Publications by authors named "Mohammad Uddin"

279 Publications

CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case-control study combined with a meta-analysis.

Hum Cell 2021 May 5. Epub 2021 May 5.

Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Sonapur, 3814, Noakhali, Bangladesh.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by communication deficits, impaired social interactions, repetitive and stereotyped behaviors with restricted interests, and connected with the interaction between environmental factors and genetic vulnerability. CNTNAP2 gene has been extensively investigated for ASD and related neurodevelopment diseases. However, previous studies have resulted in an inconsistent outcome. Based on this fact, we conducted a case-control study followed by a meta-analysis to investigate the association of rs7794745 and rs2710102 polymorphisms with ASD. A total of 216 autistic children and 240 healthy volunteers were recruited, and genotyping was performed using the PCR-RFLP method. We observed that SNP rs7794745 revealed a significantly (p < 0.05) increased association with the development of ASD in children in all genetic models. No significant association was found for rs2710102 with ASD. Besides, rs2710102 exhibited a significant association with language impairment in TC genotype, C allele, and dominant model. From the meta-analysis of both SNPs, we found a significant association in codominant 1, 2, and the dominant model of rs2710102 and codominant 1 and dominant model of rs7794745 with ASD. Our case-control study suggests that rs7794745 polymorphism is associated with ASD, while rs2710102 is correlated with language impairment. Moreover, meta-analysis results indicated the association between both rs7794745 and rs2710102 polymorphisms and ASD.
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http://dx.doi.org/10.1007/s13577-021-00546-8DOI Listing
May 2021

Evaluating Energy Generation Capacity of PVDF Sensors: Effects of Sensor Geometry and Loading.

Materials (Basel) 2021 Apr 10;14(8). Epub 2021 Apr 10.

UniSA STEM, University of South Australia, Mawson Lakes, SA 5095, Australia.

This paper focuses on the energy generating capacity of polyvinylidene difluoride (PVDF) piezoelectric material through a number of prototype sensors with different geometric and loading characteristics. The effect of sensor configuration, surface area, dielectric thickness, aspect ratio, loading frequency and strain on electrical power output was investigated systematically. Results showed that parallel bimorph sensor was found to be the best energy harvester, with measured capacitance being reasonably acceptable. Power output increased with the increase of sensor's surface area, loading frequency, and mechanical strain, but decreased with the increase of the sensor thickness. For all scenarios, sensors under flicking loading exhibited higher power output than that under bending. A widely used energy harvesting circuit had been utilized successfully to convert the AC signal to DC, but at the sacrifice of some losses in power output. This study provided a useful insight and experimental validation into the optimization process for an energy harvester based on human movement for future development.
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http://dx.doi.org/10.3390/ma14081895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069537PMC
April 2021

Microneedles: A New Generation Vaccine Delivery System.

Micromachines (Basel) 2021 Apr 14;12(4). Epub 2021 Apr 14.

College of Medicine, QU Health, Qatar University, Doha P.O. Box 2731, Qatar.

Transdermal vaccination route using biodegradable microneedles is a rapidly progressing field of research and applications. The fear of painful needles is one of the primary reasons most people avoid getting vaccinated. Therefore, developing an alternative pain-free method of vaccination using microneedles has been a significant research area. Microneedles comprise arrays of micron-sized needles that offer a pain-free method of delivering actives across the skin. Apart from being pain-free, microneedles provide various advantages over conventional vaccination routes such as intramuscular and subcutaneous. Microneedle vaccines induce a robust immune response as the needles ranging from 50 to 900 μm in length can efficiently deliver the vaccine to the epidermis and the dermis region, which contains many Langerhans and dendritic cells. The microneedle array looks like band-aid patches and offers the advantages of avoiding cold-chain storage and self-administration flexibility. The slow release of vaccine antigens is an important advantage of using microneedles. The vaccine antigens in the microneedles can be in solution or suspension form, encapsulated in nano or microparticles, and nucleic acid-based. The use of microneedles to deliver particle-based vaccines is gaining importance because of the combined advantages of particulate vaccine and pain-free immunization. The future of microneedle-based vaccines looks promising however, addressing some limitations such as dosing inadequacy, stability and sterility will lead to successful use of microneedles for vaccine delivery. This review illustrates the recent research in the field of microneedle-based vaccination.
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http://dx.doi.org/10.3390/mi12040435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070939PMC
April 2021

Cartiotonic steroids affect monolayer permeability in lymphatic endothelial cells.

Mol Cell Biochem 2021 Apr 18. Epub 2021 Apr 18.

Orion Institute for Translational Medicine, Temple, TX, USA.

Edema is common in preeclampsia (preE), a hypertensive disorder of pregnancy. Cardiotonic steroids (CTSs) such as marinobufagenin (MBG) are involved in the pathogenesis of preE. To assess whether CTSs are involved in the leakage of lymphatic endothelial cell (LEC), we evaluated their effect on monolayer permeability of LECs (MPLEC) in culture. A rat mesenteric LECs were treated with DMSO (vehicle), and CTSs (MBG, CINO, OUB) at concentrations of 1, 10, and 100 nM. Some LECs were pretreated with 1 μM L-NAME (N-Nitro-L-Arginine Methyl Ester) before adding 100 nM MBG or cinobufotalin (CINO). Expression of β-catenin and vascular endothelial (VE)-cadherin in CTS-treated LECs was measured by immunofluorescence and MPLEC was quantified using a fluorescence plate reader. Western blot was performed to measure β-catenin and VE-cadherin protein levels and myosin light chain 20 (MLC20) phosphorylation. MBG (≥ 1 nM) and CINO (≥ 10 nM) caused an increase (p < 0.05) in the MPLEC compared to DMSO while ouabain (OUB) had no effect. Pretreatment of LECs with 1 μM L-NAME attenuated (p < 0.05) the MPLEC. The β-catenin expression in LECs was downregulated (p < 0.05) by MBG and CINO. However, there was no effect on the LECs tight junctions for the CINO group. VE-cadherin expression was downregulated (p < 0.05) by CINO, and MLC20 phosphorylation was upregulated (p < 0.05) by MBG. We demonstrated that MBG and CINO caused an increase in the MPLEC, which were attenuated by L-NAME pretreatment. The data suggest that CTSs exert their effect via nitric-oxide-dependent signaling pathway and may be involved in vascular leak syndrome of LEC lining in preE.
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http://dx.doi.org/10.1007/s11010-021-04147-9DOI Listing
April 2021

Prevalence and psychosocial impact of atopic dermatitis in Bangladeshi children and families.

PLoS One 2021 16;16(4):e0249824. Epub 2021 Apr 16.

Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.

Background: Skin conditions are the fourth leading cause of nonfatal disease globally, with atopic dermatitis (AD) a major and rising contributor. Though atopic dermatitis (AD) is rising in prevalence, little is known about its psychosocial effects on children and families in low- and middle-income countries (LMICs).

Methods: We conducted a community-based, cross-sectional survey of 2242 under-5 children in rural Bangladesh using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to measure AD prevalence and severity, the Patient-Oriented Eczema Measure (POEM) to measure severity, and the Infants' Dermatitis Quality of Life index (IDQoL) and Dermatitis Family Index (DFI) to measure quality of life.

Findings: Overall AD prevalence in under-five children was 11.9% [95% confidence interval (CI) 10.6-13.3%]. Prevalence was highest in children age 30-35 months [16.2% (95% CI 11.4-21.0)]. IDQoL was significantly higher in males (2.67) vs. females (1.95, p = 0.015), the lowest (3.06) vs. highest (1.63) wealth quintile (p<0.001), and among mothers with < primary (2.41) vs. > secondary (1.43) education (p = 0.039). POEM severity was correlated with IDQoL (r = 0.77, p<0.001) and DFI (r = 0.56, p<0.001). Severe disease as rated by caretakers was correlated with POEM (r = 0.73, p<0.001), IDQoL (r = 0.82, p<0.001) and DFI (r = 0.57, p<0.001).

Conclusions: Severe AD significantly affects quality of life for children and families in Bangladesh. As access to healthcare expands in LMICs, identification and treatment of both the medical and psychosocial morbidities associated with the disease are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249824PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051797PMC
April 2021

Investigating the mediating role of online learning motivation in the COVID-19 pandemic situation in Bangladesh.

J Comput Assist Learn 2021 Mar 2. Epub 2021 Mar 2.

Department of Business Administration, Faculty of Business & Social Science (FBSS) Bangladesh University of Professionals (BUP) Dhaka Bangladesh.

The purpose of this paper is to investigate the mediating role of online learning motivation (OLM) in the COVID-19 pandemic situation in Bangladesh by observing and comparing direct lectures (DL), instructor-learner interaction (ILI), learner-learner interaction (LLI), and internet self-efficacy (ISE) as predictors of OLM and online learning satisfaction (OLS). Data were collected from 442 undergraduate and graduate students from more than 35 universities in Bangladesh. To test the hypotheses, the PLS-SEM approach was applied using SmartPLS 3.0. The study shows a significant mediating role of OLM between the independent variables and learning satisfaction. In addition, DL, ILI, and ISE are shown to be significant predictors of student satisfaction. The findings have a number of valuable implications for education policy makers, universities, instructors, and students. Moreover, the study suggests some new research perspectives to overcome the limitations of this research and to gain precise knowledge on students' learning motivation and satisfaction regarding other online classes for different categories of students (e.g., high school and college, professional, and PhD).
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http://dx.doi.org/10.1111/jcal.12535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014261PMC
March 2021

Restoring the endothelial barrier function in the elderly.

Mech Ageing Dev 2021 Apr 2;196:111479. Epub 2021 Apr 2.

School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, USA.

Endothelial barrier dysfunction in the elderly has been associated with severe disorders, including acute respiratory distress syndrome, sepsis and COVID-19. Herein we deliver an opinion regarding the development of alternative therapeutic avenues to counteract the pathogenesis of the corresponding diseases.
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http://dx.doi.org/10.1016/j.mad.2021.111479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017911PMC
April 2021

The mA RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis.

Mol Cancer 2021 04 4;20(1):61. Epub 2021 Apr 4.

Division of Cancer Biology, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, 44109, USA.

The mA RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the mA modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the mA modification in the target mRNAs as well as noncoding RNA transcripts. mA modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the mA RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the mA modification and its regulators also render them as potential druggable targets for the treatment of cancer.
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http://dx.doi.org/10.1186/s12943-021-01356-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019509PMC
April 2021

Investigation of the Pharmacological Properties of Nees through Experimental Approaches.

Life (Basel) 2021 Feb 25;11(3). Epub 2021 Feb 25.

Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy.

Nees is used locally in Ayurvedic medicine to treat coughs and cardiovascular diseases. This study explored its pharmacological potential through in vivo and in vitro approaches for the metabolites extracted (methanolic) from the stems of . A qualitative phytochemical analysis revealed the presence of numerous secondary metabolites. The methanol extract of stems (MELHS) showed a strong antioxidative activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assays, and in the quantitative (phenolic and flavonoid) assay. Clot lysis and brine shrimp lethality bioassays were applied to investigate the thrombolytic and cytotoxic activities, respectively. MELHS exhibited an expressive percentage of clot lysis (33.98%) with a moderately toxic (115.11 μg/mL) effect. The in vivo anxiolytic activity was studied by an elevated plus maze test, whereas the antidepressant activity was examined by a tail suspension test and forced swimming test. During the anxiolytic evaluation, MELHS exhibited a significant dose-dependent reduction of anxiety, in which the 400 mg/kg dose of the extract showed 78.77 ± 4.42% time spent in the open arm in the elevated plus maze test. In addition, MELHS demonstrated dose-dependent and significant activities in the tail suspension test and forced swimming test, whereas the 400 mg/kg dose of the extract showed 87.67 ± 6.40% and 83.33 ± 6.39% inhibition of immobile time, respectively. Therefore, the current study suggests that could be a potential source of anti-oxidative, cytotoxic, thrombolytic, anxiolytic, and antidepressant agents. Further study is needed to determine the mechanism behind the bioactivities.
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http://dx.doi.org/10.3390/life11030180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996513PMC
February 2021

Mechanical, structural and biodegradation characteristics of fibrillated silk fibres and papers.

Int J Biol Macromol 2021 May 2;179:20-32. Epub 2021 Mar 2.

Institute for Frontier Materials, Deakin University, Waurn Ponds, Victoria 3216, Australia. Electronic address:

We characterised fibres and papers of microfibrillated silk from Bombyx mori produced by mechanical and enzymatic process. Milling increased the specific surface area of fibres from 1.5 to 8.5 m/g and that enzymatic pre-treatment increased it further to 16.5 m/g. These fibrils produced a uniform, significantly strong (tenacity 55 Nm/g) and stiff (Young's modulus > 2 GPa) papers. Enzymatic pre-treatment did not reduce molecular weight and tensile strength of papers but significantly improved fibrillation. Silk remained highly crystalline throughout the fibrillation process. Protease biodegradation was more rapid after fibrillation. Biodegradation was impacted by structural change due to enzymatic pre-treatment during the fibrillation. Biodegraded silk had much higher thermal degradation temperature. The unique combination of high strength, slow yet predicable degradation and controllable wicking properties make the materials ideally suited to biomedical and healthcare applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.211DOI Listing
May 2021

Study of nitrate levels in fruits and vegetables to assess the potential health risks in Bangladesh.

Sci Rep 2021 Feb 25;11(1):4704. Epub 2021 Feb 25.

Department of Food Engineering and Tea Technology, Shahjalal University of Science and Technology, Sylhet , 3114, Bangladesh.

Nitrate is a chemical compound naturally present in fruits and vegetables. This study aims at assessing the nitrate levels and health risks arising from high consumption of fruits and vegetables in Bangladesh. Sixteen species of fruits and vegetables were examined for nitrates using High-Performance Liquid Chromatography with Photo Diode Array (PDA) detector. Ward's hierarchical cluster analysis was carried out to identify the cluster of tested fruits and vegetables for the nitrate contents. A point estimate of the daily intake was applied to find the health risks that arise due to elevated levels of nitrate in fruits and vegetables. The results show that root and tuber vegetables accumulate significantly higher levels of nitrate in comparison to fruits and fruit vegetables (P < 0.05). In cluster analysis, the nitrate accumulation of fruits and vegetables show four clear clusters contributing to 29.54%, 7.17%, 4.42%, and 58.57% of the total nitrate content in the entire sample. The risk assessment of the Estimated Daily Intake (EDI) and Health Risk Index (HRI) of almost all the tested samples was in the acceptable range, except for radish, thereby indicating the acceptance of risk due to nitrate intake in Bangladesh. As nitrate may have had risk factor for health, during cultivation and storing the product should be properly monitored.
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http://dx.doi.org/10.1038/s41598-021-84032-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907138PMC
February 2021

Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study.

Front Immunol 2020 2;11:616450. Epub 2021 Feb 2.

Laboratoire des Pathogènes Emergents, Fondation Mérieux, Centre International de Recherche en Infectiologie, INSERM U1111, Lyon, France.

Background: Tuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon- (IFN-) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN- levels according to sputum culture conversion and immune cell counts during treatment.

Methods: This multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated HBHA (produced in rmsHBHA). Plasma IFN- levels were then assessed by ELISA.

Findings: Between December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN- increased significantly throughout treatment (0.086 IU/ml at T0 . 1.03 IU/ml at T2, p < 0.001) while QFT-P IFN- remained constant (TB1: 0.53 IU/ml at T0 . 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (<14%) or high neutrophil percentages (>79%) at baseline had significantly lower IFN- responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN- responses) and low rmsHBHA IFN- at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70-80%) but not their specificity (<30%).

Conclusion: We showed that QFT-P and rmsHBHA IFN- responses were associated with rates of sputum culture conversion. Our results support a growing body of evidence suggesting that rmsHBHA IFN- discriminates between the different stages of TB, from active disease to controlled infection. However, further work is needed to confirm the specificity of QFT-P and rmsHBHA IGRAs for treatment monitoring.
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http://dx.doi.org/10.3389/fimmu.2020.616450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885528PMC
February 2021

Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.

Cancer Med 2021 03 14;10(5):1829-1838. Epub 2021 Feb 14.

Department of Pharmacy, Noakhali Science and Technology University, Noakhali, Bangladesh.

Objective: Cervical cancer is a gynecological health problem, affecting nearly 500,000 women each year worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical carcinoma risk. We have carried out this case-control study to investigate the association of INSIG2 rs6726538 (A; T), HLA-DRB1 rs9272143 (T; C), and GCNT1P5 rs7780883 (G; A) with cervical cancer.

Methods: The present study recruited 234 cervical cancer patients as cases and 212 healthy females as controls. We have applied the tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method for genotyping.

Results: The SNP rs6726538 was significantly associated with increased risk of cervical cancer in all genetic models (AT vs. AA: OR = 3.30, 95% CI = 2.19-4.97, p < 0.0001; TT vs. AA: OR = 8.72, 95% CI = 3.87-19.7, p < 0.0001; AT+TT vs. AA: OR = 3.87, 95% CI = 2.61-5.73, p < 0.0001; T vs. A: OR = 2.97, 95% CI = 2.20-4.01, p < 0.0001) except the recessive model which showed a significantly reduced risk (TT vs. AA+AT: OR = 0.20, 95% CI = 0.09-0.44, p = 0.0001). rs9272143 showed significantly reduced risk for the additive model 1, dominant model, and allelic model (TC vs. TT: OR = 0.46, 95% CI = 0.31-0.70, p = 0.0004; TC+CC vs. TT: OR = 0.47 95% CI = 0.32-0.70, p = 0.0002; C vs. T: OR = 0.56, 95% CI = 0.40-0.78, p = 0.0006, respectively). The third variant, rs7780883, was significantly associated with increased risk in additive model 2, dominant, and allelic models (AA vs. GG: OR = 5.08, 95% CI = 2.45-10.5, p < 0.0001; GA+AA vs. GG: OR = 1.54, 95% CI = 1.06-2.24, p = 0.0237; A vs. G: OR = 1.88, 95% CI = 1.34-2.52, p < 0.0001, consecutively), whereas recessive model reduced the risk of cervical cancer (AA vs. GG+GA: OR = 0.20, 95% CI = 0.09-0.41, p < 0.0001). Other models of these SNPs were not associated with cervical cancer. All significant associations for three SNPs withstand after Bonferroni correction except the additive model 2 of rs7780883.

Conclusion: Our study concludes that INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 polymorphisms may contribute to the development of cervical cancer in the Bangladeshi population.
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http://dx.doi.org/10.1002/cam4.3782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940232PMC
March 2021

An Efficient Watermarking Approach Based on LL and HH Edges of DWT-SVD.

SN Comput Sci 2021 8;2(2):82. Epub 2021 Feb 8.

Department of Computer Science and Engineering, Jahangirnagar University, Savar, Dhaka, 1342 Bangladesh.

Digital watermarking is playing a vital role in the improvement of authentication, security, and copyright protection in today's digital transformation. The performance of this technique is shown to be impressive around the globe. Text, audio, video, and image data are acted as watermarks in the digital platform. In this article, a hybrid watermarking scheme is proposed to furnish the robustness and protection of digital data. This hybrid scheme is a form of discrete wavelet transform (DWT) and singular value decomposition (SVD). The embedding and extracting features are carried out through multi-level operations of DWT and SVD. Various attacks are added to the proposed method to justify the robustness of the watermark. In the end, the suggested approach is contrasted with existing methods to confirm the supremacy.
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http://dx.doi.org/10.1007/s42979-021-00478-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869427PMC
February 2021

Meta-Analysis of Prospective Studies of Risk stratification by Syntax Score for Unprotected Left Main Coronary Artery Revascularization.

Am J Cardiol 2021 05 10;146:138-139. Epub 2021 Feb 10.

Department of Internal Medicine, University of Connecticut, Hartford, Connecticut.

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http://dx.doi.org/10.1016/j.amjcard.2021.02.003DOI Listing
May 2021

Hsp90 inhibition protects the brain microvascular endothelium against oxidative stress.

Brain Disord 2021 Mar 11;1. Epub 2021 Jan 11.

School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.

The brain endothelium is an integral element of the blood-brain barrier (BBB). Dysfunction of this formation due to increased generation of reactive oxygen species (ROS) progresses the establishment of neurological disorders including stroke and traumatic brain injury. Heat shock protein 90 inhibitors are anti-inflammatory agents, and their activities are mediated, at least in part, by P53. This is a tumor suppressor protein which regulates the opposing activities of Rac1 and RhoA in the cellular cytoskeleton. In the present study we investigated the role of Hsp90 inhibitors in the HO-induced brain endothelium breakdown, by employing human cerebral microvascular endothelial cells (hCMEC/D3). Our findings suggest that HO downregulates P53 by enhancing the P53 suppressor mouse double minute 2 homolog (MDM2), as well as by increasing the apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref1). The HO - triggered violation of the brain endothelium barrier was reflected in measurements of transendothelial resistance, and the increased expression of the key cytoskeletal modulators cofilin and myosin light chain 2 (MLC2). Treatment of the hCMEC/D3 cells with Hsp90 inhibitors counteracted those events, and reduced the generation of the hydrogen peroxide - induced reactive oxygen species. Hence, our study suggests that Hsp90 inhibition supports the BBB integrity, and may represent a promising therapeutic approach for disorders associated with brain endothelium breakdown; including COVID-19.
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http://dx.doi.org/10.1016/j.dscb.2020.100001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869856PMC
March 2021

Green synthesis, characterization, application and functionality of nitrogen-doped MgO/graphene nanocomposite.

Environ Sci Pollut Res Int 2021 Feb 1. Epub 2021 Feb 1.

Mining and Metallurgical Engineering Department, Faculty of Engineering, Assiut University, Assiut, 71516, Egypt.

A facile, feasible, and green synthesis via an electrochemical exfoliation process was applied to synthesize nitrogen-doped MgO/graphene nanocomposite (N-MgO/G). The N-MgO/G nanocomposite was characterized by several analytical techniques including X-ray photoelectron spectroscopy, X-ray powder diffraction, transmission electron microscopy, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, selected area electron diffraction, and elemental mapping analysis. N-MgO/G nanocomposite was then applied to adsorb lead metal ions (Pb) from aqueous solutions. The N-MgO/G nanocomposite demonstrated a remarkably high Langmuir maximum adsorption capacity (294.12 mg/g) for Pb ions under the optimum experimental conditions at a pH of 5.13, time of 35 min, dose of 0.025 g, the concentration of 400 mg/L, and a temperature of 36 °C. Adsorption kinetics results fitted with a pseudo-second-order model and a thermodynamic study showed that Pb adsorption is an endothermic process. The practical application of N-MgO/G was also investigated to test its applicability in real water samples collected from different sources such as deionized water, tap water, wastewater, and river water.
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http://dx.doi.org/10.1007/s11356-021-12628-zDOI Listing
February 2021

Virtual screening and molecular dynamics simulation study of plant-derived compounds to identify potential inhibitors of main protease from SARS-CoV-2.

Brief Bioinform 2021 03;22(2):1402-1414

Department of Genetic Engineering and Biotechnology, University of Rajshahi, Administration Building 1, Rajshahi 6205, Bangladesh.

The new coronavirus (SARS-CoV-2) halts the world economy and caused unbearable medical emergency due to high transmission rate and also no effective vaccine and drugs has been developed which brought the world pandemic situations. The main protease (Mpro) of SARS-CoV-2 may act as an effective target for drug development due to the conservation level. Herein, we have employed a rigorous literature review pipeline to enlist 3063 compounds from more than 200 plants from the Asian region. Therefore, the virtual screening procedure helps us to shortlist the total compounds into 19 based on their better binding energy. Moreover, the Prime MM-GBSA procedure screened the compound dataset further where curcumin, gartanin and robinetin had a score of (-59.439, -52.421 and - 47.544) kcal/mol, respectively. The top three ligands based on binding energy and MM-GBSA scores have most of the binding in the catalytic groove Cys145, His41, Met165, required for the target protein inhibition. The molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, solvent accessible surface area, radius of gyration and hydrogen bond analysis from simulation trajectories. The post-molecular dynamics analysis also confirms the interactions of the curcumin, gartanin and robinetin in the similar binding pockets. Our computational drug designing approach may contribute to the development of drugs against SARS-CoV-2.
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http://dx.doi.org/10.1093/bib/bbaa428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929365PMC
March 2021

Strain-specific clearance of seed-dependent tau aggregation by lithium-induced autophagy.

Biochem Biophys Res Commun 2021 Mar 28;543:65-71. Epub 2021 Jan 28.

Department of Diagnosis, Prevention and Treatment of Dementia, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Department of Neurology, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Different conformational strains of tau have been implicated in the clinicopathological heterogeneity of tauopathies. In this study, we hypothesized that distinct strains are degraded in a different manner. Lithium, a drug for bipolar disorder, had previously been reported to reduce aggregation-prone protein content by promoting autophagy. Here, we assessed the effects of lithium on tau aggregates using different tauopathy brain seeds. SH-SY5Y cells were transfected with C-terminal tau fragment Tau-CTF24 (residues 243-441), and Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) brain seeds were introduced. After 48-h lithium treatment, sarkosyl-insoluble fractions were prepared. Lithium treatment was found to reduce the amount of insoluble tau and p62, and increase LC3-II levels along with the number of autophagic vacuoles in AD-seeded cells. The effects were lower in case of CBD seeds, and comparable between PSP and AD seeds. An inhibitor of myo-inositol monophosphatase (IMPase) also demonstrated similar effects. Overall, the study suggested that aggregated tau protein is degraded by lithium-induced autophagy, influencing IMPase in a strain-specific manner.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.113DOI Listing
March 2021

The mechanistic role of thymoquinone in Parkinson's disease: focus on neuroprotection in pre-clinical studies.

Curr Mol Pharmacol 2021 Jan 5. Epub 2021 Jan 5.

Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052. Australia.

Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, apoptosis, thereby protects neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies have been remained to be investigated to clarify its neuroprotective role.
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http://dx.doi.org/10.2174/1874467214666210105140944DOI Listing
January 2021

The Possible Relationship between the Abuse of Tobacco, Opioid, or Alcohol with COVID-19.

Healthcare (Basel) 2020 Dec 22;9(1). Epub 2020 Dec 22.

College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.

Substance use disorder has been frequently reported to increase the risk of infectious diseases, which might be owing to the sharing of contaminated inhalation, smoking, vaping, or injection equipment. This review analyzes the recent literature with the aim to put in light the possible relationship between the abuse of different substances (Tobacco, opioid, and Alcohol) with coronavirus disease (COVID-19). Multiple studies confirmed that cigarette smoking affects the respiratory system by increasing the expression of angiotensin-converting enzyme-2 (ACE2) receptors, which have a significant association with COVID-19 infection rate and disease severity. Studies conducted regarding the association of opioid use disorder (OUD) and COVID-19 infection severity are limited; however, opioids can lead to both respiratory depression and kidney injuries, causing poor prognosis for those with COVID-19 infections. People with alcohol use disorders are at risk of developing acute lung injury and severe COVID-19 infection. Alcohol consumption during the COVID-19 pandemic has two possible scenarios: either increased or decreased based on situations. SUD has been frequently reported to have a positive relationship with COVID-19 severity Further studies are needed to understand the effects of opioids and alcohol abuse on COVID-19.
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http://dx.doi.org/10.3390/healthcare9010002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822153PMC
December 2020

Cadmium accumulation, subcellular distribution and chemical fractionation in hydroponically grown Sesuvium portulacastrum [Aizoaceae].

PLoS One 2020 28;15(12):e0244085. Epub 2020 Dec 28.

Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Xiamen, China.

Sesuvium portulacastrum is a well-known halophyte with considerable Cd accumulation and tolerance under high Cd stress. This species is also considered as a good candidate of Cd phytoremediation in the polluted soils. However, the mechanism of Cd accumulation, distribution and fractionation in different body parts still remain unknown. Seedlings of Sesuvium portulacastrum were studied hydroponically under exposure to a range of Cd concentrations (50 μM or μmol/L to 600 μM or μmol/L) for 28 days to investigate the potential accumulation capability and tolerance mechanisms of this species. Cd accumulation in roots showed that the bio-concentration factor was > 10, suggesting a strong ability to absorb and accumulate Cd. Cd fractionation in the aboveground parts showed the following order of distribution: soluble fraction > cell wall > organelle > cell membrane. In roots, soluble fraction was mostly predominant than other fractions. Cd speciation in leaves and stems was mainly contained of sodium chloride and deionised water extracted forms, suggesting a strong binding ability with pectin and protein as well as with organic acids. In the roots, inorganic form of Cd was dominant than other forms of Cd. It could be suggested that sodium chloride, deionised water and inorganic contained form of Cd are mainly responsible for the adaption of this plant in the Cd stress environment and alleviating Cd toxicity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244085PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769616PMC
March 2021

Metformin in acute respiratory distress syndrome: An opinion.

Exp Gerontol 2021 03 10;145:111197. Epub 2020 Dec 10.

School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. Electronic address:

Senior individuals are more susceptible to the irreversible outcomes of endothelial barrier dysfunction, the hallmark of Acute Respiratory Distress Syndrome (ARDS). The Severe Acute Respiratory Syndrome Coronovirus 2 (SARS-CoV-2) - inflicted ARDS delivers the devastating outcomes of the COVID-19 worldwide. Endothelial hyperpermeability has been associated with both the progression and establishment of the COVID-19 - related respiratory failure. In the present study we investigated the in vitro effects of Metformin in the permeability of bovine pulmonary artery endothelial cells. Our preliminary results suggest that moderate doses (0.1, 0.5, 1.0 mM) of this anti-diabetic agent enhance the vascular barrier integrity, since it produces an increase in the transendothelial resistance of endothelial monolayers. Thus, we speculate that Metformin may deliver a new therapeutic possibility in ARDS, alone or in combination with other barrier enhancers.
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http://dx.doi.org/10.1016/j.exger.2020.111197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834182PMC
March 2021

Meningococcal Vaccines: Challenges and Prospects.

Vaccines (Basel) 2020 Dec 4;8(4). Epub 2020 Dec 4.

Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.

is a gram-negative bacterium that causes a severe acute infection, called the meningococcal disease [...].
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http://dx.doi.org/10.3390/vaccines8040738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761900PMC
December 2020

Hospitalization of Pediatric Enteric Fever Cases, Dhaka, Bangladesh, 2017-2019: Incidence and Risk Factors.

Clin Infect Dis 2020 12;71(Suppl 3):S196-S204

Child Health Research Foundation, Dhaka, Bangladesh.

Background: Enteric fever causes substantial morbidity and mortality in low- and middle-income countries. Here, we analyzed Surveillance for Enteric Fever in Asia Project (SEAP) data to estimate the burden of enteric fever hospitalization among children aged <15 years and identify risk factors for hospitalization in Bangladesh.

Methods: SEAP used hospital surveillance paired with a community-based health-care utilization assessment. In SEAP hospital surveillance, blood was obtained for culture from children aged <15 years with ≥3 days of fever. In the hospital catchment area, a health-care utilization survey (HCUS) was conducted to estimate the proportion of febrile children hospitalized at the study hospitals. We analyzed hospital surveillance and HCUS data to estimate the health care-adjusted incidence of enteric fever hospitalization, and conducted univariable and multivariable logistic regressions.

Results: From July 2017 through June 2019, 2243 laboratory-confirmed enteric fever cases were detected in 2 study hospitals; 673 (30%) were hospitalized. The health care-adjusted incidence of enteric fever hospitalization among children <15 years old was 303/100 000 children/year (95% confidence interval [CI], 293-313). Salmonella Typhi contributed most to the enteric fever hospitalization incidence (277/100 000 children/year; 95% CI, 267-287). The incidence was highest among children aged 2 to <5 years (552/100 000 children/year; 95% CI, 522-583), followed by those aged <2 years (316/100 000 children/year; 95% CI, 288-344). Factors independently associated with enteric fever hospitalization included fever duration, diarrhea, vomiting, abdominal pain, and leukocytopenia.

Conclusions: We estimated a high burden of hospitalization due to enteric fever among children aged <5 years in Bangladesh. The introduction of a typhoid conjugate vaccine would protect children from typhoid and avert typhoid hospitalizations.
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http://dx.doi.org/10.1093/cid/ciaa1356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705877PMC
December 2020

Synergistic effect of deep ball burnishing and HA coating on surface integrity, corrosion and immune response of biodegradable AZ31B Mg alloys.

Mater Sci Eng C Mater Biol Appl 2021 Jan 27;118:111459. Epub 2020 Aug 27.

University of South Australia, UniSA STEM, Mawson Lakes, SA 5095, Australia.

The fast degradation and consequent loss of mechanical integrity is a major problem of biodegradable Mg alloy, which limits its clinical viability. This paper presents the influence of a synergistic approach combining deep ball burnishing and hydroxyapatite (HA) coating on biomechanical integrity, degradation and immune response of Mg alloy (AZ31B). The burnishing resulted in smooth surface topography, increased hardness from 0.87 to 1.45 GPa and induced microstructural disturbances with deformation twins/twin bands, which enabled formation of a dense and compact platelet-like crystals HA coating of 110 μm thickness. Compared to the untreated and burnished specimens, the burnished + HA coated surface provided remarkably higher corrosion resistance as indicated by lower corrosion current density and smaller mass loss. HA coating and surface integrity enhancement by burnishing were predominantly responsible for improved corrosion resistance. HA coating on the burnished surface exhibited hydrophilic properties and adequate bonding strength. While the modified surfaces promoted cell growth, the burnished + HA surface outperformed in exhibiting less pro-inflammatory and high anti-inflammatory cytokines, demonstrating that the treated surfaces were not posing any threat to immune cells. The findings indicate that the synergistic surface treatment can be a viable means to enhance corrosion resistance and immune response of Mg alloys implants.
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http://dx.doi.org/10.1016/j.msec.2020.111459DOI Listing
January 2021

Application of the Farm Simulation Model approach on economic loss estimation due to Coronavirus (COVID-19) in Bangladesh dairy farms-strategies, options, and way forward.

Trop Anim Health Prod 2020 Nov 23;53(1):33. Epub 2020 Nov 23.

International Farm Comparison Network (IFCN) Dairy Research Center, University of Kiel, Schauenburger Str. 116, 24118, Kiel, Germany.

The objective of this paper is to quantify the economic loss of the dairy farms due to the pandemic novel Coronavirus (COVID-19) infection by analyzing the real-time data of two typical farms (BD-2 and BD-14 cow) in Bangladesh and propose a strategic plan of action to make policy decisions in order to support the dairy industry. The International Farm Comparison Network (IFCN) Farm Simulation Approach and Technology Impact Policy Impact Calculations (TIPICAL) model was used considering with Corona (WC) and without Corona (WOC). The Integrated Dairy Research Network (IDRN) database (January 2019 to July 2020) was used for simulation of IFCN two typical farms. The milk price is decreased by 17% and feed price is increased by 3.7% due to COVID-19 in March which was used as the base for farm simulation. This resulted in a decrease in milk yield by 7.9% and 8.9% for small household and family farms, respectively. The cost of milk production increased by 19.10% and 10.9% for household and family farms, respectively. This has an overall negative impact on farm income which accounted for national economic loss from dairy farms in Bangladesh to 4.43 million USD/day (36.84 crore BDT). This loss has been fluctuated from April onward and was higher in June (3.83 million USD/day) due to a combination of COVID-19, flood, and seasonality effect on lowering milk production. At the same time, the farmers' response to the resilience capacity (liquidity, operating profit margin, and financial performance) to combat COVID-19-induced situation has been declined substantially. Based on this, we conclude that the government might take a strategy to support farmers by providing financial support for increasing the operating capital and decreasing the cost of milk production. The outcome of this study is expected to be beneficial for policymakers, farmers, and processors in Bangladesh and similar other countries elsewhere.
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http://dx.doi.org/10.1007/s11250-020-02471-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682769PMC
November 2020

Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via β-catenin-activated RNA methylation.

FASEB Bioadv 2020 Nov 2;2(11):653-667. Epub 2020 Sep 2.

School of Basic Pharmaceutical and Toxicological Sciences College of Pharmacy University of Louisiana at Monroe Monroe Louisiana USA.

Glucosylceramide synthase (GCS) is a key enzyme catalyzing ceramide glycosylation to generate glucosylceramide (GlcCer), which in turn serves as the precursor for cells to produce glycosphingolipids (GSLs). In cell membranes, GSLs serve as essential components of GSL-enriched microdomains (GEMs) and mediate membrane functions and cell behaviors. Previous studies showed that ceramide glycosylation correlates with upregulated expression of p53 hotspot mutant R273H and cancer drug resistance. Yet, the underlying mechanisms remain elusive. We report herewith that globotriaosylceramide (Gb3) is associated with cSrc kinase in GEMs and plays a crucial role in modulating expression of p53 R273H mutant and drug resistance. Colon cancer cell lines, either WiDr homozygous for missense-mutated (R273H) or SW48/TP53-Dox bearing heterozygous mutant (R273H), display drug resistance with increased ceramide glycosylation. Inhibition of GCS with Genz-161 (GENZ 667161) resensitized cells to apoptosis in these p53 mutant-carrying cancer cells. Genz-161 effectively inhibited GCS activity, and substantially suppressed the elevated Gb3 levels seen in GEMs of p53-mutant cells exposed to doxorubicin. Complex formation between Gb3 and cSrc in GEMs to activate β-catenin was detected in both cultured cells and xenograft tumors. Suppression of ceramide glycosylation significantly decreased Gb3-cSrc in GEMs, β-catenin, and methyltransferase-like 3 for mA RNA methylation, thus altering pre-mRNA splicing, resulting in upregulated expression of wild-type p53 protein, but not mutants, in cells carrying p53 R273H. Altogether, increased Gb3-cSrc complex in GEMs of membranes in response to anticancer drug induced cell stress promotes expression of p53 mutant proteins and accordant cancer drug resistance.
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http://dx.doi.org/10.1096/fba.2020-00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655095PMC
November 2020