Publications by authors named "Abul Kalam Azad"

82 Publications

Blood biochemical parameters for assessment of COVID-19 in diabetic and non-diabetic subjects: a cross-sectional study.

Int J Environ Health Res 2021 Jan 27:1-14. Epub 2021 Jan 27.

Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology , Sylhet, Bangladesh.

This study aims to identify blood biomarkers for rapidly predicting progression and severity assessment of COVID-19 in type 2 diabetic (DM) and non-DM (NDM) patients. Among 211 hospitalized patients suspected of COVID-19, 98 were confirmed COVID-19 by rRT-PCR. The COVID-19 positive group contained 58 DM and 40 NDM patients with total death 9 of which 7 were males and 6 were DM, indicating males and DM individuals as more susceptible to COVID-19. Blood biomarkers notably serum ferritin, CRP, D-dimer, ALT, troponin I, and Hb1Ac were significantly (p < 0.05) higher in COVID-19 patients. Ferritin and HbA1c levels were significantly (p < 0.05) higher in DM than NDM COVID-19 patients. The present study suggests that ferritin and HbA1c levels for DM patients, and ferritin, D-dimer, ALT for NDM patients could be routinely used as biomarkers for progression and severity assessment of COVID-19. CRP and Troponin-I could be the predictor only for poor prognosis of COVID-19.
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http://dx.doi.org/10.1080/09603123.2021.1879741DOI Listing
January 2021

mosaic and partial monosomy of chromosome 21 in a case with superior vena cava duplication.

Mol Cytogenet 2020 12;13:45. Epub 2020 Sep 12.

Department of Pathology/Molecular Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1635 Poplar St., Bronx, NY 10461 USA.

Background: Full or partial monosomy of chromosome (chr) 21 is a very rare abnormal cytogenetic finding. It is characterized by variable sizes and deletion breakpoints on the long arm (q) of chr 21 that lead to a broad spectrum of phenotypes that include an increased risk of birth defects, developmental delay and intellectual deficit.

Case Presentation: We report a 37-year-old G1P0 woman initially screened by non-invasive prenatal testing with no positive findings that was followed by an 18-week anatomy scan with a fetal finding of duplication of the superior vena cava (SVC). The medical and family history was otherwise uneventful. After appropriate genetic counseling, amniocentesis was performed to evaluate suspected chromosomal anomalies.

Conclusions: Interphase fluorescent in situ hybridization revealed loss of one chr 21 signal that was further delineated by chromosomal microarray analysis on uncultured amniocytes as a terminal 10 Mb deletion on chr 21q. Karyotype and microarrays on cultured amniocytes showed two cell lines for a mosaic 21q terminal deletion and monosomy 21. The combined molecular cytogenetics results reported following the ISCN 2016 guideline as mos 46,XX,del(21)(q22)dn[20]/45,XX,-21dn[10].nuc ish(D21S342/D21S341/D21S259x1)[100].arr[GRCh37] 21q11.2q22.12(15412676_36272993)x1~2,21q22.12q22.3(36431283_47612400)x1. Parental chromosomal analysis revealed normal karyotypes. Thus, this was a mosaic full and partial monosomy of chr 21 in a case with SVC duplication. Despite the association of congenital heart disease with monsomy 21 we could not find any published literature or online databases for this cytogenetic abnormality. The patient terminated the pregnancy following the abnormal molecular cytogenetic results due to the possible challenges the baby would face if carried to term.
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http://dx.doi.org/10.1186/s13039-020-00513-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488852PMC
September 2020

Antibacterial activity of graphene oxide nanosheet against multidrug resistant superbugs isolated from infected patients.

R Soc Open Sci 2020 Jul 15;7(7):200640. Epub 2020 Jul 15.

Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.

Graphene oxide (GO) is a derivative of graphene nanosheet which is the most promising material of the decade in biomedical research. In particular, it has been known as an antimicrobial nanomaterial with good biocompatibility. In this study, we have synthesized and characterize GO and checked its antimicrobial property against different Gram-negative and Gram-positive multidrug drug resistant (MDR) hospital superbugs grown in solid agar-based nutrient plates with and without human serum through the utilization of agar well diffusion method, live/dead fluorescent staining and genotoxicity analysis. No significant changes in antibacterial activity were found in these two different conditions. We also compare the bactericidal capability of GO with some commonly administered antibiotics and in all cases the degree of inhibition is found to be higher. The data presented here are novel and show that GO is an effective bactericidal agent against different superbugs and can be used as a future antibacterial agent.
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http://dx.doi.org/10.1098/rsos.200640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428267PMC
July 2020

Kinetics, detergent compatibility and feather-degrading capability of alkaline protease from AKAL7 and AKAL11 produced with fermentation of organic municipal solid wastes.

J Environ Sci Health A Tox Hazard Subst Environ Eng 2020 15;55(11):1339-1348. Epub 2020 Jul 15.

Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet, Bangladesh.

Alkaline proteases having activity and stability at alkaline pH possess a large variety of applications in many industries. Growing renewed interest urges the need to find a single alkaline protease with promising properties to be used in different industrial processes. Herein, alkaline proteases produced through fermentation of cheap and easily available organic municipal solid wastes by AKAL7 and AKAL11 were purified to investigate their kinetic and thermodynamic parameters, detergent compatibility, dehairing and feather-degrading capability. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the purified protease from and had molecular mass of ∼45 and 75 kDa, respectively. The protease from and showed highest activity at 55 and 50 °C having low 1.17 and 0.567 mg/mL and high 416.67 and 333.33 µmole/min, respectively. The activation energy and temperature quotient of protease from and were 26.52 and 65.75 kJ/mole, and 1.0004 and 1.0003 at 20-55 and 20-50 °C, respectively. Thermodynamics analysis revealed the formation of more ordered enzyme-substrate complexes along with spontenity of enzyme reaction. The protease from exhibited better compatibility at higher concentration of detergents compared to that from However, both proteases could retain more than 80% of the activity in the presence of 0.1% commercial laundry detergents. The purified protease from the both sources could degrade almost 90% of barbs and 40% of dry weight of the native feather and that from could dehair cow skin. Results reported herein suggest that the alkaline protease from AKAL7 and AKAL11 has biotechnological implications in detergent, leather and poultry feather processing industries.
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http://dx.doi.org/10.1080/10934529.2020.1794207DOI Listing
October 2020

Exploring mental health needs and services among affected population in a cyclone affected area in costal Bangladesh: a qualitative case study.

Int J Ment Health Syst 2020 5;14:12. Epub 2020 Mar 5.

2Institute of Disaster Management & Vulnerability Studies, University of Dhaka, Dhaka, Bangladesh.

Background: Bangladesh, one of the most densely populated countries in the world has been ranked 9th on the Climate Risk Index for 2017: the 10 most affected countries & 7th on the Long-Term Climate Risk Index: the 10 countries most affected from 1998 to 2017. Every year it is afflicted with various climatic disasters including floods, hurricanes and cyclones. Apart from the obvious devastation of lives and property, there is a huge increase in clinical diseases when these disasters occur. Mental health of affected persons after these disasters is a topic that is often neglected by local and national level.

Methods: A qualitative case study was conducted on perceived need on mental health support & availability of such services in a cyclone affected area in rural Bangladesh. Ten (10) key informant interviews (KIIs) with different stakeholders and ten (10) in-depth interviews (IDIs) with affected people were taken.

Findings: We found that cyclones had numerous psychosocial impacts on the population including acute stress disorder, sleep disorder, post-traumatic stress disorders (PTSDs), generalized anxiety disorders, suicidal ideation and depression. The survivors had specific needs for receiving support. Children, elderly and women were perceived to be more vulnerable. The government and NGOs had no specific action plans and initiatives to address these issues and support the mental health of affected population. There was a visible gap in finding effective ways to provide affected people with the required mental health & psycho-social services (MHPSS).

Conclusion: Resilient, responsive and self-sustaining health systems for this vulnerable population are required. Implementation of effective mental health programs and strong mental health policies remain a challenge in Bangladesh where there is a cultural fatalistic acceptance of mental health issues.
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http://dx.doi.org/10.1186/s13033-020-00351-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059662PMC
March 2020

Encapsulation of Black Seed Oil in Alginate Beads as a pH-Sensitive Carrier for Intestine-Targeted Drug Delivery: In Vitro, In Vivo and Ex Vivo Study.

Pharmaceutics 2020 Mar 2;12(3). Epub 2020 Mar 2.

Advanced Drug Delivery Laboratory, Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Malaysia.

Black seed oil (BSO) has been used for various therapeutic purposes around the world since ancient eras. It is one of the most prominent oils used in nutraceutical formulations and daily consumption for its significant therapeutic value is common phenomena. The main aim of this study was to develop alginate-BSO beads as a controlled release system designed to control drug release in the gastrointestinal tract (GIT). Electrospray technology facilitates formulation of small and uniform beads with higher diffusion and swelling rates resulting in process performance improvement. The effect of different formulation and process variables was evaluated on the internal and external bead morphology, size, shape, encapsulation efficiency, swelling rate, in vitro drug release, release mechanism, ex vivo mucoadhesive strength and gastrointestinal tract qualitative and quantitative distribution. All the formulated beads showed small sizes of 0.58 ± 0.01 mm (F8) and spherical shape of 0.03 ± 0.00 mm. The coefficient of weight variation (%) ranged from 1.37 (F8) to 3.93 (F5) ng. All formulations (F1-F9) were studied in vitro for release characteristics and swelling behaviour, then the release data were fitted to various equations to determine the exponent (ns), swelling kinetic constant (ks), swelling rate (%/h), correlation coefficient (r) and release kinetic mechanism. The oil encapsulation efficiency was almost complete at 90.13% ± 0.93% in dried beads. The maximum bead swelling rate showed 982.23 (F8, r = 0.996) in pH 6.8 and the drug release exceeded 90% in simulated gastrointestinal fluid (pH 6.8). Moreover, the beads were well distributed throughout various parts of the intestine. This designed formulation could possibly be advantageous in terms of increased bioavailability and targeted drug delivery to the intestine region and thus may find applications in some diseases like irritable bowel syndrome.
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http://dx.doi.org/10.3390/pharmaceutics12030219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150899PMC
March 2020

Enhanced Carrier Screening for Spinal Muscular Atrophy: Detection of Silent (SMN1: 2 + 0) Carriers Utilizing a Novel TaqMan Genotyping Method.

Lab Med 2020 Jul;51(4):408-415

Department of Pathology, Montefiore Medical Center at Albert Einstein College of Medicine, Bronx, New York.

Background: Individuals whose copies of the survival motor neuron 1 (SMN1) gene exist on the same chromosome are considered silent carriers for spinal muscular atrophy (SMA). Conventional screening for SMA only determines SMN1 copy number without any information regarding how those copies are arranged. A single nucleotide variant (SNV) rs143838139 is highly linked with the silent carrier genotype, so testing for this SNV can more accurately assess risk to a patient of having an affected child.

Methods: Using a custom-designed SNV-specific Taqman genotyping assay, we determined and validated a model for silent-carrier detection in the laboratory.

Results: An initial cohort of 21 pilot specimens demonstrated results that were 100% concordant with a reference laboratory method; this cohort was utilized to define the reportable range. An additional 177 specimens were utilized for a broader evaluation of clinical validity and reproducibility. Allelic-discrimination analysis demonstrated tight clustering of genotype groupings and excellent reproducibility, with a coefficient of variation for all genotypes ranging from 1% to 4%.

Conclusion: The custom-developed Taqman SNV genotyping assay we tested provides a rapid, accurate, and cost-effective method for routine SMA silent-carrier screening and considerably improves detection rates of residual risk for SMA carriers.
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http://dx.doi.org/10.1093/labmed/lmz088DOI Listing
July 2020

Identification of Efflux Pump Genes and Detection of Mutation in Efflux Repressor from Omeprazole Responsive Multidrug-Resistant Isolates Causing Urinary Tract Infections.

Microbiol Insights 2019 4;12:1178636119889629. Epub 2019 Dec 4.

Department of Genetic Engineering & Biotechnology, Shahjalal University of Science and Technology, Sylhet-3114, Bangladesh.

Antimicrobial resistance poses a threat in the treatment of infectious diseases in Bangladesh as well as in the world. Multidrug-resistant (MDR) Enterobacteriaceae, the most common cause of one such infectious disease, urinary tract infection (UTI), has contributed to the escalating problem of selecting empiric antibiotics against UTIs. The aim of this study was to investigate the presence of the efflux pump in MDR isolates from UTI in the North-East region of Bangladesh, to isolate and characterize the AcrAB-TolC efflux pump genes of these locally isolated strains and to do mutation analysis of the efflux pump repressor gene to understand the AcrAB-TolC efflux pump mechanism. In the presence of omeprazole, an efflux pump inhibitor, every MDR isolate showed increased susceptibility to at least 1 of the 7 antibiotics investigated, indicating that efflux pump might be involved in their antibiotic resistance. Omeprazole decreased the minimum inhibitory concentration of every antibiotics being investigated by 2- to 8-fold. DNA and the deduced amino acid sequences of the polymerase chain reaction (PCR) products analyzed by bioinformatics tools revealed that the chromosomal and genes were present in all MDR and antibiotic-susceptible isolates. However, the deduced amino acid sequences of the amplification refractory mutation system (ARMS) PCR product of the gene revealed that the substitution of arginine to cysteine at position 45 of AcrR was observed only in the MDR whose antibiotic susceptibility increased in the presence of omeprazole. Data reported herein support the notion that the increased antibiotic susceptibility of the MDR isolates in the presence of omeprazole might be due to efflux pump(s) inhibition and the AcrAB-TolC efflux pump might be a contributor to antibiotic resistance when the mutation of arginine to cysteine occurs at position 45 of AcrR.
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http://dx.doi.org/10.1177/1178636119889629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893934PMC
December 2019

Fgd5 is a Rac1-specific Rho GEF that is selectively inhibited by aurintricarboxylic acid.

Small GTPases 2021 Mar 10;12(2):147-160. Epub 2019 Oct 10.

Department of Cell Biology, University of Alberta , Edmonton, Alberta, Canada.

Rho proteins are signalling molecules that control cellular dynamics, movement and morphological changes. They are activated by Rho guanine-nucleotide exchange factors (Rho GEFs) that transduce upstream signals into Rho-mediated activation of downstream processes. Fgd5 is a Rho GEF involved in angiogenesis and its target Rho protein for this process has been linked to Cdc42 activation. Here, we examined the function of purified Fgd5, specifically, which Rho proteins it activates and pinpoint the structural domains required for enzymatic activity. Using a GEF enzyme assay, we found that purified Fgd5 showed preferential activation of Rac1 and direct binding of Rac1 in pull-down and co-immunoprecipitation assays. Structural comparisons showed that the Fgd5 DH domain is highly similar to the Rac1 GEF, TrioN, supporting a role for Fgd5 as a Rac1 GEF. Compounds that bind to purified Fgd5 DH-PH protein were identified by screening a small molecule library via surface plasmon resonance. The effects of eleven ligands were further examined for their ability to inhibit the Fgd5 GEF enzymatic activity and Rac1 interaction. From these studies, we found that the compound aurintricarboxylic acid, and to a lesser extent mitoxantrone dihydrochloride, inhibited both Fgd5 GEF activation of Rac1 and their interaction. Aurintricarboxylic acid had no effect on the activity or binding of the Rac1 GEF, TrioN, thus demonstrating the feasibility of selectively disrupting Rho GEF activators. : a.a.: amino acid; ATA: aurintricarboxylic acid; DH: Dbl homology; DOCK: dictator of cytokinesis; Fgd: faciogenital dysplasia; GEF: guanine-nucleotide exchange factor; GST: glutathione -transferase; LOPAC: library of pharmacologically active compounds; PH: pleckstrin homology; PDB: protein data bank; s.e.m.: standard error of the mean; SPR: surface plasmon resonance.
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http://dx.doi.org/10.1080/21541248.2019.1674765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849785PMC
March 2021

Fabrication of poly(D, L-lactic acid) nanoparticles as delivery system for sustained release of L-theanine.

IET Nanobiotechnol 2019 Sep;13(7):742-747

Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore - 632014, TN, India.

L-theanine is present in tea as a unique, free, non-protein amino acid. Due to various beneficial effects on brain activity, it is widely used as a nutraceutical. After consumption, it is rapidly absorbed and metabolised followed by excretion through urine. Therefore, the authors developed an L-theanine delivery system by encapsulating into polymeric nanoparticles to release it slowly and make it available for a longer period of time. Poly(D, L-lactic acid) nanoparticle (PLANP) was fabricated by the double emulsion method and L-theanine was encapsulated into it (PLANP-T). Spherical nanoparticles with a hydrodynamic diameter of 247 and 278 nm and surface charge of -14.5 and -25.7 mV for PLANP and PLANP-T, respectively, were fabricated. The Fourier transform infrared spectroscopic data indicated encapsulation of L-theanine into PLANP. The PLANP showed high L-theanine encapsulation capacity (71.65%) with a sustained release character. The maximum release (66.3%) of L-theanine was recorded in pH 7.3 at 48 h. The release kinetics followed the Higuchi model and the release mechanism was determined as super case-II transport (erosion). This slow release will make it available to the target tissue for a longer period of time (sustain release effect) and will also avoid immediate metabolism and clearance from the circulation.
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http://dx.doi.org/10.1049/iet-nbt.2018.5248DOI Listing
September 2019

Improving coverage of civil registration and vital statistics, Bangladesh.

Bull World Health Organ 2019 Sep 23;97(9):637-641. Epub 2019 Jul 23.

Coordination and Reforms, Cabinet Division, Dhaka, Bangladesh.

Problem: Bangladesh has no national system for registering deaths and determining their causes. As a result, policy-makers lack reliable and complete data to inform public health decisions.

Approach: In 2016, the government of Bangladesh introduced a pilot project to strengthen the civil registration and vital statistics system and generate cause of death data in Kaliganj Upazila. Community-based health workers were trained to notify births and deaths to the civil registrar, and to conduct verbal autopsy interviews with family members of a deceased person. International experts in cause-of-death certification and coding trained master trainers on how to complete the international medical certificate of cause of death. These trainers then trained physicians and coders.

Local Setting: Kaliganj Upazila has an estimated population of 304 600, and 5600 births and 1550 deaths annually. Health assistants and family welfare assistants make regular visits to households to track certain health outcomes.

Relevant Changes: Following the start of the project in 2016, the number of births registered within 45 days rose from 873 to 4630 in 2018. The number of deaths registered within 45 days increased from 458 to 1404. During this period, health assistants conducted 7837 verbal autopsy interviews. Between January 2017 and December 2018, 105 master trainers and more than 7000 physicians were trained to complete the international medical certificate of cause of death and they completed more than 12 000 certificates.

Lessons Learnt: Training community-based health workers, physicians and coders were successful approaches to improve death registration completeness and availability of cause-of-death data.
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http://dx.doi.org/10.2471/BLT.18.219162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705501PMC
September 2019

Bangladesh's digital health journey: reflections on a decade of quiet revolution.

WHO South East Asia J Public Health 2019 09;8(2):71-76

Directorate General of Health Services, Ministry of Health and Family Welfare, Dhaka, Bangladesh

Bangladesh has made remarkable progress in digital health in recent years. Through one of the world’s largest deployments to date of the open-source District Health Information Software 2 (DHIS2), the country now has a national public sector health data warehouse. Information from previously fragmented data systems is now unified in a common data repository, enabling data exchange for health information systems and decision-making. Work is ongoing to create lifetime electronic health records for all citizens that can be transferred between health facilities. Extensive customization of open-source software has laid the foundations for a national digital networking system. Initiatives have focused on producing digital solutions to aid priorities such as strengthening the health system as a whole as well as supporting specific technical interventions, for example improving the civil registration and vital statistics system. Digital solutions have also supported the Bangladesh health workforce strategy through a set of registries that electronically captures and maintains human resource information for the entire public health sector, including monitoring staff attendance through the use of low-cost biometric fingerprint time-attendance machines. Citizens are encouraged to engage in shaping health services via a web-based complaints and suggestions system, and a new system to raise health awareness via public digital displays has started in Dhaka. Strong support at the highest political level has been critical to the success of efforts to introduce these innovations. The endeavour has also generated a cadre of enthusiastic eHealth proponents, who are focused on further strengthening and expanding the existing systems and on harnessing the vast amount of information amassed at the central data repository through big data analysis, artificial intelligence and machine learning.
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http://dx.doi.org/10.4103/2224-3151.264849DOI Listing
September 2019

Biodegradation of reactive textile dye Novacron Super Black G by free cells of newly isolated AZ26 and spp obtained from textile effluents.

Heliyon 2019 Jul 11;5(7):e02068. Epub 2019 Jul 11.

Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.

Bacteria were isolated from effluents of textile industries and screened by their capability to decolorize at least one of eight reactive dyes used in the textile industries. Three isolates having the capability to decolorize the highest number of dyes with more than 25% of decolorization were identified as AZ26, AZ27 and sp. AZ28 based on morphological, cultural, biochemical characteristics, and 16S rDNA sequence analysis. The decolorization capability of these three bacterial isolates was optimized under different physicochemical conditions by using Novacron Super Black G (NSB-G), one of the eight reactive dyes commonly used in textile industries. These bacterial isolates grew well in the presence of up to 500 mg L of NSB-G and showed decolorization of approximately 90% at 200 mg L of NSB-G after 96 h of cultivation at 37 °C and pH 8.0 under static condition. Decolorization of NSB-G by the bacterial isolates was investigated using UV-VIS spectrophotometry and Fourier Transform Infrared Spectroscopy (FTIR) analysis. The UV-visible absorbance spectra and the FTIR spectrum of the decolorized NSB-G significantly differed from those of the parent dye, indicating that the NSB-G was degraded by the bacterial isolates. High decolorization extent supports the notion that the bacterial isolates reported herein might have potential in the biological treatment of dyeing mill effluents.
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http://dx.doi.org/10.1016/j.heliyon.2019.e02068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626096PMC
July 2019

Scheelite type SrBaWO (x = 0.1, 0.2, 0.3) for possible application in Solid Oxide Fuel Cell electrolytes.

Sci Rep 2019 Jun 24;9(1):9173. Epub 2019 Jun 24.

Faculty of Integrated Technologies, Universiti Brunei Darussalam, Jalan Tungku Link, Bandar Seri Begawan, BE 1410, Brunei Darussalam.

Polycrystalline scheelite type SrBaWO (x = 0.1, 0.2 & 0.3) materials were synthesized by the solid state sintering method and studied with respect to phase stability and ionic conductivity under condition of technological relevance for SOFC applications. All compounds crystallized in the single phase of tetragonal scheelite structure with the space group of I4/a. Room temperature X-ray diffraction and subsequent Rietveld analysis confirms its symmetry, space group and structural parameters. SEM illustrates the highly dense compounds. Significant mass change was observed to prove the proton uptake at higher temperature by TG-DSC. All compound shows lower conductivity compared to the traditional BCZY perovskite structured materials. SBW with x = 0.3 exhibit the highest ionic conductivity among all compounds under wet argon condition which is 1.9 × 10 S cm at 1000 °C. Since this scheelite type compounds show significant conductivity, the new series of SBW could serve in IT-SOFC as proton conducting electrolyte.
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http://dx.doi.org/10.1038/s41598-019-45668-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591329PMC
June 2019

Partial purification and characterization of serine protease produced through fermentation of organic municipal solid wastes by A3 and A2.

J Genet Eng Biotechnol 2018 Jun 18;16(1):29-37. Epub 2017 Oct 18.

Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.

Proteolytic bacteria isolated from municipal solid wastes (MSW) were identified as A3 and A2 based on 16S rDNA sequencing. Protease produced through fermentation of organic MSW by these bacteria under some optimized physicochemical parameters was partially purified and characterized. The estimated molecular mass of the partially purified protease from and was approximately 25 and 38 kDa, respectively. Protease from both sources showed low K 0.3 and 0.5 mg ml and high V 333 and 500 µmole min at 40 °C, and thermodynamics analysis suggested formation of ordered enzyme-substrate (E-S) complexes. The activation energy (E) and temperature quotient (Q) of protease from and were 16.2 and 19.9 kJ/mol, and 1.4 and 1.3 at temperature range from 20 to 40 °C, respectively. Protease of the both bacterial isolates was serine and cysteine type. The protease retained approximately 97% of activity in the presence of sodium dodecyl sulphate. It was observed that the purified protease of could remove blood stains from white cotton cloth and degrade chicken flesh remarkably. Our study revealed that organic MSW can be used as raw materials for bacterial protease production and the protease produced by A3 might be potential for applications.
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http://dx.doi.org/10.1016/j.jgeb.2017.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296650PMC
June 2018

Dyslipidaemia as a risk factor for erectile dysfunction in type 2 diabetes mellitus patients.

Diabetes Metab Syndr 2019 Jan - Feb;13(1):748-753. Epub 2018 Nov 30.

Schools of Public Health and Preventive Medicine, Monash University, Australia. Electronic address:

Background: Despite epidemiological studies worldwide have documented erectile dysfunction (ED) as a major complication of type 2 diabetes Mellitus (T2DM) in men, only limited research reported on determinants of ED in this population. The study aimed at examining the association of ED with dyslipidaemia in T2DM patients.

Methods: The study enrolled 813 consecutive eligible adult male T2DM patients attending the endocrinology departments of a tertiary teaching hospital in Bangladesh. Sexual function was assessed using modified International Index of Erectile Function (IIEF) in face-to-face interview and collected along with sociodemographic information. Diabetes and lipid profile and treatment history were collected from patient's treatment records. Association of ED with dyslipidaemia was assessed using multivariable logistic regression adjusting for potential confounders.

Result: Prevalence of ED among the T2DM patients was very high (72.7%), of which around half had moderated-to-severe ED. Odds of having dyslipidaemia among T2DM patients with ED is 2.3 times higher than those without. The odds increased by approximately 3 fold for an abnormal High Density Lipoprotein level and by 2.7 fold for abnormal Low Density Lipoprotein.

Conclusion: Dyslipidaemia was associated with increased ED risk among T2DM. Abnormal lipoprotein level particularly were found to pose greater risk.
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http://dx.doi.org/10.1016/j.dsx.2018.11.052DOI Listing
April 2019

Relationship among obesity, blood lipids and insulin resistance in Bangladeshi adults.

Diabetes Metab Syndr 2019 Jan - Feb;13(1):444-449. Epub 2018 Oct 11.

Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh. Electronic address:

Introduction: Insulin resistance (IR) and abnormal lipid profiles are the risk factors for cardiovascular diseases in obesity. To clarify the relationship of the changes in insulin resistance, body weight and lipid profile, the present study was performed on Bangladeshi adults, total of 1500 individuals at the time of their general health examination in the hospital.

Methods: After exclusion of other endocrine diseases, the remaining 772 patients were classified as IR ≥ 2 and IR < 2 based on the homeostatic model assessment-estimated insulin resistance (HOMA-IR) index. The endocrine disease free subjects were further clustered based on age, gender and obesity. The anthropometric and biochemical profiles were statistically analyzed and correlated with IR ≥ 2 and IR<2 groups as well as other clusters of the subjects. Apart from some disparities, notable differences were observed in all anthropometric data.

Results: Total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and serum insulin levels were significantly higher in IR ≥ 2 group in comparison with IR<2 group. Obesity and dyslipidemia were associated as prevalent components of IR. Generalized linear model revealed that TC: LDL and TG: HDL had significant effect on IR. Age group II (41-60 years old) subjects had significantly higher lipid profile compared to age group I (20-40 years old) and age group III (61-80 years old).

Conclusions: Results reported herein support the notion that lipoprotein ratios might be the reliable biomarkers to evaluate IR.
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http://dx.doi.org/10.1016/j.dsx.2018.10.015DOI Listing
May 2019

Study on the Perception of Staff and Students of a University on Community Pharmacy Practice in Ipoh, Perak, Malaysia.

J Pharm Bioallied Sci 2018 Oct-Dec;10(4):226-231

Faculty of Pharmacy, International Islamic University Malaysia (IIUM), 25200 Kuantan, Pahang, Malaysia.

Background: In Malaysia, community pharmacies play an important and vital role in both urban and rural areas with approximately 30% of 12,000 registered pharmacists with annual retention certificate practicing in community pharmacies. The main objective of this study was to find the perception of respondents on the value and necessity of pharmacists.

Materials And Methods: The questionnaire was divided into two sections: the first section assessed the visits to community pharmacies, purpose, interaction with pharmacy staffs, professional fee, and improvements to pharmacy practices; the second section evaluated the characteristics of respondents including an e-consent form. Data were analyzed using the Statistical Package for the Social Sciences software (version 11.5).

Results: The highest number of respondents (66.1%) consulted with the pharmacists for cough and cold, 33.1% for gastric and stomach ailments, and 28.9% for diarrhea and constipation. Only 34% of cases were handled by the pharmacists, whereas 52.1% by the sales assistant. Approximately 88.5% showed satisfaction with the counseling provided. A total of 46.3% did not know whom they dealt with, whereas 51.2% wanted personal attention of the pharmacists instead of the sales assistants. However, 66.9% of respondents preferred to a private consultation room. Records of only 32.2% of respondents were secured by the pharmacies, whereas 42.1% showed interest to pay a professional fee. Moreover, 83.3% agreed the fee of RM5 only, whereas 20.8% agreed to RM10. Among the respondents, majority agreed to pay a fee willingly, but approximately 30% stayed neutral.

Conclusion: There is a need for the community pharmacists to play vital roles firsthand at the front desk to serve the patients professionally instead of handing over the responsibilities to the sales assistant.
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http://dx.doi.org/10.4103/JPBS.JPBS_80_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266647PMC
December 2018

In vitro evaluation of Roxb. for thrombolytic, antioxidant, membrane stabilizing and antimicrobial activities.

Nat Prod Res 2020 Aug 26;34(16):2394-2397. Epub 2018 Nov 26.

Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia.

The key purpose of this experiment was to evaluate the thrombolytic, antioxidant, membrane stabilizing and antimicrobial potentials of crude ethanol extracts (CEE) of whole plant, organic and aqueous soluble fractions (OF & AQSF). CEE showed the highest (44.63%) clot lysis activity compared to streptokinase (64.35%). In DPPH study, petroleum ether soluble fraction (PSF) has exhibited IC50 of 18.83 μg/mL while the standard ascorbic acid was 2.48 µg/mL. AQSF profoundly inhibited the lysis of erythrocytes (66.20%) which was insignificantly different (p > 0.05) to acetylsalicylic acid (71.98%), the reference. However, AQSF showed a significantly stronger level of protection against heat-induced hemolysis (64.80%) as compared with the acetylsalicylic acid (78.90%). CEE, OF and AQSF have displayed reasonable growth of inhibition of tested bacteria compared to negative control and standard drug (77.50 mg of GAE/g).
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http://dx.doi.org/10.1080/14786419.2018.1538216DOI Listing
August 2020

A simple method for extracting both active oily and water soluble extract (WSE) from (L.) seeds using a single solvent system.

Nat Prod Res 2019 Aug 24;33(15):2266-2270. Epub 2018 Jul 24.

f Microbiology , University of Science and Technology Chittagong , Chittagong , Bangladesh.

The current study provides a way of extraction for both active NSO and WSE from seeds using 98% methanol. About 1 kg of ground seeds was macerated by 1:2.5 w/v (g/mL) for 72 hours. After rotary evaporation and 7 days of continuous drying and chilling at 50 and 4 °C, NSO and WSE were obtained at the same instant. Solubility tests of 24 solvents and 11 thin layer chromatographic analyses while 2, 2-diphenyl-1-picrylhydrazyl free radical scavenging assay of NSO (73.66) , WSE (33.32) and NSO + WSE (78.22) against ascorbic acid (IC50 = 4.28 mg/mL) was performed. WSE was found to be highly soluble in water and 5% NaOH exhibiting the same R value of 0.95 for EtOH:DMSO (9:1) against the honey. WSE has revealed more than twofold higher anti-oxidant activity than others. Formulation of WSE with honey may provide better targeted hydrophilic drug delivery systems.
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http://dx.doi.org/10.1080/14786419.2018.1493587DOI Listing
August 2019

Production and partial characterization of dehairing alkaline protease from AKAL7 and AKAL11 by using organic municipal solid wastes.

Heliyon 2018 Jun 7;4(6):e00646. Epub 2018 Jun 7.

Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.

Alkaline proteases have applications in numerous industries. In this study, we have isolated and screened proteolytic bacteria from poultry wastes mixed soil and identified two bacterial isolates as AKAL7 and AKAL11 based on 16S rDNA sequencing. Maximum level of protease production was achieved after 24 h of fermentation in a basal medium. The optimal temperature, initial pH of the media and agitation for alkaline protease production by these two isolates were 30 °C, pH 9.0 and 120 rpm, respectively. The both bacterial isolates produced maximum level of protease with 3.0% organic municipal solid wastes (OMSW) as the sole source of carbon and nitrogen under previously optimized fermentation conditions. In comparison with the shake flask, protease production increased about 2.5-fold in the bioreactor with reduction in fermentation period. The partial purification of protease resulted in a final 45.67 and 34.86-fold purified protease with a specific activity of 8335.34 and 9918.91 U/mg protein and a typical yield of 9.75 and 9.41% from and , respectively. The optimum temperature and pH of the partially purified protease from the both sources was 40 °C and pH 9.0, respectively. Protease from the both isolates was stable at pH 7.0-12.0 and at temperatures up to 50 °C. The effects of protease inhibitors indicated that the protease from might be serine and cysteine type and from might be cysteine type. Mg, K and Ca stimulated but Zn, Hg, Co and Fe strongly inhibited the protease activity. The partially purified protease from substantially dehaired cow skin and decomposed gelatinous compound from X-ray film. Our study revealed that OMSW can be used as raw material for production of bacterial extracellular protease and alkaline protease from might be potential for industrial and biotechnological applications.
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http://dx.doi.org/10.1016/j.heliyon.2018.e00646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042311PMC
June 2018

Emergency deployment of oral cholera vaccine for the Rohingya in Bangladesh.

Lancet 2018 05 10;391(10133):1877-1879. Epub 2018 May 10.

icddr,b (International Centre for Diarrhoeal Disease Research), Dhaka-1212, Bangladesh.

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http://dx.doi.org/10.1016/S0140-6736(18)30993-0DOI Listing
May 2018

Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration-resistant prostate cancer models.

Int J Cancer 2018 05 30;142(10):2163-2174. Epub 2018 Jan 30.

Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX.

Previous studies have shown that increased levels of chemokine receptor CXCR7 are associated with the increased invasiveness of prostate cancer cells. We now show that CXCR7 expression is upregulated in VCaP and C4-2B cells after enzalutamide (ENZ) treatment. ENZ treatment induced apoptosis (sub-G1) in VCaP and C4-2B cells, and this effect was further increased after combination treatment with ENZ and CCX771, a specific CXCR7 inhibitor. The levels of p-EGFR (Y1068), p-AKT (T308) and VEGFR2 were reduced after ENZ and CCX771 combination treatment compared to single agent treatment. In addition, significantly greater reductions in migration were shown after combination treatment compared to those of single agents or vehicle controls, and importantly, similar reductions in the levels of secreted VEGF were also demonstrated. Orthotopic VCaP xenograft growth and subcutaneous MDA133-4 patient-derived xenograft (PDX) tumor growth was reduced by single agent treatment, but significantly greater suppression was observed in the combination treatment group. Although overall microvessel densities in the tumor tissues were not different among the different treatment groups, a significant reduction in large blood vessels (>100 μm ) was observed in tumors following combination treatment. Apoptotic indices in tumor tissues were significantly increased following combination treatment compared with vehicle control-treated tumor tissues. Our results demonstrate that significant tumor suppression mediated by ENZ and CXCR7 combination treatment may be due, in part, to reductions in proangiogenic signaling and in the formation of large blood vessels in prostate cancer tumors.
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http://dx.doi.org/10.1002/ijc.31237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867246PMC
May 2018

Targeting the MYCN-PARP-DNA Damage Response Pathway in Neuroendocrine Prostate Cancer.

Clin Cancer Res 2018 02 14;24(3):696-707. Epub 2017 Nov 14.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC). Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro. ChIP-PCR assay revealed that N-MYC transcriptionally activates PARP1, PARP2, BRCA1, RMI2, and TOPBP1 through binding to the promoters of these genes. MYCN or PARP1 gene knockdown significantly reduced the expression of MYCN-PARP-DDR pathway genes and NED markers, and inhibition with MYCNsi and/or PARPsi, BRCA1si, or RMI2si significantly suppressed malignant activities, including cell viability, colony formation, and cell migration, in C4-2b4 and NCI-H660 cells. Targeting this pathway with AURKA inhibitor PHA739358 and PARP inhibitor olaparib generated therapeutic effects similar to those of gene knockdown and significantly suppressed tumor growth in both C4-2b4 and MDACC PDX144-13C subcutaneous models Our results identify a novel MYCN-PARP-DDR pathway that is driven by N-MYC in a subset of CRPC-Adeno and in NEPC. Targeting this pathway using and CRPC-Adeno and CRPC-Neuro models demonstrated a novel therapeutic strategy for NEPC. Further investigation of N-MYC-regulated DDR gene targets and the biological and clinical significance of MYCN-PARP-DDR signaling will more fully elucidate the importance of the MYCN-PARP-DDR signaling pathway in the development and maintenance of NEPC. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823274PMC
February 2018

Prediction of arsenic and antimony transporter major intrinsic proteins from the genomes of crop plants.

Int J Biol Macromol 2018 Feb 26;107(Pt B):2630-2642. Epub 2017 Oct 26.

Department of Life Science and Biotechnology, Shimane University, Shimane 690-8504, Japan.

Major intrinsic proteins (MIPs), commonly known as aquaporins, transport water and non-polar small solutes. Comparing the 3D models and the primary selectivity-related motifs (two Asn-Pro-Ala (NPA) regions, the aromatic/arginine (ar/R) selectivity filter, and Froger's positions (FPs)) of all plant MIPs that have been experimentally proven to transport arsenic (As) and antimony (Sb), some substrate-specific signature sequences (SSSS) or specificity determining sites (SDPs) have been predicted. These SSSS or SDPs were determined in 543 MIPs found in the genomes of 12 crop plants; the As and Sb transporters were predicted to be distributed in noduline-26 like intrinsic proteins (NIPs), and every plant had one or several As and Sb transporter NIPs. Phylogenetic grouping of the NIP subfamily based on the ar/R selectivity filter and FPs were linked to As and Sb transport. We further determined the group-wise substrate selectivity profiles of the NIPs in the 12 crop plants. In addition to two NPA regions, the ar/R filter, and FPs, certain amino acids especially in the pore line, loop D, and termini contribute to the functional distinctiveness of the NIP groups. Expression analysis of transcripts in different organs indicated that most of the As and Sb transporter NIPs were expressed in roots.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.10.153DOI Listing
February 2018

Effect of small proportion of butanol additive on the performance, emission, and combustion of Australian native first- and second-generation biodiesel in a diesel engine.

Environ Sci Pollut Res Int 2017 Oct 12;24(28):22402-22413. Epub 2017 Aug 12.

Department of Mechanical Engineering, Faculty of Engineering, Prince of Songkhla University, Chang Wat Songkhla, 90110, Thailand.

This paper aims to investigate the effect of the addition of 5% alcohol (butanol) with biodiesel-diesel blends on the performance, emissions, and combustion of a naturally aspirated four stroke multi-cylinder diesel engine at different engine speeds (1200 to 2400 rpm) under full load conditions. Three types of local Australian biodiesel, namely macadamia biodiesel (MB), rice bran biodiesel (RB), and waste cooking oil biodiesel (WCB), were used for this study, and the data was compared with results for conventional diesel fuel (B0). Performance results showed that the addition of butanol with diesel-biodiesel blends slightly lowers the engine efficiency. The emission study revealed that the addition of butanol additive with diesel-biodiesel blends lowers the exhaust gas temperature (EGT), carbon monoxide (CO), nitrogen oxide (NOx), and particulate matter (PM) emissions whereas it increases hydrocarbon (HC) emissions compared to B0. The combustion results indicated that in-cylinder pressure (CP) for additive added fuel is higher (0.45-1.49%), while heat release rate (HRR) was lower (2.60-9.10%) than for B0. Also, additive added fuel lowers the ignition delay (ID) by 23-30% than for B0. Finally, it can be recommended that the addition of 5% butanol with Australian biodiesel-diesel blends can significantly lower the NOx and PM emissions.
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http://dx.doi.org/10.1007/s11356-017-9920-6DOI Listing
October 2017

Temperature extraction in Brillouin optical time-domain analysis sensors using principal component analysis based pattern recognition.

Opt Express 2017 Jul;25(14):16534-16549

We propose and experimentally demonstrate the use of principal component analysis (PCA) based pattern recognition to extract temperature distribution from the measured Brillouin gain spectra (BGSs) along the fiber under test (FUT) obtained by Brillouin optical time domain analysis (BOTDA) system. The proposed scheme employs a reference database consisting of relevant ideal BGSs with known temperature attributes. PCA is then applied to the BGSs in the reference database as well as to the measured BGSs so as to reduce their size by extracting their most significant features. Now, for each feature vector of the measured BGS, we determine its best match in the reference database comprised of numerous reduced-size feature vectors of the ideal BGSs. The known temperature attribute corresponding to the best-matched BGS in the reference database is then taken as the extracted temperature of the measured BGS. We analyzed the performance of PCA-based pattern recognition algorithm in detail and compared it with that of curve fitting method. The experimental results validate that the proposed technique can provide better accuracy, faster processing speed and larger noise tolerance for the measured BGSs. Therefore, the proposed PCA-based pattern recognition algorithm can be considered as an attractive method for extracting temperature distributions along the fiber in BOTDA sensors.
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http://dx.doi.org/10.1364/OE.25.016534DOI Listing
July 2017

In silico identification and characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses.

Asian Pac J Trop Med 2017 Jun 1;10(6):529-538. Epub 2017 Jul 1.

Department of Genetic Engineering & Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh. Electronic address:

Objective: To explore a common B- and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV).

Methods: Membrane proteins F, G and M of HeV and NiV were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico.

Results: One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope (VDPLRVQWRNNSVIS) showed at least 66% identity with all NiV and HeV G protein sequences, while the 15-mer M-epitope (GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all NiV and HeV M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II (MHC II) and class-I (MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response.

Conclusions: Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against HeV and NiV. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.
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http://dx.doi.org/10.1016/j.apjtm.2017.06.016DOI Listing
June 2017

Optimization of some fermentation conditions for the production of extracellular amylases by using and isolates from organic kitchen wastes.

J Genet Eng Biotechnol 2017 Jun 21;15(1):59-68. Epub 2017 Mar 21.

Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet-3114, Bangladesh.

Amylolytic bacterial isolates were obtained by starch-agar plate method from municipal solid wastes. Six amylolytic bacteria were isolated and the best two isolates, named as DY and W1, were selected based on clear zone ratio. The 16S rDNA sequence analysis identified DY and W1 isolates as sp. and sp., respectively. Amylase production was optimized using basal media. The maximum level of amylase production was achieved from and isolates after 60 h and 48 h of cultivation, respectively. The optimal temperature, initial pH of the media, agitation and inoculum size were determined for the both isolates. Increased amylase production was observed when basal media were substituted with organic carbon and nitrogen sources. The optimum pH and temperature for amylase activity of the crude amylase of sp. were 5.0 and 50 °C, respectively and those of amylase from sp. were pH 7.0 and 50 °C, correspondingly. The crude amylase from the sp. was stable at pH 5.0-6.0 and up to 40 °C but that from sp. was stable at pH 7.0 and up to 30 °C. Amylases from both the isolates lost ∼50% activity when stored at room temperature for two days. Under the optimized fermentation conditions both and isolates produced almost the similar amount of amylase with organic kitchen wastes compared to the basal media. Results reported herein support the notion that sp. and sp. can be used to produce industrially important amylases by utilizing organic kitchen wastes.
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http://dx.doi.org/10.1016/j.jgeb.2017.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296612PMC
June 2017

Androgen receptor inhibitor-induced "BRCAness" and PARP inhibition are synthetically lethal for castration-resistant prostate cancer.

Sci Signal 2017 May 23;10(480). Epub 2017 May 23.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.

Cancers with loss-of-function mutations in or are deficient in the DNA damage repair pathway called homologous recombination (HR), rendering these cancers exquisitely vulnerable to poly(ADP-ribose) polymerase (PARP) inhibitors. This functional state and therapeutic sensitivity is referred to as "BRCAness" and is most commonly associated with some breast cancer types. Pharmaceutical induction of BRCAness could expand the use of PARP inhibitors to other tumor types. For example, mutations are present in only ~20% of prostate cancer patients. We found that castration-resistant prostate cancer (CRPC) cells showed increased expression of a set of HR-associated genes, including , , and Although androgen-targeted therapy is typically not effective in CRPC patients, the androgen receptor inhibitor enzalutamide suppressed the expression of those HR genes in CRPC cells, thus creating HR deficiency and BRCAness. A "lead-in" treatment strategy, in which enzalutamide was followed by the PARP inhibitor olaparib, promoted DNA damage-induced cell death and inhibited clonal proliferation of prostate cancer cells in culture and suppressed the growth of prostate cancer xenografts in mice. Thus, antiandrogen and PARP inhibitor combination therapy may be effective for CRPC patients and suggests that pharmaceutically inducing BRCAness may expand the clinical use of PARP inhibitors.
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http://dx.doi.org/10.1126/scisignal.aam7479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855082PMC
May 2017