Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods.

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1-16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone's C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO-LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of - 8.5 kcal mol-1. This result outperformed the affinity of the reference standard dapagliflozin (- 7.9 kcal mol-1) as well as two other compounds that target human IDE, namely vitexin (- 8.3 kcal mol-1) and myricetin (- 8.4 kcal mol-1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein-ligand complex at the active site.

In Silico Discovery and Predictive Modeling of Novel Acetylcholinesterase (AChE) Inhibitors for Alzheimer's Treatment.

INTRODUCTION: Alzheimer's disease, akin to coronary artery disease of the heart, is a progressive brain disorder driven by nerve cell damage. METHOD: This study utilized computational methods to explore 14 anti-acetylcholinesterase (AChE) derivatives (1 ̶ 14) as potential treatments. By scrutinizing their interactions with 11 essential target proteins (AChE, Aß, BChE, GSK-3ß, MAO B, PDE-9, Prion, PSEN-1, sEH, Tau, and TDP-43) and comparing them with established drugs such as donepezil, galantamine, memantine, and rivastigmine, ligand 14 emerged as notable. During molecular dynamics simulations, the protein boasting the strongest bond with the critical 1QTI protein and exceeding drug-likeness criteria also exhibited remarkable stability within the enzyme's pocket across diverse temperatures (300 ̶ 320 K). In addition, we utilized density functional theory (DFT) to compute dipole moments and molecular orbital properties, including assessing the thermodynamic stability of AChE derivatives. RESULT: This finding suggests a welldefined, potentially therapeutic interaction further supported by theoretical and future in vitro and in vivo investigations. CONCLUSION: Ligand 14 thus emerges as a promising candidate in the fight against Alzheimer's disease.

Design, synthesis, and bioevaluation of novel unsaturated cyanoacetamide derivatives: In vitro and in silico exploration.

In this study, we synthesized novel α,ß-unsaturated 2-cyanoacetamide derivatives (1-5) using microwave-assisted Knoevenagel condensation. Characterization of these compounds was carried out using FTIR and 1H NMR spectroscopy. We then evaluated their in vitro antibacterial activity against both gram-positive and gram-negative pathogenic bacteria. Additionally, we employed in silico methods, including ADMET prediction and density functional theory (DFT) calculations of molecular orbital properties, to investigate these cyanoacetamide derivatives (1-5). Molecular docking was used to assess the binding interactions of these derivatives (1-5) with seven target proteins (5MM8, 4NZZ, 7FEQ, 5NIJ, ITM2, 6SE1, and 5GVZ) and compared them to the reference standard tyrphostin AG99. Notably, derivative 5 exhibited the most favorable binding affinity, with a binding energy of -7.7 kcal mol-1 when interacting with the staphylococcus aureus (PDB:5MM8), while also meeting all drug-likeness criteria. Additionally, molecular dynamics simulations were carried out to evaluate the stability of the interaction between the protein and ligand, utilizing parameters such as Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (Rg), and Principal Component Analysis (PCA). A 50 nanosecond molecular dynamics (MD) simulation was performed to investigate stability further, incorporating RMSD and RMSF analyses on compound 5 within the active binding site of the modeled protein across different temperatures (300, 305, 310, and 320 K). Among these temperatures, compound 5 exhibited an RMSD value ranging from approximately 0.2 to 0.3 nm at 310 K (body temperature) with the 5MM8 target, which differed from the other temperature conditions. The in silico results suggest that compound 5 maintained significant conformational stability throughout the 50 ns simulation period. It is consistent with its low docking energy and in vitro findings concerning α,ß-unsaturated cyanoacetamides. Key insights from this study include:•The creation of innovative α,ß-unsaturated 2-cyanoacetamide derivatives (1-5) employing cost-effective, licensed, versatile, and efficient software for both in silico and in vitro assessment of antibacterial activity.•Utilization of FTIR and NMR techniques for characterizing compounds 1-5.

Tolperisone hydrochloride improves motor functions in Parkinson's disease via MMP-9 inhibition and by downregulating p38 MAPK and ERK1/2 signaling cascade.

The mitogen-activated protein kinase (MAPK) signaling pathway, particularly the p38 MAPK and ERK1/2, has been implicated in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that MAPK signaling pathway can influence the expression of matrix metalloproteinase 9 (MMP-9), known for its involvement in various physiological and pathological processes, including neurodegenerative diseases. This study explores the modulation of MMP-9 expression via the MAPK/ERK signaling cascade and its potential therapeutic implications in the context of PD-associated motor dysfunction. Here, tolperisone hydrochloride (TL), a muscle relaxant that blocks voltage-gated sodium and calcium channels, was used as a treatment to observe its effect on MAPK signaling and MMP-9 expression. Rotenone (RT) exposure in mice resulted in a significant reduction in substantia nigra and primary motor cortex neurons, which were further evidenced by impairments in motor function. When TL was administered, neuron count was restored (89.0 ± 4.78 vs 117.0 ± 4.46/mm2), and most of the motor dysfunction was alleviated. Mechanistically, TL reduced the protein expression of phospho-p38MAPK (1.06 fold vs 1.00 fold) and phospho-ERK1/2 (1.16 fold vs 1.02 fold), leading to the inhibition of MAPK signaling, as well as reduced MMP-9 concentrations (2.76 ± 0.10 vs 1.94 ± 0.10 ng/mL) in the process of rescuing RT-induced neuronal cell death and motor dysfunction. Computational analysis further revealed TL's potential inhibitory properties against MMP-9 along with N and L-type calcium channels. These findings shed light on TL's neuroprotective effects via MMP-9 inhibition and MAPK signaling downregulation, offering potential therapeutic avenues for PD-associated motor dysfunction.

Exploring the anticancer and antibacterial potential of naphthoquinone derivatives: a comprehensive computational investigation.

This study investigates the potential of 2-(4-butylbenzyl)-3-hydroxynaphthalene-1,4-dione (11) and its 12 derivatives as anticancer and biofilm formation inhibitors for methicillin-resistant staphylococcus aureus using in silico methods. The study employed various computational methods, including molecular dynamics simulation molecular docking, density functional theory, and global chemical descriptors, to evaluate the interactions between the compounds and the target proteins. The docking results revealed that compounds 9, 11, 13, and ofloxacin exhibited binding affinities of -7.6, -7.9, -7.5, and -7.8 kcal mol-1, respectively, against peptide methionine sulfoxide reductase msrA/msrB (PDB: 3E0M). Ligand (11) showed better inhibition for methicillin-resistant staphylococcus aureus msrA/msrB enzyme. The complex of the 3E0M-ligand 11 remained highly stable across all tested temperatures (300, 305, 310, and 320 K). Principal Component Analysis (PCA) was employed to evaluate the behavior of the complex at various temperatures (300, 305, 310, and 320 K), demonstrating a total variance of 85%. Convergence was confirmed by the eigenvector's cosine content value of 0.43, consistently displaying low RMSD values, with the minimum observed at 310 K. Furthermore, ligand 11 emerges as the most promising candidate among the compounds examined, showcasing notable potential when considering a combination of in vitro, in vivo, and now in silico data. While the naphthoquinone derivative (11) remains the primary candidate based on comprehensive in silico studies, further analysis using Frontier molecular orbital (FMO) suggests while the Egap value of compound 11 (2.980 eV) and compound 13 (2.975 eV) is lower than ofloxacin (4.369 eV), indicating their potential, so it can be a statement that compound 13 can also be investigated in further research.

New record of Philometra species from the marine edible fish Terapon jarbua collected from the Sindh, Arabian Sea, Pakistan.

Diseases in fish due to helminth parasites, especially Philometra species, are the primary worry in aquaculture. Philometra are responsible for health problem in fishes they directly affect fish growth and population parameters. A comprehensive survey was conducted involving the examination of the marine fish species Terapon jarbua, gathered from the coastal waters of Sindh, Pakistan In this research different Philometra species from marine fish Terapon jarbua during 2021 and 2022. Philometra nematodes, belonging to the family Philometridae, are common parasitic organisms inhabiting both marine and freshwater environments. Their prevalence, particularly when existing in high numbers within host organisms, can lead to severe and potentially lethal consequences. Employing light microscopy techniques, diverse species of Philometra were identified, including Philometra teraponi, P. jarbuai, P. arabiai, P. karachii, and P. awarii, localized primarily within the ovaries of the host fish. A total of 140 fish samples were examined and 76 were infected. The intensity of infected fish was 54.28%. The identification process encompassed meticulous analysis of crucial parameters, such as body size, esophagus length, positioning of the nerve ring, dimensions of the ventriculus, and ligament size. Intriguingly, the parasites were found in varying contexts; while some were free within the ovaries, others were embedded within tissues, inducing severe muscular dystrophy. This research presents novel findings of Philometra nematodes in the marine waters of Pakistan, extending their host and geographical distribution records. Future studies are needed to better evaluate and describe the dynamics and the epidemiology of Philometra infection in wild and cultured fish species.

Exploring the effectiveness of flavone derivatives for treating liver diseases: Utilizing DFT, molecular docking, and molecular dynamics techniques.

In exploring nature's potential in addressing liver-related conditions, this study investigates the therapeutic capabilities of flavonoids. Utilizing in silico methodologies, we focus on flavone and its analogs (1-14) to assess their therapeutic potential in treating liver diseases. Molecular change calculations using density functional theory (DFT) were conducted on these compounds, accompanied by an evaluation of each analog's physiochemical and biochemical properties. The study further assesses these flavonoids' binding effectiveness and locations through molecular docking studies against six target proteins associated with human cancer. Tropoflavin and taxifolin served as reference drugs. The structurally modified flavone analogs (1-14) displayed a broad range of binding affinities, ranging from -7.0 to -9.4 kcal mol⁻¹, surpassing the reference drugs. Notably, flavonoid (7) exhibited significantly higher binding affinities with proteins Nrf2 (PDB:1 × 2 J) and DCK (PDB:1 × 2 J) (-9.4 and -8.1 kcal mol⁻¹) compared to tropoflavin (-9.3 and -8.0 kcal mol⁻¹) and taxifolin (-9.4 and -7.1 kcal mol⁻¹), respectively. Molecular dynamics (MD) simulations revealed that the docked complexes had a root mean square deviation (RMSD) value ranging from 0.05 to 0.2 nm and a root mean square fluctuation (RMSF) value between 0.35 and 1.3 nm during perturbation. The study concludes that 5,7-dihydroxyflavone (7) shows substantial promise as a potential therapeutic agent for liver-related conditions. However, further validation through in vitro and in vivo studies is necessary. Key insights from this study include:•Screening of flavanols and their derivatives to determine pharmacological and bioactive properties using ADMET, molinspiration, and pass prediction analysis.•Docking of shortlisted flavone derivatives with proteins having essential functions.•Analysis of the best protein-flavonoid docked complexes using molecular dynamics simulation to determine the flavonoid's efficiency and stability within a system.

Insights into the consequence of (Al-Zn) dual-doping on structural, morphological, and optoelectrical properties of CdO thin films.

The present study explores the structural, morphological, optical, and electrical properties of spray pyrolyzed (Al-Zn) dual-doped CdO thin films. The un-doped and (Al-Zn) dual-doped CdO thin films have been deposited on glass substrate using spray pyrolysis route at 325 °C. The physical properties of the doped samples were analyzed as a function of Zn concentration (2-5 mol%) with constant Al (3 mol%) concentration. XRD analysis confirms the successful incorporation of (Al-Zn) dual-doping into CdO crystal as well as the polycrystalline nature was evident. No phase transitions were apparent from XRD data while revealing the single cubic structure of all the samples. The surface morphology of the samples studied by SEM. It shows the formation of rock-shaped microstructure and the variation of grain size with doping concentrations. Optical analysis was done using UV-vis spectroscopy within the range of 300-1200 nm. Maximum value of transmittance was attained for 3% (Zn-Al)-doped CdO sample. The dual doping exhibits the broadening of band gap values (2.61-3.84 eV) whereas a decrease in extinction coefficient was noticed as a function of Zn doping concentration. Electrical analysis was done using the four-probe method and a high resistivity was seen for higher Zn concentration. Obtained results and precise comparison with some similar films suggested that 2% Zn and 3% Al co-doping can be a suitable candidate for optoelectronic devices.

Whole genome sequence of denitrifying bacterium Stutzerimonas stutzeri strain NGHE31, collected from an eutrophic wetland in Sunamganj, Bangladesh, following the 2017 flash floods.

Here, we report the whole genome sequence of Stutzerimonas stutzeri strain NGHE31, isolated from Dekhar Haor, following the 2017 flash flood that resulted in mass die-offs of local wildlife. The predicted genome size is 4,434,670 bp, with 63.97% GC content, 4,035 coding sequences, 3 rRNAs, and 50 tRNAs.

Saccharomyces cerevisiae survival against heat stress entails a communication between CCT and cell wall integrity pathway.

The chaperonin TRiC/CCT is cytosolic cylindrical complex of 16 subunits encoded by eight essential genes CCT1-8. It contributes to folding 10% of cellular polypeptides in yeast. The strain carrying substitution point mutation G412E in the equatorial domain of Cct7p resulted in the improper folding of substrates. In this study, the Cct7p mutant exhibited sensitivity to non-optimal growth temperatures and cell wall stressors. Heat shock is known to disrupt cell wall and protein stability in budding yeast. Mitogen-activated protein kinase-mediated cell wall integrity pathway gets activated to compensate the perturbed cell wall. Overexpression of the PKC1 and SLT2 genes of MAPK signaling pathway in mutant rescued the growth and cell division defects. Additionally, the genes of the CWI pathway such as SED1, GFA1, PIR1, and RIM21 are down-regulated. The Cct7p mutant strain (G412E) is unable to withstand the heat stress due to the underlying defects in protein folding and cell wall maintenance. Taken together, our results strongly indicate the interaction between CCT and cell wall integrity pathway.

Heavy Metals Accumulation in Vegetables and Its Consequences on Human Health in the Areas Influenced by Industrial Activities.

The degradation of the environment due to numerous industrial practices has emerged as a major issue globally, particularly in a country like Bangladesh. The present study dispenses information about heavy metal (Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb) contamination in some frequently consumed vegetables, namely, ash pumpkin, potato, bitter gourd, buffalo spinach, snake gourd, and pointed gourd grown in an industrially prone location and their repercussion on consumers' health. Proton-induced X-ray emission (PIXE) technique was used as the major analytical tool to detect heavy metal concentrations. Mean concentration and the range of Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb in vegetables were detected (4.81 ± 2.79, 2.43-10.94), (497.57 ± 258.08, 181.24-886.67), (644.49 ± 298.40, 179.56-998.78), (38.88 ± 14.31, 18.88-60.12), (58.11 ± 12.58, 42.55-84.79), (137.24 ± 48.37, 71.99-208.98), (123.31 ± 63.62, 49.97-256.09), (8.09 ± 2.69, 4.29-14.94), and (4.16 ± 2.95, 1.22-9.98) mg/kg (dry weight basis), respectively. An extreme level of heavy metal contamination in vegetable samples was notified regarding the estimated metal pollution index (MPI) and Nemerow pollution index (P) value, which underpinned the health risk values. The estimated hazard index (HI) value stipulated high risk in all varieties of vegetables regardless of age group and cadmium (Cd) was found as the major contributor. Concerning the carcinogenic risk index (CR) for single elements, the value of Co, Ni, and Cr was approximated far above the USEPA threshold risk limit (CR>1E-04). Moreover, total carcinogenic risk (TCR) for all varieties of vegetables exceeded the safety threshold value for both the age group and children, in particular, were found most vulnerable. The outshot of the present study divulged associated health risks for the population group by the heavy metals via dietary intake of vegetables.

Thyroid Hormone Level in Children with Nephrotic Syndrome.

Nephrotic syndrome is the most common glomerular disease affecting children. Hypothyroidism is one of the most important complications which occur due to urinary loss of protein bound thyroid hormones, such as thyroxin binding globulin, transthyretin and albumin. This cross sectional study was conducted in the Department of Pediatric, Mymensingh Medical College Hospital (MMCH), Bangladesh from February 2018 to October 2019. This study was carried out to find out the thyroid profile in children with nephrotic syndrome and compared with thyroid profile of other acute illness in children. Total 122 children aged 2-12 years, further subdivided into Group A (n=61) suffering from nephrotic syndrome (1st attack, infrequent relapse) and Group B (n=61) other disease like viral fever, pneumonia, bronchiolitis, diarrhoea, UTI. Demographic details of patients and their relevant clinical details were obtained by an interviewer administered questionnaire. Blood for free T4, TSH were taken and compared between both groups. The mean FT4 values in Group A and Group B were 16.09±22.32fmol/ml and 68.22±11.65fmol/ml respectively, whereas the TSH level was significantly higher in Group A than controls (5.42±1.04 vs. 3.53±1.44). The T4 levels in nephrotic syndrome (Group A) patients were low. Analysis was done by using SPSS 22.0 version for windows software. Continuous and catagorical parameters were compared by unpaired 't' test and Chi-Square test. A p-value of 0.05 was considered significant. Hypothyroidism was found more in younger children i.e. age less than 6 years. This study concluded that children with nephrotic syndrome have a state of hypothyroidism.

Early Inflammatory Response of Dental Pulp in Response to Biodentin and Mineral Trioxide Aggregate as Pulp-capping Agents.

This study was carried out to observe immediate inflammatory response of Human Dental Pulp capped with Biodentin and Mineral Trioxide Aggregate (MTA). This prospective clinical study was carried out in the Department of Conservative Dentistry and Endodontics together with the Department of Orthodontia, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from 2016 to 2018. A total number of eighty (80) permanent premolars teeth planned to be extracted for orthodontic alignment of occlusion were used as study sample. Those teeth were divided into two groups; Group A and Group B, having 40 teeth in each (n=40). An occlusal exposure of approximately 1.5mm in diameter was made. Then in -group A, exposed pulp were capped with 2-mm-thick layer of sterile Biodentin (Septodont) and in-group B with ProRoot White MTA (Dentsply). After pulp capping with the experimental material in respective group, cavities in all teeth were restored with glass ionomer cement. After 24 hours the teeth were extracted, fixed in 10% buffered formalin solution, then decalcified by 10.0% nitric acid and embedded in paraffin. Now 2 to 3-micron-thick serial sections were made in the linguo-buccal plane and finally stained with hematoxylin-eosin. Now pulpal inflammation in respect of type, intensity and extension, were determined by using a predetermined evaluation criterion under an optical microscope at 40× magnifications. Statistical differences among the experimental groups were analyzed by Descriptive analysis (Cross Tabulation) (p<0.05). Histologically both the tested materials produced immediate pulpal tissue reaction. 'Biodentin' found to be most immediate pulpal tissue reactive (reactive in 100% cases), Whereas, MTA produced immediate tissue reaction only in 50.0% cases. Immediate pulpal inflammatory reaction in response to tested material found to be statistically significant different between 'Biodentin' and 'MTA' (p=0.001). According to present study Biodentin is found to be more immediate pulpal tissue reactive than MTA when used as a pulp capping material.

Altered expression, but small contribution, of the histone demethylase KDM6A in obstructive uropathy in mice.

Epigenetic processes have emerged as important modulators of kidney health and disease. Here, we studied the role of KDM6A (a histone demethylase that escapes X-chromosome inactivation) in kidney tubule epithelial cells. We initially observed an increase in tubule cell Kdm6a mRNA in male mice with unilateral ureteral obstruction (UUO). However, tubule cell knockout of KDM6A had relatively minor consequences, characterized by a small reduction in apoptosis, increase in inflammation and downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In proximal tubule lineage HK-2 cells, KDM6A knockdown decreased PPARγ coactivator-1α (PGC-1α) protein levels and mRNA levels of the encoding gene, PPARGC1A. Tubule cell Kdm6a mRNA levels were approximately 2-fold higher in female mice than in male mice, both under sham and UUO conditions. However, kidney fibrosis after UUO was similar in both sexes. The findings demonstrate Kdm6a to be a dynamically regulated gene in the kidney tubule, varying in expression levels by sex and in response to injury. Despite the context-dependent variation in Kdm6a expression, knockout of tubule cell KDM6A has subtle (albeit non-negligible) effects in the adult kidney, at least in males.

Landscape structure influences natural pest suppression in a rice agroecosystem.

Agricultural landscapes are constantly changing as farmers adopt new production practices and respond to changing environmental conditions. Some of these changes alter landscape structure with impacts on natural pest control, pesticide use, and conservation of biodiversity. In rice agroecosystems the effect of landscape structure on natural enemies and pest suppression is often poorly understood. Here we investigate the effect of landscape composition and configuration on a key pest of rice, the brown planthopper (Nilaparvata lugens). Using N. lugens as sentinel prey coupled with predator exclusions, we investigated landscape effects on herbivore suppression and rice grain yield at multiple spatial scales in two regions of Bangladesh. Ladybird beetles and spiders were the most abundant natural enemies of N. lugens with landscape effects observed at all scales on ladybird beetles. Specifically, ladybird beetles were positively influenced by road edges, and fallow land, while spiders were strongly influenced only by rice phenology. Predator exclusion cages showed that N. lugens abundance significantly increased in caged plots, reducing rice gain yield. We also used an estimated biocontrol service index that showed a significant positive relationship with landscape diversity and a significant negative impact on pest density and yield loss. These results suggest that promoting fallow lands and fragmented patches between rice fields could lead to more sustainable insect pest management in rice agroecosystems, potentially reducing the practice of prophylactic insecticide use.

Role of White Blood Cell Count, Immature to Total Ratio and C-Reactive Protein in Early Detection of Clinically Suspected Neonatal Sepsis.

Despite recent advances in neonatal care, early detection of neonatal sepsis still remains challenging. Positive blood culture is the gold standard for definitive diagnosis of neonatal sepsis but is time consuming and demands a well equipped laboratory setting. Therefore, it becomes imperative to evaluate usefulness of white blood cell count, Immature to total (IT) ratio and C-reactive protein as potential markers in the early diagnosis of neonatal sepsis. The objective of the study was to evaluate role of white blood cell count, IT ratio and C-reactive protein in early detection of clinically suspected neonatal sepsis. This cross-sectional descriptive study was conducted from January 2017 to December 2018 at Special Care Newborn Unit (SCANU) of Rangpur Medical College Hospital, Rangpur, Bangladesh. After parental permission and ethical clearance, a total of 70 eligible neonates were included into the study. Estimation of total white blood cell count, IT ratio and C-reactive protein as well as blood culture were done for each case. Significance for Chi-Square test and Pearson's correlation coefficient test was predetermined as p<0.05. Of the total 70 neonates studied, 19(27.14%) were blood culture positive and most common organism was Escherichia coli (7/14, 37.0%). Among individual and combination tests, CRP was highly sensitive (100%) followed by WBC count (74.94%). Highly specific tests in diagnosing sepsis were combination test of IT ratio and CRP (88.23%) followed by combination test of WBC count and CRP (82.35%). Positive predictive value (PPV) was high for combination test of WBC count and CRP (90.90%) followed by combination test of IT ratio and CRP (90.47%). Negative predictive value (NPV) was high in CRP (100.0%) followed by WBC count (89.19%). IT ratio positively correlated with CRP (p=0.002) and there was significant association between raised CRP and WBC count (p=0.005) in neonatal sepsis. Diagnostic role of both individual and combination tests were significant in early detection of clinically suspected neonatal sepsis while awaiting results of blood culture. However, none of the combination tests were able to achieve 100.0% sensitivity.

Study on Myocardial Infarction in Young Adults: Risk Factor Analysis.

Coronary heart disease (CHD) imposes a significant burden on health care systems because of high morbidity and mortality. There is documented evidence that South Asian people develop CHD at a higher rate and at an early age. If the affected individual is 40 years old or below, the tragic consequences are catastrophic. Identifying risk factors could be important for health promotion. The objectives of this study were to determine the frequency of risk factors in young patients with acute myocardial infarction and thus with ischemic heart disease (IHD) aged 40 years and below in our population. It was a descriptive observational study which was carried out at Coronary Care Unit of Rajshahi Medical college Hospital, Rajshahi, Bangladesh in 61 patients from January 2011 to June 2011. All patients who fulfilled the inclusion criteria admitted to coronary care unit (CCU) with a diagnosis of Acute MI were included. Their detailed history was then taken including symptoms at presentation and their risk factors were assessed according to the Framingham Risk Scoring System with the help of history and laboratory investigations. Mean age ±SD of the patients was 36±3.7 year. Most of the patients were male. Smoking was the major risk factor (73.8%) followed by family history of IHD (44.3%). Other risk factors were dyslipidaemia (39.35%), hypertension (37.7%), obesity (11.5%) and diabetes mellitus (8.2%). Majority of the patients were adopted in sedentary lifestyle. 91.8% patient presented with chest pain. Other symptoms were dyspnoea (37.7%), palpitation (59.0%), sweating (77.0%), nausea, vomiting (50.8%) and impaired consciousness (19.7%) etc. Most frequent risk factor for acute myocardial infarction (MI) at young age is smoking followed by family history of MI and dyslipidaemia. Majority of the patients had two or more than two identifiable antecedent risk factors.

Synthesis of New Derivatives of Benzylidinemalononitrile and Ethyl 2-Cyano-3-phenylacrylate: In Silico Anticancer Evaluation.

In this study, microwave-assisted Knoevenagel condensation was used to produce two novel series of derivatives (1-6) from benzylidenemalononitrile and ethyl 2-cyano-3-phenylacrylate. The synthesized compounds were characterized using Fourier transform infrared (FT-IR) and 1H NMR spectroscopies. The pharmacodynamics, toxicity profiles, and biological activities of the compounds were evaluated through an in silico study using prediction of activity spectra for substances (PASS) and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies. According to the PASS prediction results, compounds 1-6 showed greater antineoplastic potency for breast cancer than other types of cancer. Molecular docking was employed to investigate the binding mode and interaction sites of the derivatives (1-6) with three human cancer targets (HER2, EGFR, and human FPPS), and the protein-ligand interactions of these derivatives were compared to those reference standards Tyrphostin 1 (AG9) and Tyrphostin 23 (A23). Compound 3 showed a stronger effect on two cell lines (HER2 and FPPS) than the reference drugs. A 20 ns molecular dynamics (MD) simulation was also conducted to examine the ligand's behavior at the active binding site of the modeled protein, utilizing the lowest docking energy obtained from the molecular docking study. Enthalpies (ΔH), Gibbs free energies (ΔG), entropies (ΔS), and frontier molecular orbital parameters (highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap, hardness, and softness) were calculated to confirm the thermodynamic stability of all derivatives. The consistent results obtained from the in silico studies suggest that compound 3 has potential as a new anticancer and antiparasitic drug. Further research is required to validate its efficacy.

Combined application of EPANET and empirical model for possible formation of trihalomethanes in water distribution network of Chattogram city to identify potential carcinogenic health risk zone.

The study identifies potential carcinogenic health risk-zone of Chattogram city for the occurrence of trihalomethanes (THMs) at its water distribution network. The EPANET-THMs simulation model along with an empirical model have been adopted in the study to predict THMs content of supply water of the distribution network of the city's Karnaphuli service area. The empirical model has estimated THMs level of supply water based on influential water quality parameters, and few of these have been used as pre-set values for subsequent EPANET simulation. The simulation (R2= 0.7) shows that THMs' concentrations throughout the network vary from 33 to 486 µg/L. Around 60% of total junctions showed THMs concentrations above 150 µg/L, while that is above 50 µg/L for most (99%) of the junctions. Residual Free chlorine, one of the precursors for the THMs formation in distribution line, has also been simulated by EPANET considering varying applied chlorine dose at the water purification unit and wall (Kw) and bulk (Kb) decay constants. The simulated free residual chlorine peaks are found to be closer to the actual values with chlorine dose of 2 mg/L, and decay constants, Kw = 1 d-1 and Kb = 1 d-1. A mean lifetime total risk of cancer due to the presence of THMs has been found to be very high. Spatial distribution of carcinogenic risk shows that the central zone of the service area is the most vulnerable zone, followed by the western and northern zone. The first ever zone wise risk identification could be used as baseline data for operational and regulatory purposes and may raise awareness among the city's inhabitants. Furthermore, the application of EPANET in combination with an empirical model could be an effective tool for predicting THMs' concentration in water distribution networks in developing countries like Bangladesh to minimize the expenses of measuring THMs.

Single cell G-protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21.

BACKGROUND AND PURPOSE: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G-protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. EXPERIMENTAL APPROACH: RNA sequencing and single cell qRT-PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue. KEY RESULTS: Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α-smooth muscle actin (α-SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin-angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty-six GPCRs were up-regulated in single Tcf21+ kidney fibroblasts, the most up-regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up-regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α-SMA+ interstitial cells in human kidney samples. CONCLUSION AND IMPLICATIONS: Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.