that compounds 3, 13, 16, 17 and 18 were found to be most active antimicrobial agents with best MIC values than the cefadroxil (antibacterial) and fluconazole (antifungal) and compounds 12, 16 and 18 found to have better anticancer activity against human colorectal carcinoma (HCT116) cancer cell line with best IC50 value than the 5-fluorouracil (anticancer). Graphical abstract SAR of bis-pyrimidine acetamides.
Fulltext Suppression of Proinflammatory Cytokines and Mediators in LPS-Induced RAW 264.7 Macrophages by Stem Extract of Alternanthera sessilis via the Inhibition of the NF-κB Pathway

Muniandy K, Gothai S, Badran KMH, Suresh Kumar S, Esa NM, Arulselvan P

J Immunol Res, 2018;2018:3430684.
PMID: 30155492 DOI: 10.1155/2018/3430684

Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1β, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.
Fulltext Computational drug screening against the SARS-CoV-2 Saudi Arabia isolates through a multiple-sequence alignment approach

Mok PL, Koh AE, Farhana A, Alsrhani A, Alam MK, Suresh Kumar S

Saudi J Biol Sci, 2021 Apr;28(4):2502-2509.
PMID: 33551661 DOI: 10.1016/j.sjbs.2021.01.051

COVID-19 is a rapidly emerging infectious disease caused by the SARS-CoV-2 virus currently spreading throughout the world. To date, there are no specific drugs formulated for it, and researchers around the globe are racing against the clock to investigate potential drug candidates. The repurposing of existing drugs in the market represents an effective and economical strategy commonly utilized in such investigations. In this study, we used a multiple-sequence alignment approach for preliminary screening of commercially-available drugs on SARS-CoV sequences from the Kingdom of Saudi Arabia (KSA) isolates. The viral genomic sequences from KSA isolates were obtained from GISAID, an open access repository housing a wide variety of epidemic and pandemic virus data. A phylogenetic analysis of the present 164 sequences from the KSA provinces was carried out using the MEGA X software, which displayed high similarity (around 98%). The sequence was then analyzed using the VIGOR4 genome annotator to construct its genomic structure. Screening of existing drugs was carried out by mining data based on viral gene expressions from the ZINC database. A total of 73 hits were generated. The viral target orthologs were mapped to the SARS-CoV-2 KSA isolate sequence by multiple sequence alignment using CLUSTAL OMEGA, and a list of 29 orthologs with purchasable drug information was generated. The results showed that the SARS CoV replicase polyprotein 1a had the highest sequence similarity at 79.91%. Through ZINC data mining, tanshinones were found to have high binding affinities to this target. These compounds could be ideal candidates for SARS-CoV-2. Other matches ranged between 27 and 52%. The results of this study would serve as a significant endeavor towards drug discovery that would increase our chances of finding an effective treatment or prevention against COVID19.
Fulltext Human Mesenchymal Stem Cells Expressing Erythropoietin Enhance Survivability of Retinal Neurons Against Oxidative Stress: An In Vitro Study

Shirley Ding SL, Kumar S, Ali Khan MS, Ling Mok P

Front Cell Neurosci, 2018;12:190.
PMID: 30108483 DOI: 10.3389/fncel.2018.00190

Retinal degeneration is a prominent feature in ocular disorders. In exploring possible treatments, Mesenchymal Stem Cells (MSCs) have been recognized to yield therapeutic role for retinal degenerative diseases. Studies have also displayed that erythropoietin (EPO) administration into degenerative retina models confers significant neuroprotective actions in limiting pathological cell death. In this study, we aimed to use MSCs to deliver EPO and to evaluate the ability of EPO to rescue retinal neurons from dying upon reactive oxidative stress induction. We derived human MSCs from Wharton's jelly (hWJMSCs) of the umbilical cord and cells were transduced with lentivirus particles encoding EPO and a reporter gene of green fluorescent protein (GFP). The supernatants of both transduced and non-transduced cells were collected and used as a pre-conditioning medium for Y79 retinoblastoma cells (retinal neuron cell line) following exposure to glutamate induction. Retinal cells exposed to glutamate showed reduced mitochondrial depolarization and enhanced improvement in cell viability when incubated with pre-conditioned media of transduced cells. Our results established a proof-of-concept that MSCs could be used as a candidate for the delivery of EPO therapeutic gene in the treatment of retinal degenerations.
Fulltext Preventive Effect of Naringin on Metabolic Syndrome and Its Mechanism of Action: A Systematic Review

Raja Kumar S, Mohd Ramli ES, Abdul Nasir NA, Ismail NHM, Mohd Fahami NA

Evid Based Complement Alternat Med, 2019;2019:9752826.
PMID: 30854019 DOI: 10.1155/2019/9752826

Background: Metabolic syndrome (MetS), which consists of cluster of conditions, hypertension, hyperlipidemia, hyperglycemia, and visceral obesity, is affecting population worldwide. Studies have shown that plant derived flavonoids have the ability to alleviate MetS. Naringin is a type of glycoside flavonoid found in most plant and it plays a critical role in the treatment of MetS due to its antioxidant activity and ability to regulate cytokines.
Methods: A systematic review was done to study the effects of naringin on the metabolic diseases using electronic databases which include Ovid and Scopus using specific descriptors published from the year 2010 till present to provide updated literature on this field. The articles were assessed and chosen based on the criteria in which the mechanisms and effects of naringin on different metabolic diseases were reported.
Results: Thirty-four articles were identified which referred to the studies that correspond to the previously stated criteria. Subsequently after screening for the articles that were published after the year 2010, finally, 19 articles were selected and assessed accordingly. Based on the assessment, naringin could alleviate MetS by reducing visceral obesity, blood glucose, blood pressure, and lipid profile and regulating cytokines.
Conclusions: Naringin is an antioxidant that appears to be efficacious in alleviating MetS by preventing oxidative damage and proinflammatory cytokine release. However, the dosage used in animal studies might not be achieved in human trials. Thus, adequate investigation needs to be conducted to confirm naringin's effects on humans.

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