Association of Low Serum Free Testosterone with Carotid Atherosclerosis in Male.

The cross sectional descriptive type of observational study was aimed to evaluate the association of serum free testosterone in 59 patients of carotid atherosclerotic male {<50% stenosis (n=26); >50% stenosis (n=33) } from March 2015 to February 2016 in the Department of Radiology & Imaging of Bangabandhu Sheikh Mujib Medical University (BSMMU) & National Institute of Neurosciences (NINS), Dhaka, Bangladesh. Twenty seven patients who had normal carotid doppler findings were taken as control. Serum total testosterone and sex hormone binding globulin was measured by chemiluminescence micro particle immunoassay and free testosterone was done by using Vermeulen formula. Concentration of free testosterone differed significantly among groups (p=0.004) and it was significantly lower in <50% stenosed group. Logistic regression analysis revealed that low free testosterone (free testosterone ≤0.24 nmol/L) was independently associated with development of carotid atherosclerosis (p=0.04, OR 3.07, 95% CI 1.14-9.30). In conclusion low serum free testosterone was associated with carotid atherosclerosis in male.

Level of Serum Vitamin D, To Which People Are at Risk of Developing Acute Myocardial Infarction in Bangladesh.

Incidence of Myocardial Infarction is increasing day by day in developing countries. Most of the patients who sustain myocardial infarction have coronary atherosclerosis. There are several risk factors for the development of atherosclerosis. Among all the risk factors, vitamin D deficiency has been proposed to play an important role in the development of atherosclerosis. With this aim, a case-control study was carried out to explore the association of serum vitamin D with acute myocardial infarction. The enrolled study subjects were categorized into Group A which comprised of STEMI, Group B, comprised of NSTEMI and Group C comprised of age and sex matched individuals free from acute myocardial infarction. The mean values of serum vitamin D (in ng/ml) were 20.17, 20.8 and 24.77 respectively in STEMI, NSTEMI and control groups. It differed significantly among groups (p<0.001) and it was significantly low in STEMI and NSTEMI groups compared to control group (p<0.001 and p=0.004). From this study it can be concluded that low serum vitamin D is an independent risk factor for developing acute myocardial infarction. Individuals with serum vitamin D <20ng/ml have higher chance of developing acute myocardial infarction compared to those with serum vitamin D >20ng/ml.

Mental Health of the COVID-19 Patients in Bangladesh.

The mental health aspect of coronavirus disease-19 (COVID-19) patients in Bangladesh has remained less focused and has not been addressed properly. The objective of the study was to assess the levels of anxiety and depression in COVID-19 patients. We adopted a mixed online and telephone-based survey using Google Forms. Recruitment was performed through a snowball sampling approach. The Google Form was initially circulated in Facebook to identify interested participants. Then, three trained physicians interviewed the online responders over telephone for a period spanning from April 2020 to June 2020. Two well-known questionnaires, the Generalized Anxiety Disorder 7-item (GAD-7) scale and the Patient Health Questionnaire (PHQ-9), were used for the assessment of anxiety and depression, respectively. Here, the severity of anxiety was classified with the standard thresholds: minimal or none (0-4), mild (5-9), moderate (10-14) and severe (>15) for the GAD-7. Depression severity score: 0-4 was considered as none or no depression, 5-9: mild, 10-14: moderate, 15-19: moderately severe, 20-27 was for severe depression. A total of 237 patients were finally analyzed. The mean age ±SD of the patients was 41.59±13.73 years. Most of them were male (73%) and lived in urban areas (90.29%). Half of the patients were unemployed, and 17.7% admitted loss of job due to lockdown. The overall prevalence of anxiety and depression was 55.7% and 87.3%, respectively. The mean GAD-7 score was 5.79±4.95, and the mean PHQ-9 score was 5.64±5.15. Among the depressive patients, 3% had minimal depression, 38.4% had mild depression, 32.1% had moderate depression, 11.8% had moderate depression, and 2.1% had a severe depression. Similarly, 37.1%, 10.5% and 8% had mild, moderate and severe levels of anxiety, respectively. Nearly half of the study population (47.7%) was suffering from both depression and anxiety. Living in urban area was an independent predictor for depression (OR 3.882; CI: 1.249-12.069). Considering the high comorbid burden, the mental health issues of these patients need to be addressed and reinforced to the existing health system on a priority basis.

Expansion of a novel lead targeting M. tuberculosis DHFR as antitubercular agents.

A series of 1-(1-benzyl-2-methyl-5-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)-1H-indol-3-yl)ethanone and ethyl 1-benzyl-2-methyl-5-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)-1H-indole-3-carboxylate derivatives were designed based on bioisosteric replacement of previously reported antitubercular agent (IND-07). Twenty ligands were successfully synthesized and some of them were found to have good in vitro activity (MIC < 10 µM) against the H37Rv strain of Mycobacterium tuberculosis. Among these compounds, KC-08 and KC-11 inhibited Mtb-DHFR with 4- and 18-fold selectivity for Mtb-DHFR over h-DHFR, respectively. Compound KC-11 display acceptable ADME, and better pharmacokinetic profiles than IND-07. Docking studies were performed to predict the binding mode of the compounds within the active site of Mtb-DHFR and h-DHFR. The results of our study suggest that compound KC-11 may serve as a valuable lead for the design and development of selective inhibitors of Mtb-DHFR with potential therapeutic application in tuberculosis.

Structural comparison of Mtb-DHFR and h-DHFR for design, synthesis and evaluation of selective non-pteridine analogues as antitubercular agents.

Tuberculosis is an infectious disease that affects millions of population every year. Mtb-DHFR is a validated target that is vital for nucleic acids biosynthesis and therefore DNA formation and cell replication. This paper report identification and synthesis of novel compounds for selective inhibition of Mtb-DHFR and unleash the selective structural features necessary to inhibit the same. Virtual screening of databases was carried out to identify novel compounds on the basis of difference between the binding pockets of the two proteins. Consensus docking was performed to improve upon the results and best ten hits were selected. Hit 1 was subjected to analogues design and the analogues were docked against Mtb-DHFR. From the docking results 11 compounds were selected for synthesis and biological assay against H37Rv. Most potent compound (IND-07) was tested for selectivity using enzymatic assay against Mtb-DHFR and h-DHFR. The compounds were found to have good inhibitory activity (25-200 µM) against H37Rv and in enzyme assay against Mtb-DHFR and h-DHFR the compound was found selective towards Mtb-DHFR with selectivity index of 6.53. This work helped to identify indole moiety as novel scaffold for development of novel selective Mtb-DHFR inhibitors as antimycobacterial agents.

Quinoline based furanones and their nitrogen analogues: Docking, synthesis and biological evaluation.

A small library of twenty-four quinoline based butenolides also known as furanones and their nitrogen analogues was prepared by using two different aroylpropionic acids, viz. 3-(2-naphthoyl)propionic acid (3) and 3-(biphenyl-4-yl)propionic acid (4), as starting materials. The 3-aroylpropionic acids were reacted with different 6-substituted-2-chloroquinolin-3-carbaldehydes (2a-d) to obtain the corresponding furan-2(3H)-ones (5a-h). The purified and characterized furanones were then converted into their corresponding 2(3H)-pyrrolones (6a-h) and N-benzyl-pyrrol-2(3H)-ones (7a-h). The antimicrobial activities of the title compounds were evaluated against two strains of each Gram +ve (Staphylococcus aureus and Bacillus subtilis), Gram -ve bacteria (Escherichia coli and Pseudomonas aeruginosa) and against fungal strains of Aspergillus niger and Aspergillus flavus. In vivo anti-inflammatory potential of the title compounds was investigated by standard method. Majority of the compounds showed significant antibacterial activity against both the Gram +ve strains. Eight most potent anti-inflammatory compounds (5b, 5d, 5h, 6b, 7b, 7d, 7f, 7h) which exhibited >53% inhibition in edema, were also screened for their in vivo analgesic activity. All the tested compounds were found to have significant reduction in ulcerogenic action but only three compounds (5d, 5h and 7h) showed comparable analgesic activity to standard drug, diclofenac. The results were also validated using in silico approach and maximum mol doc score was obtained for compounds 7a-h. On comparing the in vivo and in silico anti-inflammatory results of synthesized compounds, N-benzyl pyrrolones (7a-h) emerged as the potent anti-inflammatory agents. It was also observed that compounds that possess electron withdrawing group such as -Cl or NO2 are more biologically active.

Pharmacophore based virtual screening, synthesis and SAR of novel inhibitors of Mycobacterium sulfotransferase.

A planned 3D-pharmacophore mapping was carried out on the basis of chemical features associated with known Stf0 inhibitors. Four models (model 1-4) were obtained after GASP (Genetic Algorithm Similarity Program) refinement of seven models (D-1 to D-7) generated by using DISCOtech. The selected GASP model-1 has two hydrogen bond acceptor, two hydrogen bond donor and four hydrophobic points. This model was used for virtual screening (VS) of large public databases along with in house generated knowledge base database. VS followed by docking of selected compounds on Stf0 active site was carried and pose analysis done. Seven hits were identified after all the computational studies, of which 2 hits were synthesized along with their analogs and evaluated for antitubercular activity. IH-45 was found promising after in vitro assay.

Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents.

A series of benzfused heterocyclic derivatives such as amide conjugates of 2-(benzo[d]thiazol-2-ylthio)acetic acid with aromatic/aliphatic/cyclic secondary amines (5a-5o & 8a-8m); 1,2,3-triazole conjugates of 2-mercaptobenzothiazoles and amide conjugates of indole-3-glyoxalic acid with cyclic secondary amines (14a-14g) have been synthesized and were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. Compounds 8b, 8f, 8g and 8l inhibited the growth of the H37Rv strain at concentrations of 8 µg/mL. These compounds (8b, 8f, 8g and 8l) have been further identified as bactericidal and are completely killing the microbes at 32-64 µg/mL concentrations. Molecular docking studies of the active compounds reveal that these compounds are targeting DprE1 and may act as DprE1 inhibitors.

Synthesis and biological evaluation of 2,5-disubstituted 1,3,4-oxadiazole derivatives with both COX and LOX inhibitory activity.

Dual cyclooxygenase/lipoxygenase (COX/LOX) inhibitors constitute a valuable alternative to classical nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors for the treatment of inflammatory diseases. A series of 3-(5-phenyl/phenylamino-[1,3,4]oxadiazol-2-yl)-chromen-2-one and N-[5-(2-oxo-2H-chromen-3-yl)-[1,3,4]oxadiazol-2-yl]-benzamide derivatives were synthesized and screened for anti-inflammatory, analgesic activity. All the derivatives prepared are active in inhibiting oedema induced by carrageenan. Compound 4e was found more potent with 89% of inhibition followed by compound 4b (86%). Compounds with >70% of anti-inflammatory activity were tested for analgesic, ulcerogenic, and lipid peroxidation profile. Selected compounds were also evaluated for inhibition of COXs (COX-1 and COX-2) and LOXs (LOX-5, LOX-12, and LOX-15). Compound 4e was comparatively selective for COX-2, LOX-5, and LOX-15. Study revealed that these derivatives were more effective than ibuprofen with reduced side effects. It can be suggested that these derivatives could be used to develop more potent and safer NSAIDs.

Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma.

BACKGROUND: The purpose of this study was to identify new tumour suppressor microRNAs (miRs) in clear cell renal cell carcinoma (ccRCC), carry out functional analysis of their suppressive role and identify their specific target genes. METHODS: To explore suppressor miRs in RCC, miR microarray and real-time PCR were performed using HK-2 and A-498 cells. Cell viability, invasion and wound healing assays were carried out for functional analysis after miR transfection. To determine target genes of miR, we used messenger RNA (mRNA) microarray and target scan algorithms to identify target oncogenes. A 3'UTR luciferase assay was also performed. Protein expression of target genes in ccRCC tissues was confirmed by immunohistochemistry and was compared with miR-584 expression in ccRCC tissues. RESULTS: Expression of miR-584 in RCC (A-498 and 769-P) cells was downregulated compared with HK-2 cells. Transfection of miR-584 dramatically decreased cell motility. The ROCK-1 mRNA was inhibited by miR-584 and predicted to be target gene. The miR-584 decreased 3'UTR luciferase activity of ROCK-1 and ROCK-1 protein expression. Low expression of miR-584 in ccRCC tissues was correlated with high expression of ROCK-1 protein. The knockdown of ROCK-1 by siRNA inhibited cell motility. CONCLUSION: miR-584 is a new tumour suppressor miR in ccRCC and inhibits cell motility through downregulation of ROCK-1.

The functional significance of microRNA-145 in prostate cancer.

BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in numerous cellular processes. Recent studies have shown aberrant expression of miRNAs in prostate cancer tissues and cell lines. On the basis of miRNA microarray data, we found that miR-145 is significantly downregulated in prostate cancer. METHODS AND RESULTS: We investigated the expression and functional significance of miR-145 in prostate cancer. The expression of miR-145 was low in all the prostate cell lines tested (PC3, LNCaP and DU145) compared with the normal cell line, PWR-1E, and in cancerous regions of human prostate tissue when compared with the matched adjacent normal. Overexpression of miR-145 in PC3-transfected cells resulted in increased apoptosis and an increase in cells in the G2/M phase, as detected by flow cytometry. Investigation of the mechanisms of inactivation of miR-145 through epigenetic pathways revealed significant DNA methylation of the miR-145 promoter region in prostate cancer cell lines. Microarray analyses of miR-145-overexpressing PC3 cells showed upregulation of the pro-apoptotic gene TNFSF10, which was confirmed by real-time PCR and western analysis. CONCLUSION: One of the genes significantly upregulated by miR-145 overexpression is the proapoptotic gene TNFSF10. Therefore, modulation of miR-145 may be an important therapeutic approach for the management of prostate cancer.

Synthesis of 6-aminomethyl derivatives of benzopyran-4-one with dual biological properties: anti-inflammatory-analgesic and antimicrobial.

A series of 6-aminomethyl-2-aryl-1-benzopyran-4-one derivatives (10-24) were synthesized. The compounds were tested for anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. Among the tested compounds, six compounds 11, 13, 16, 18, 21 and 23 showed higher degree of anti-inflammatory activity (>75% activity of standard drug ibuprofen). In addition to remarkable anti-inflammatory activity, analgesic activity was found to be comparable with that of the standard drug ibuprofen. Compounds 16 and 21 showed a significant GI protection (with respect to ulcerogenesis) and a marked decrease in lipid peroxidation values whereas compounds 11 and 16 were found to possess antimicrobial activity against Staphylococcus aureus, Escherichia coli, Rhizopus oryza and Penicillum citrum with an MIC of 10 microg/mL.

Protective effect of bezafibrate on streptozotocin-induced oxidative stress and toxicity in rats.

The present study was aimed to find out the protective effect of bezafibrate on lipid peroxidation (LPO), activities of both enzymatic and non-enzymatic antioxidants and histopathological examination of pancreas in streptozotocin (STZ)-induced diabetic rats. Experimental diabetes was induced by a single dose of STZ (60mg/kg, i.p.) injection. The oxidative stress was measured by tissue LPO level, reduced glutathione (GSH) content and by enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in liver and pancreas. Biochemical observations were further substantiated with histological examination of pancreas. The increase in blood glucose, LPO level with reduction in GSH content and decreased enzymatic activities were the salient features observed in diabetic control rats. Administration of bezafibrate (30mg/kg day, p.o.) for 15 days caused a significant reduction in blood glucose and LPO level in STZ treated rats (group III) when compared with diabetic control rats (group II). Furthermore, bezafibrate treated diabetic rats (group III) showed significant increase in the activities of both enzymatic and non-enzymatic antioxidants when compared to diabetic control rats (group II). Degenerative changes of pancreatic beta-cells in STZ treated rats were minimized to near normal morphology by administration of bezafibrate as evident by histopathological examination. The results obtained clearly indicate the role of oxidative stress in the induction of diabetes and suggest a protective effect of bezafibrate in this animal model.

Hepatoprotective effect of sesquiterpenes in turmeric.

Hepatoprotective effect of turmeric together with its sesquiterpenes and curcuminoids fractions were examined on D-galactosamine induced liver injury in rats. All the diets individually contained the turmeric extract, the curcuminoids fraction, and the sesquiterpenes fraction suppressed the increase of LDH, ALT, and AST levels caused by D-GalN treatment. Since few anti-oxidative activities are expected in the sesquiterpenes fraction, it is presumed that hepatoprotective mechanism of sesquiterpenes in turmeric is different from that of curuminoids.

Influence of corn processing and frequency of feeding on cow performance.

Twenty cows, including five fitted with rumen cannulae, were used to study the influence of corn processing and frequency of feeding on milk yield and ruminal fermentation characteristics. Cows were assigned to five treatments in a 5 x 5 Latin square experiment. Each period was 3 wk. Cows were fed 45% forage and 55% grain in a total mixed ration. Diets contained 35% corn either coarsely ground and fed once a day (1x), finely ground (FGC) fed 1x, steam-flaked (SFC) fed lx, FGC fed four times a day (4x), or SFC fed 4x. Processing of corn and frequency of feeding had no influence on dry matter intake. Digestibility of starch was increased 6 and 3 percentage units by feeding SFC corn compared with coarsely and finely ground corn, respectively. Cows fed SFC or FGC produced 4% more milk with lower fat content compared with coarsely ground corn. Increasing the feeding frequency did not improve milk fat content. The fat-corrected milk yield was not different among treatments. Feeding SFC resulted in a low acetate-to-propionate ratio in the rumen fluid than FGC. Cows fed SFC produced 45 and 115 g more milk protein per cow/d than cows fed FGC or coarse, respectively. With the value of increased milk protein observed in this study, it would be more economical to feed SFC or finely ground corn to dairy cows compared with coarse ground. The breakeven price of flaking corn in this study was $32 and $12/metric tonne compared with coarse and FGC, respectively. Based on a survey conducted by the authors, the price of flaking corn in the United States ranged between $7 to $22/metric tonne during year 2000.

Physical and motor development in male and female rat offspring prenatally exposed to gamma radiation.

The effects of radiation on physical and motor development of male and female rats exposed to ionizing radiation in utero were studied. Rats were exposed to three different doses of radiation (150 rad, 15 rad and 6.8 rad, considered as high, moderate and low doses of radiation respectively) on the 20th day of prenatal life. Exposure to 150 rad contributed to significantly lower body weights of both male and female rat offspring. Upper jaw tooth eruption was delayed in 150 rad treated male offspring, as well as in 15 rad and 150 rad treated female offspring. Cliff-avoidance response was delayed in 6.8 rad, 15 rad, and 150 rad treated male offspring; and 150 rad treated female offspring. Lower jaw tooth eruption, eye opening, and crawling were not affected by radiation in male or female animals. Results indicate that radiation affected the developmental parameters of both male and female rat offspring, and sex of the offspring played no role in the magnitude of radiation induced damages.

Locomotion and physical development in rats treated with ionizing radiation in utero.

Effects of ionizing radiation on the emergence of locomotor skill, and physical development were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Results indicated that relatively moderate (15 rad) to high (150 rad) doses of radiation had effects on certain locomotion and physical development parameters. Exposure to 150 rad delayed pivoting, cliff-avoidance, upper jaw tooth eruption, and decreased body weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption were marginally delayed in the 150 rad treated animals. Exposure to 15 rad delayed pivoting and cliff-avoidance.

Brain myelination in rats treated with ionizing radiation in utero.

Effects of ionizing radiation on brain myelination and some physical development parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with three different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Exposure to 150 rad reduced body, brain, ovary, kidney, heart and spleen weights. Prenatal exposure to 150 rad of radiation reduced the cerebral cortex weight by 22 percent at 30 days of age, and 20 percent at 52 days of age which caused a reduction in cerebral cortex myelin content by 20 and 23 percent at the ages of 30 and 52 days respectively. This dose did not affect the myelin content of the cerebellum or the brain stem, or the myelin concentration (mg myelin/g brain tissue) of the cerebral cortex, cerebellum, and the brain stem. The cerebral cortex weight of the 15 rad treated rats was reduced at the age of 30 days. Exposure to 15 rad, and 6.8 rad did not affect either the myelin content or the myelin concentration of these brain areas.