Search

SARS-CoV-2, a deadly coronavirus sparked COVID-19 pandemic around the globe. With an increased mutation rate, this infectious agent is highly transmissible inducing an escalated rate of infections and death everywhere. Hence, the discovery of a viable antiviral therapy option is urgent. Computational approaches have offered a revolutionary framework to identify novel antimicrobial treatment regimens and allow a quicker, cost-effective, and productive conversion into the health center by evaluating preliminary and safety investigations. The primary purpose of this research was to find plausible plant-derived antiviral small molecules to halt the viral entrance into individuals by clogging the adherence of Spike protein with human ACE2 receptor and to suppress their genome replication by obstructing the activity of Nsp3 (Nonstructural protein 3) and 3CLpro (main protease). An in-house library of 1163 phytochemicals were selected from the NPASS and PubChem databases for downstream analysis. Preliminary analysis with SwissADME and pkCSM revealed 149 finest small molecules from the large dataset. Virtual screening using the molecular docking scoring and the MM-GBSA data analysis revealed that three candidate ligands CHEMBL503 (Lovastatin), CHEMBL490355 (Sulfuretin), and CHEMBL4216332 (Grayanoside A) successfully formed docked complex within the active site of human ACE2 receptor, Nsp3, and 3CLpro, respectively. Dual method molecular dynamics (MD) simulation and post-MD MM-GBSA further confirmed efficient binding and stable interaction between the ligands and target proteins. Furthermore, biological activity spectra and molecular target analysis revealed that all three preselected phytochemicals were biologically active and safe for human use. Throughout the adopted methodology, all three therapeutic candidates significantly outperformed the control drugs (Molnupiravir and Paxlovid). Finally, our research implies that these SARS-CoV-2 protein antagonists might be viable therapeutic options. At the same time, enough wet lab evaluations would be needed to ensure the therapeutic potency of the recommended drug candidates for SARS-CoV-2.

It is crucial to monitor the microbial ambience in heavy metal enriched industrial effluents that generally discharge into the environment. Therefore, the present study aimed to understand the load of heavy metals in multidrug-resistant lactose fermenting microorganisms isolating from textile industry effluents. Samples were collected from five different textile industrial canals. In most of the cases, the colony forming units (CFUs) per plate were uncountable at 10-6 dilution but countable at 10-10 dilution. A total of 100 lactose fermenting (LF) isolates were selected using 4 differential media and tested for the determination of minimum inhibitory concentrations (MICs) of heavy metals and antibiotic susceptibility. For nickel (Ni), the MIC was 0.3 mM for almost 98% isolates. The MIC was 0.5 mM for chromium (Cr) in almost 99% isolates. For lead (Pb), 100% isolates had a MIC of 0.4 mM. The most prevalent (36%) resistance pattern was found for sulfamethoxazole-trimethoprim (SXT) and only 10% isolates showed resistance to cefotaxime (CTX). The combined effect of heavy metals and antibiotics revealed that in most cases, the antibiotic zone of inhibition was increased. Plasmid profiling showed that among 14 selective isolates, high sized (21kb) plasmid was found in 6 isolates. Key words: Antibiotics, effluents, heavy metals, minimum inhibitory concentration (MIC), antimicrobial resistance.

Mankind is facing an unprecedented threat of existence due to the antibiotic resistance developed by bacteria. The unripe fruits of Diospyros malabarica (Desr.) Kostel. (family: Ebenaceae) can be considered as one of the natural sources to tackle this issue. The present study is designed to assess the antimicrobial activity of D. malabarica seed and flesh ex-tracts. Herein, D. malabarica extracts were prepared using polar solvents (i.e., water and 70% ethanol) and their antimicrobial activity as well as in vivo toxicity was investigated. Their antibacterial activity was investigated against gram positive (Bacillus subtilis) and gram negative (Escherichia coli DH5α, and Salmonella typhi) bacteria at different time points. All the extracts showed the highest antibacterial activity after 2 hours of incubation. The aqueous seed extract showed the maximum zone of inhibition (i.e., ~13 mm) against Bacillus subtilis with a minimum inhibitory concentration (MIC) value of 2 μg/μl. The an-tibacterial propensity was also confirmed through trypan blue dye exclusion assay, CellToxTM Green assay, and lipid peroxidation (LPO) assay. On the other hand, the etha-nolic seed extract demonstrated higher antifungal activity through inhibition of mycelial growth. All the extracts showed excellent hemocompatibility against both human and rat red blood cells (RBCs). They also did not show any toxicity to rat liver and kidneys. Taken together, this study demonstrates that the aqueous and ethanolic extracts of D. malabarica seed and flesh could be an effective source of natural antimicrobial agents with no cytotox-ic activity.

Among metallic nanoparticles, silver nanoparticles (AgNPs) have a wide spectrum of medical applications. Herein, biogenic silver nanoparticles (bAgNPs) were prepared from extracts of Caesalpinia di...

Cobalt ferrite nanoparticle (CFN) has received attention in magnetic resonance imaging (MRI) as a promising contrast agent due to its higher saturation magnetization and magneto-crystalline anisotr...

Nanotherapeutics has emerged as the most sought after approach to tackle the menace of drug-resistant pathogenic bacteria. Among others, biogenic silver nanoparticles (bAgNPs) synthesized using medicinal plant extracts demonstrate promising antibacterial propensity with excellent biocompatibility. Herein, bAgNPs were synthesized through the green chemistry approach using

Among metallic nanoparticles, silver nanoparticles (AgNPs) have a wide spectrum of medical applications. Herein, biogenic silver nanoparticles (bAgNPs) were prepared from extracts of

Antiphospholipid antibodies are highly prevalent in autoimmune diseases and mainly associated with thromboembolic events, which is one of the major reasons for cancer-related mortality. Confirmed adult cancer patients were included (n = 40) with an equal number of age- and sex-matched healthy controls. The presence and concentration of anticardiolipin antibodies were investigated by the enzyme-linked immunosorbent assay using the venous blood samples. aCL antibodies were detected in 60.0% (n = 24) of the cancer patients compared to none in the healthy controls (p < 0.001). The serum concentration of aCL antibodies was significantly higher in cancer patients than controls (p < 0.001) and ranged from 89.0 U/mL to 133.0 U/mL among the aCL-positive patients. All the lung cancer patients (n = 6) were diagnosed with positive aCL, and a borderline significant association of aCL antibody positivity was observed in colon cancer patients (p = 0.051). About 72.7% of the advanced-stage cancer individuals and 81.8% of the cancer patients who underwent surgery were diagnosed with positive aCL antibodies. A significant association of aCL antibody positivity was observed with cancer patients comorbid with heart diseases (p = 0.005). The prevalence and serum levels of aCL antibodies were significantly higher in cancer patients compared to healthy controls. Cancer patients (i.e., lung, liver, and colon), at advanced-stage, comorbid with heart diseases, who underwent surgery, were more likely to be diagnosed with aCL antibodies.

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder among women of reproductive age. PCOS is characterized by ovulatory dysfunction, clinical or biochemical features of hyperandrogenism, and polycystic ovaries. The risk of cancer among PCOS patients has been a topic of discussion for decades due to the overlapping metabolic and endocrine abnormalities. This review article focuses on the association of PCOS with various types of reproductive (such as endometrial cancer, ovarian cancer, and breast cancer) and non-reproductive cancers, considering different aspects, such as the risk of cancer progression in PCOS patients, the underlying factors, and the mechanism through which PCOS might progress to cancer. The information provided in this article would help create awareness among PCOS patients about the need to take risk-reducing measures. This article might also aid in the effort of identifying novel therapeutic targets to counteract the progression of cancer in PCOS.

Fabrication of hybrid hydrogels to improve biological properties or to decrease the disadvantages of biomaterials has been a popular approach. With the background of snowballing threat of skin wound to public health and economy, this study was undertaken utilizing xanthan gum (Xnt), citric acid (C), gelatin (Gel), glutaraldehyde (G) and HPLC-grade water to fabricate a series of composite hydrogels i.e. Xnt, Xnt:C, Xnt:Gel(3):G, Xnt:C:Gel(3):G, Xnt:Gel(5):G, Xnt:C:Gel(5):G for investigating their wound healing efficacy in experimental rat skin wound model. Physicochemical characterization revealed that all the composite hydrogels contained more than 90% water. The hydrogels displayed swelling ability, biodegradability, good polymeric networks and porosity. Fourier Transform Infrared Spectroscopy (FT-IR) studies confirmed the presence of bound water and free, intra and inter molecular bound hydrogen bonded OH and NH in the hydrogels. All the hydrogels showed significant wound healing potency in experimental deep second degree skin burns in rats compared to controls. 20 days post-application of hydrogels, Xnt:Gel(3):G, Xnt:Gel(5):G and Xnt:C:Gel(5):G-treated wounds showed better recovery compared to other composite hydrogels. The highest wound contraction of these hydrogel composites might be due to presence of Gel in the formulations. We conclude that, Xnt:Gel(3):G, Xnt:Gel(5):G and Xnt:C:Gel(5):G might be effective wound dressing material.

not availableJahangirnagar University J. Biol. Sci. 5(2): 57-60, 2016 (December)

In Bangladesh, goat farming is substantially hampered due to outbreaks of respiratory infectious diseases like pneumonia causing morbidity, mortality and economic losses in Black Bengal goats. Among the infectious agents, Pasteurella maltocida is more frequently associated with the outbreak of acute pneumonia and death of goats. Hence, the occurrence of P. multocida in the goat population should be regularly investigated to effectively control the disease. Furthermore, antibiotic resistance/sensitivity profiling of P. maltocida also needs to be regularly updated for designing or updating of efficient treatment strategy. In this investigation, 150 nasal swab samples from goats were collected from Savar region of Bangladesh and on the basis of colony, staining and biochemical characteristics P. multocida were isolated in 25 samples. Disc diffusion assay was used to determine the antimicrobial susceptibility of 20 isolates against 9 different antimicrobial agents. This study revealed that the rate of P. multocida isolated from goats in Savar area was about 16.67%. The incidence of P. multocida was higher in goats affected with acute pneumonia than apparently healthy goats. P. multocida was fully resistant to penicillin and amoxicillin whereas showed high sensitivity towards ciprofloxacin followed by streptomycin and neomycin. This study suggests that ciprofloxacin, streptomycin and neomycin are potent anti-Pasteurella multocida drugs.

The devastating outbreak of COVID-19 has spread all over the world and has become a global health concern. There is no specific therapeutics to encounter the COVID-19. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control human viral infections employing post-transcriptional gene silencing (PTGS) through neutralizing target complementary mRNA. RNA-dependent RNA polymerase (RdRp) encoded by the viral RdRp gene as a part of the replication-transcription complex can be adopted as an acceptable target for controlling SARS-CoV-2 mediated infection. Therefore, in the current study, accessible siRNA designing tools, including significant algorithms and parameters, were rationally used to design the candidate siRNAs against SARS-COV-2 encoded RdRp. The designed siRNA molecules possessed adequate nucleotide-based and other features for potent gene silencing. The targets of the designed siRNAs revealed no significant matches within the whole human genome, ruling out any possibilities for off-target silencing by the siRNAs. Characterization with different potential parameters of efficacy allowed selecting the finest siRNA among all the designed siRNA molecules. Further, validation assessment and target site accessibility prediction also rationalized the suitability of this siRNA molecule. Molecular docking study between the selected siRNA molecule and component of RNA interference (RNAi) pathway gave an excellent outcome. Molecular dynamics of two complexes: siRNA and argonaute complex, guide RNA, and target protein complex, have shown structural stability of these proteins. Therefore, the designed siRNA molecule might act as an effective therapeutic agent against the SARS-CoV-2 at the genome level and can prevent further outbreaks of COVID-19 in humans.

Objective: The study was undertaken with an objective to determine the seroprevalence of Peste des Petits Ruminants (PPR) in goats of different age groups. Materials and methods: A total of 606 goats (414 vaccinated and 192 unvaccinated) were randomly selected from Rajshahi, Sirajganj and Gazipur districts. The goats were categorized into different age gropus; (i) 0-6 months, (ii) 12-24 months, and (iii) >24 months. Blood samples were collected from the goats and sera were prepared. The sera were examined for the presence of antibodies against PPR virus (PPRV) by competitive enzyme linked immunosorbent assay (c-ELISA). Results: In the unvaccinated goats, overall seroprevalence was 8.70% (n=36/414). The highest seroprevalence was recorded in Rajshahi (28.57%; n=18/63) which was followed by Gazipur (16%; n=12/75) and Sirajganj (2.17%; n=6/276). The age-based overall seroprevalence in the unvaccinated samples from 0-6 months age group was 9.43% (n=15/159). Similarly, 12-24 and >24 months age groups of goats revealed the presence of 6% (n=9/150) and 11.43% (n=12/105) seroprevalence against PPRV. Of the vaccinated samples, overall 76.04% (n=146/192) were seropositive against PPRV. Within the age group of 0-6 months, vaccinated samples had the highest seroprevalence (80.25%; n=65/81) as compared to 12-24 (70.83%; n=34/48) and >24 months (74.60%; n=47/63) age groups of goats, respectively. Conclusion: The seroprevalence in the unvaccinated samples indicates that PPRV is circulating in Bangladesh which is inducing to produce natural antibody in goats. This study also states that the field level vaccination against PPRV could give protection to the goats. http://doi.org/10.5455/javar.2016.c140

Extracellular nicotinamide adenine dinucleotide (NAD) cleaving activity of a particular cell type determines the rate of the degradation of extracellular NAD with formation of metabolites in the vicinity of the plasma membrane, which has important physiological consequences. It is yet to be elucidated whether intact human neutrophils have any extracellular NAD cleaving activity. In this study, with a simple fluorometric assay utilizing 1,N(6)-ethenoadenine dinucleotide (etheno-NAD) as the substrate, we have shown that intact peripheral human neutrophils have scant extracellular etheno-NAD cleaving activity, which is much less than that of mouse bone marrow neutrophils, mouse peripheral neutrophils, human monocytes and lymphocytes. With high performance liquid chromatography (HPLC), we have identified that ADP-ribose (ADPR) is the major extracellular metabolite of NAD degradation by intact human neutrophils. The scant extracellular etheno-NAD cleaving activity is decreased further by N-formyl-methionine-leucine-phenylalanine (fMLP), a chemoattractant for neutrophils. The fMLP-mediated decrease in the extracellular etheno-NAD cleaving activity is reversed by WRW4, a potent FPRL1 antagonist. These findings show that a much less extracellular etheno-NAD cleaving activity of intact human neutrophils compared to other immune cell types is down-regulated by fMLP via a low affinity fMLP receptor FPRL1.

BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer’s disease (AD); intracerebroventricular injection of β-amyloid peptide (Aβ) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Aβ1-42 until evaluation) effectively blocked Aβ1-42-induced impairment in passive avoidance performance, and Aβ1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1α in the hippocampus. In addition, it alleviated the Aβ1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1β in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.

With the background of snowballing threat of skin wound to public health and economy, this study was undertaken utilizing xanthan gum (Xnt), citric acid (C), gelatin (Gel), glutaraldehyde (G) and HPLC-grade water to fabricate a series of composite hydrogels i.e. Xnt, Xnt:C, Xnt:Gel(3):G, Xnt:C:Gel(3):G, Xnt:Gel(5):G, Xnt:C:Gel(5):G for investigating their wound healing efficacy in experimental rat skin wound model. Physicochemical characterization revealed that all the composite hydrogels contained more than 90% water. The hydrogels displayed swelling ability, biodegradability, good polymeric networks and porosity. Fourier Transform Infrared Spectroscopy (FT-IR) studies confirmed the presence of bound water and free, intra and inter molecular bound hydrogen bonded OH and NH in the hydrogels. All the hydrogels showed significant wound healing potency in experimental deep second degree skin burns in rats compared to controls. 20 days post-application of hydrogels, Xnt:Gel(3):G, Xnt:Gel(5):G and Xnt:C:Gel(5):G-treated wounds showed better recovery compared to other composite hydrogels. We conclude that, Xnt:Gel(3):G, Xnt:Gel(5):G and Xnt:C:Gel(5):G might be effective wound dressing material.

We previously reported the protective effects of long-term administration of ferulic acid against the in vivo toxicity of β-amyloid peptide administered intracerebroventricularly in mice. In the present study, we investigated the effects of ferulic acid in transgenic amyloid precursor protein (APP)swe/presenilin 1 (PS1)dE9 (APP/PS1) mouse model of Alzheimer disease (AD). Chronic (for 6 months from the age of 6 to 12 months) oral administration of ferulic acid at a dose of 5.3 mg/kg/day significantly enhanced the performance in novel-object recognition task, and reduced amyloid deposition and interleukin-1 beta (IL-1β) levels in the frontal cortex. These results suggest that ferulic acid at a certain dosage could be useful for prevention and treatment of AD.

The tumor suppressor gene TP53 (p53) maintains genome stability. Mutation or loss of p53 is found in most cancers. Analysis of evolutionary constrains and p53 mutations reveal important sites for concomitant functional studies. In this study, phylogenetic analyses of the coding sequences of p53 from 26 mammals were carried out by applying a maximum likelihood method. The results display two branches under adaptive evolution in mammals. Moreover, each codon of p53 was analyzed by the PAML method for presence of positively selected sites. PAML identified several statistically significant amino acids that undergo positive selection. The data indicates that amino acids responsible for the core functions of p53 are highly conserved, while positively selected sites are predominantly located in the N- and C-terminus of p53. Further analysis of evolutionary pressure and mutations showed the occurrence of more frequent tumorigenic mutations in purifying sites of p53.

N-acetyl-L-cysteine (NAC) and cysteine have been implicated in a number of human neutrophils' functional responses. However, though Ca(2+) signaling is one of the key signalings contributing to the functional responses of human neutrophils, effects of NAC and cysteine on intracellular calcium concentration ([Ca(2+)]i) in human neutrophils have not been investigated yet. Thus, this study was carried out with an objective to investigate the effects of NAC and cysteine on [Ca(2+)]i in human neutrophils. We observed that NAC (1 µM ~ 1 mM) and cysteine (10 µM ~ 1 mM) increased [Ca(2+)]i in human neutrophils in a concentration-dependent manner. In NAC pre-supplmented buffer, an additive effect on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced increase in [Ca(2+)]i in human neutrophils was observed. In Ca(2+)-free buffer, NAC- and cysteine-induced [Ca(2+)]i increase in human neutrophils completely disappeared, suggesting that NAC- and cysteine-mediated increase in [Ca(2+)]i in human neutrophils occur through Ca(2+) influx. NAC- and cysteine-induced [Ca(2+)]i increase was effectively inhibited by calcium channel inhibitors SKF96365 (10 µM) and ruthenium red (20 µM). In Na(+)-free HEPES, both NAC and cysteine induced a marked increase in [Ca(2+)]i in human neutrophils, arguing against the possibility that Na(+)-dependent intracellular uptake of NAC and cysteine is necessary for their [Ca(2+)]i increasing activity. Our results show that NAC and cysteine induce [Ca(2+)]i increase through Ca(2+) influx in human neutrophils via SKF96365- and ruthenium red-dependent way.