Genome sequencing of captive white tigers from Bangladesh.

OBJECTIVES: The Bengal tiger Panthera tigris tigris, is an emblematic animal for Bangladesh. Despite being the apex predator in the wild, their number is decreasing due to anthropogenic activities such as hunting, urbanization, expansion of agriculture and deforestation. By contrast, captive tigers are flourishing due to practical conservation efforts. Breeding within the small captive population can produce inbreeding depression and genetic bottlenecks, which may limit the success of conservation efforts. Despite past decades of research, a comprehensive database on genetic variation in the captive and wild Bengal tigers in Bangladesh still needs to be included. Therefore, this research aimed to investigate the White Bengal tiger genome to create a resource for future studies to understand variation underlying important functional traits. DATA DESCRIPTION: Blood samples from Chattogram Zoo were collected for three white Bengal tigers. Genomic DNA for all collected samples were extracted using a commercial DNA extraction kit. Whole genome sequencing was performed using a DNBseq platform. We generated 77 Gb of whole-genome sequencing (WGS) data for three white Bengal tigers (Average 11X coverage/sample). The data we generated will establish a paradigm for tiger research in Bangladesh by providing a genomic resource for future functional studies on the Bengal white tiger.

A Brief Review on Recent Developments in Diels-Alder Reactions.

The [4+2] Diels-Alder cycloaddition has been widely used for the synthesis of six-mem-ber scaffolds. In recent years, there have been significant developments in this area, including the discovery and design of novel dienes and dienophiles with improved reactivity and selectivity. These new building blocks can be used to develop diverse molecular structures with functional group compatibility. Additionally, there is the use of catalytic systems and metal-mediated reactions to enable asymmetric [4+2] cycloadditions, resulting in enantiomerically enriched products. Over-all, recent studies related to [4+2] Diels-Alder cycloaddition using numerous dienes, dienophiles, and catalysts in different reaction conditions have significantly improved the efficiency, selectivity, and versatility of the reaction, making it an increasingly important tool in the synthesis of complex organic molecules as presented in this review. These advancements offer exciting possibilities for the development of new methods and reagents for the construction of six-membered rings and the synthesis of bioactive compounds.

Flavonoids as promising anticancer therapeutics: Contemporary research, nanoantioxidant potential, and future scope.

Flavonoids are natural polyphenolic compounds considered safe, pleiotropic, and readily available molecules. It is widely distributed in various food products such as fruits and vegetables and beverages such as green tea, wine, and coca-based products. Many studies have reported the anticancer potential of flavonoids against different types of cancers, including solid tumors. The chemopreventive effect of flavonoids is attributed to various mechanisms, including modulation of autophagy, induction of cell cycle arrest, apoptosis, and antioxidant defense. Despite of significant anticancer activity of flavonoids, their clinical translation is limited due to their poor biopharmaceutical attributes (such as low aqueous solubility, limited permeability across the biological membranes (intestinal and blood-brain barrier), and stability issue in biological systems). A nanoparticulate system is an approach that is widely utilized to improve the biopharmaceutical performance and therapeutic efficacy of phytopharmaceuticals. The present review discusses the significant anticancer potential of promising flavonoids in different cancers and the utilization of nanoparticulate systems to improve their nanoantioxidant activity further to enhance the anticancer activity of loaded promising flavonoids. Although, various plant-derived secondary metabolites including flavonoids have been recommended for treating cancer, further vigilant research is warranted to prove their translational values.

Bioactive Flavonoids: A Comparative Overview of the Biogenetic and Chemical Synthesis Approach.

Flavonoids are natural polyphenolic compounds and constitute a major class of plant secondary metabolites. To date, structures of more than 10,000 different flavonoids have been elucidated, and most of them are present in cells and tissues of plant parts. Flavonoids have been reported to exert multiple physiological activities and are also consumed as dietary supplements. Flavonoids have been extensively explored as anticancer, anti-inflammatory, antidiabetic, antirheumatic, antioxidant, antimalarial, neuroprotective, cardioprotective, anti-angiogenic, and antiproliferative agents. Most of the flavonoids are biosynthesized in plants via the phenylpropanoid pathway. However, they are associated with some limitations. Chemical synthesis is an alternative strategy to improve the yield and obtain purified products but is hampered by drawbacks, such as intolerance to stressful lab conditions. Pharmacokinetics is the rate-limiting step defining the bioavailability and metabolism of flavonoids, though greatly influenced by their chemical structure. However, nanoformulation is an emerging technique to improve biopharmaceutical fate and achieve target drug delivery. Thus, much attention should be given to identifying other possible chemical approaches for synthesizing flavonoids and improving their pharmacokinetic profiling, hence potentiating their efficacy in clinic.

Identification of polymorphisms in GDF9 and BMP15 genes in Jamunapari and crossbred goats in Bangladesh.

Polymorphisms in growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes have been found to be associated with litter size in goats across the globe. Our previous study detected single-nucleotide polymorphisms (SNPs) in GDF9 and BMP15 genes associated with litter size in Black Bengal, Bangladesh's primary native goat breed. However, Jamunapari and crossbred goats in Bangladesh are yet to be investigated for litter size-associated polymorphisms. In this study, we screened Jamunapari and crossbred (50% Black Bengal × 50% Jamunapari) goats to identify polymorphisms in the GDF9 and BMP15 genes and to assess the association between identified SNPs and litter size. The genomic DNA from 100 female goats (50 Jamunapari and 50 crossbred) was used in polymerase chain reactions (PCRs) to amplify exon 2 of the GDF9 and exon 2 of the BMP15 genes. PCR products were sequenced employing the BigDye Terminator cycle sequencing protocol to identify SNPs. We used a generalized linear model to perform the association analysis for identified SNPs and litter size. Seven SNPs were identified, of which four, C818CT, G1073A, G1189A, and G1330T, were in the GDF9 gene and three, G616T, G735A, and G811A, were in the BMP15 gene. G735A was a synonymous SNP, whereas the remaining were non-synonymous SNPs. Identified SNP loci in GDF9 were low polymorphic (PIC < 0.25), while loci in BMP15 were moderately polymorphic (PIC ≥ 0.25). The genotypes at the G1330T locus had a significant (p < 0.05) difference in litter size in Jamunapari goats, but no significant difference was observed for all genotypes at other loci. Therefore, the G1330T loci could be useful as a marker in marker-assisted selection for litter size traits in goats of Bangladesh.

Occurrence of Shiga toxin-producing Escherichia coli carrying antimicrobial resistance genes in sheep on smallholdings in Bangladesh.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) are zoonotic foodborne pathogens and a significant concern with the emergence of antibiotic resistance. Close human contact might have a higher chance of being transmitted to humans from sheep if the sheep population is a potential reservoir of antimicrobial-resistant STEC. Therefore, this study aimed to examine the sheep population in rural Bangladesh for antimicrobial-resistant STEC. METHODS: We screened 200 faecal samples collected from sheep in three Upazilas from the Chattogram district. Randomisation of sampling was not performed due to the smaller flock size (two to six animals per smallholding). Phenotypically positive E. coli isolates were examined for two Shiga toxin-producing genes - stx1 and stx2. PCR-positive STEC isolates were investigated for the presence of antimicrobial resistance (AMR) genes - blaTEM , sul1 and sul2. RESULTS: In total, 123 of the 200 tested samples were confirmed positive E. coli using culture-based methods. PCR results show 17 (13.8%) E. coli isolates harboured ≥ one virulent gene (stx1 or/and stx2) of STEC. The AMR profile of STEC isolates was determined utilising the disc diffusion method. Of the STEC isolates, 82, 76, 71 and 71% were susceptible to chloramphenicol, gentamicin, ciprofloxacin and ampicillin. In contrast, 47% of isolates were resistant to trimethoprim-sulfamethoxazole, and 41% were resistant to amoxicillin. In addition, six of the tested STEC isolates exhibited the blaTEM  gene; eight STEC isolates had the sul1 gene, and the sul2 gene was detected in ten STEC isolates. CONCLUSION: To our knowledge, this study is the first to reveal a substantial percentage of STEC isolated from sheep in rural Bangladesh harbouring AMR genes.

Application of nanotechnology to herbal antioxidants as improved phytomedicine: An expanding horizon.

Phytotherapy, based on medicinal plants, have excellent potential in managing several diseases. A vital part of the healthcare system is herbal medicines, consisting of therapeutic agents with high safety profile and no or least adverse effects. Herbs or medicinal plants show anticancer, antioxidant, and gene-protective activity, which is useful for pharmaceutical industries. In vitro, the extract of antioxidant compounds prevents the growth of colon and liver cancer cells, followed by a dose-dependent method. The screening of extracts is done by using in vitro models. Reactive oxygen species (ROS) and free radicals lead to diseases based on age which promotes oxidative stress. Different types of ROSs available have central roles in the normal physiology and functioning of processes. Herbal or traditional plant medicines have rich antioxidant activity. Despite the limited literature on the health effect of herbal extract or spices. There are many studies examining the encouraging health effects of single phytochemicals instigating from the medicinal plant. This review provides a detailed overview on herbal antioxidants and how application of nanotechnology can improve its biological activity in managing several major diseases, and having no reported side effects.

Natural compounds as safe therapeutic options for ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Several conventional treatments for UC such as corticosteroids, immunosuppressive agents, tumor necrosis factor antagonist, integrin blockers, and interleukin antagonist, and salicylates are available but are associated with the various limitations and side-effects. None of the above treatments helps to achieve the ultimate goal of the therapy, i.e., maintenance of remission in the long-term. Natural remedies for the treatment of UC show comparatively less side effects as compared to conventional approaches, and affordable. The current review presents details on the role of herbal drugs in the treatment and cure of UC. Google, PubMed, Web of Science, and Scopus portals have been searched for potentially relevant literature to get the latest developments and updated information related to use of natural drugs in the treatment of UC. Natural products have been used over centuries to treat UC. Some of the essential herbal constituents exhibiting antiulcerogenic activity include gymnemic acid (Gymnema sylvestre), shagoal (Zingiber officinale), catechin (Camellia sinensis), curcumin (Curcuma longa), arctigenin (Arctium lappa), and boswellic acid (Boswellia serrata). Although many plant-derived products have been recommended for UC, further research to understand the exact molecular mechanism is still warranted to establish their usefulness clinically.

Sweet pepper and its principle constituent capsiate: functional properties and health benefits.

Capsiate is a non-pungent analogue of capsaicin. It belongs to the family of capsinoids which are esters of vanillyl alcohol with fatty acids while capsaicin belongs to the family of capsaicinoids that are amides of vanillylamine with a variety of branched-chain fatty acids. While capsaicin is extensively reported for plethora of pharmacological actions, capsiate remains much less explored. Extracted from various species of Capsicum plant, the molecule has also been chemically synthesized via a number of synthetic and enzymatic routes. Based on its action on transient receptor potential vanilloid subfamily member 1 receptors, recent research has focused on its potential roles in treatment of obesity, metabolic disorders, cancer, cardiovascular disorders and gastro-intestinal disorders. Its toxicity profile has been reported to be much safe. The molecule, however, faces the challenge of low aqueous solubility and stability. It has been commercialized for its use as a weight loss supplement. However, the therapeutic potential of the compound which is much beyond boosting metabolism remains unexplored hitherto. This comprehensive review summarizes the studies demonstrating the therapeutic potential of capsiate in various pathological conditions. Discussed also are potential future directions for formulation strategies to develop efficient, safe and cost-effective dosage forms of capsiate to explore its role in various disease conditions. The databases investigated include Cochrane library, Medline, Embase, Pubmed and in-house databases. The search terms were "capsiate," "capsinoids," "thermogenesis," and their combinations. The articles were screened for relevance by going through their abstract. All the articles pertaining to physicochemical, physiological, pharmacological and therapeutic effects of capsiate have been included in the manuscript.

Anti-ulcerogenic effect of methanolic extract of Elaeagnus conferta Roxb. seeds in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant. AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta. MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied. RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner. CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

Polymorphism of fecundity genes (BMP15 and GDF9) and their association with litter size in Bangladeshi prolific Black Bengal goat.

Goat farming in Bangladesh is primarily centred on indigenous Black Bengal goat, a highly prolific breed. Searching for genetic markers associated with prolificacy in this breed is vital for the country's goat breeding industry. However, there are no reports on polymorphisms associated with the fertility of Bangladeshi Black Bengal goats. This study investigated two major fecundity genes-bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) to detect any possible mutations in these two genes associated with litter size in Black Bengal goats. Blood samples were collected from 40 raised goats in Hathazari Government Goat Farm, Bangladesh. Genomic DNA was extracted; PCR amplification was performed; and sequencing of PCR products was performed to detect polymorphism loci in the target genes. Five SNPs viz. C735A, C743A, G754T, C781A and C808G were detected in exon 2 of BMP15 gene. A SNP (T1173A) was detected in GDF9 exon 2. Association results show that SNPs at the 735, 754 and 781 nucleotide positions of BMP15 exon 2 had a significant association with litter size in Black Bengal goat. The effect of parity was also highly significant (P < 0.001) on litter size. For the first time, this study explored SNP loci in fecundity genes in Bangladeshi prolific Black Bengal goats. Further studies with many genetically unrelated animals for assessing the association of these loci and others in the fecundity genes with litter size may be useful.

The Why, Where, Who, How, and What of the vesicular delivery systems.

Though vesicular delivery systems have been widely explored and reviewed, no comprehensive review exists that covers their development from the inception of the concept to its culmination in the form of regulated marketed formulations. With the advancement of scientific research in the field of nanomedicine, certain category of vesicular delivery systems have successfully reached the global market. Despite extensive research and highly encouraging results in a plethora of pathological conditions in the preclinical studies, translation of these nanomedicines from laboratory to market has been very limited. Aim of this review is to describe comprehensively the various colloidal delivery systems, focusing mainly on their conventional and advanced methods of preparation, different characterization techniques and main success stories of their journey from bench to bedside of the patient. The review also touches the finer nuances of the use of modern formulation approach of DoE (Design of Experiments) in their formulation and the status of regulatory guidelines for the approval of these nanomedicines.

Occurrence of Escherichia coli carrying Shiga toxin-producing genes in buffaloes on smallholdings in Bangladesh.

BACKGROUND AND AIM: Shiga toxin-producing Escherichia coli (STEC) has emerged as significant foodborne pathogens. Ruminants are the primary reservoir of the zoonotic STEC. In Bangladesh, previous studies reported the presence of STEC in cattle, goat, and sheep; however, there is little information about STEC carriage by buffaloes. This study aimed to determine the occurrence of STEC in healthy (absence of clinical signs and symptoms) buffaloes on smallholdings in Bangladesh and to assess the antimicrobial resistance pattern of identified STEC isolates. MATERIALS AND METHODS: A total of 100 rectal swab samples were obtained from randomly selected buffaloes on 40 smallholdings in Chittagong Division, Bangladesh. Samples were subjected to bacteriological screening to identify E. coli. All E. coli isolates were examined for the presence of the Shiga toxin-producing genes - Shiga toxin 1 (stx1) and Shiga toxin 2 (stx2) using polymerase chain reaction. The antimicrobial susceptibility of identified STEC isolates was tested using the disk diffusion method. RESULTS: Results show that 71 fecal samples were positive for E. coli in bacteriological screening. The proportion of buffaloes harboring STEC isolates was 11% (11/100) (95% confidence interval [CI] 6.1-18.8], of which 7% (7/100) (95% CI 3.2-13.9) and 4% (4/100) (95% CI 1.2-10.2) carried stx1 and stx2 genes, respectively. Antibiogram revealed that 91% (10/11), 73% (8/11), 55% (6/11), and 55% (6/11) STEC isolates were resistant to tetracycline, sulfamethoxazole-trimethoprim, erythromycin, and ampicillin, respectively. In contrast, 91% (10/11) STEC isolates were sensitive to ciprofloxacin, chloramphenicol, and gentamicin, whereas 73% (8/11) isolates were sensitive to ceftriaxone. CONCLUSION: This study highlights, for the first time, a significant proportion of fecal samples from healthy buffaloes on smallholdings in Bangladesh harboring antimicrobial-resistant STEC. Transmission of antimicrobial-resistant STEC from buffaloes to humans could pose an added risk to public health in rural Bangladesh.

Sub-chronic safety evaluation of aqueous extract of Alangium salvifolium (L.f.) Wangerin leaves in rats.

Conventionally, the juice and extract of Alangium salvifolium leaves have been used for the treatment of diabetes, wound healing, dog bite, and as a poultice in rheumatism. To carry out the sub-chronic toxicity and thereafter safety evaluation of A. salvifolium leaves. The aqueous extract of A. salvifolium leaves was administered orally at the doses of 200, 400, and 800 mg/kg/day for 90 days. All the animals were observed daily for general behavior, changes in body weight, food, and water consumption. At the end of the treatment period, biochemical and hematological parameters were analyzed; and the animals were sacrificed for histopathological examination of heart, lungs, liver, and kidney. The general behavior and water intake were normal in all the rats. The increase in body weight was observed in female rats of all the groups while body weight was decreased in high dose group animals of both sexes. Hematological parameters were not disturbed by the continuous use of extract. A significant decrease in glucose level was observed in intermediate- and high-dose group animals while urea and creatinine level were significantly high in animals of high-dose group. Although histopathological examination of most of the organs exhibited no structural changes, some tubal damage in kidneys was observed in high-dose group animals. The high dose of extract has shown mild signs of toxicity on kidney function test, but no toxic response was observed on hematological and liver biochemical parameters. The extract also exhibited hypoglycemic potential.

Solubility and solution stability studies of different amino acid prodrugs of bromhexine.

OBJECTIVE: The aim of the present study was to prepare the amino acid prodrugs of bromhexine hydrochloride to improve its solubility. METHODS: All the prodrugs were synthesized by first reacting bromhexine with tert-butoxycarbonyl (Boc) protected amino acid and then deprotection was carried out by using trifluoroacetic acid. These prodrugs were characterized by their melting points, NMR, mass and FTIR spectroscopy. Solubility and partition coefficient of bromhexine and various prodrugs were determined. The solution stability of various prodrugs was also determined in various buffers of pH ranging from 2 to 10. Degradation rate constants and half-life were also determined at various pH. RESULTS AND DISCUSSION: The structures of all the synthesized prodrugs were confirmed by NMR, mass and FTIR spectra. The prodrug 2-N-L-alanyl-bromhexine hydrochloride showed maximum solubility and minimum partition coefficient value. These prodrugs may hydrolyze by one or more mechanisms. The order of decreasing rates of hydrolysis was 2-N-L-prolyl-bromhexine hydrochloride > 2-N-glycyl-bromhexine hydrochloride > 2-N-L-alanyl-bromhexine hydrochloride. All the prodrugs exhibited maximum stability in the acidic pH range and undergo base catalyzed hydrolysis. CONCLUSION: Solubility studies and partition coefficient values indicated that the synthesized prodrug, 2-N-L-alanyl-bromhexine hydrochloride, was least lipophilic as compared to other synthesized prodrugs. Solution stability studies showed that this prodrug undergo minimum hydrolysis at 37°C. So, it is concluded that 2-N-L-alanyl-bromhexine hydrochloride exhibits better solubility and stability as compared to other synthesized prodrugs.

Inhibitors of inosine monophosphate dehydrogenase: probes for antiviral drug discovery.

The role of inosine monophosphate dehydrogenase (IMPDH) at the metabolic branch point of de novo purine nucleotide biosynthesis makes this enzyme an attractive probe for the discovery of antiviral compounds. Introduction of unsaturation at the 2-position of IMP, the natural substrate for IMPDH, produces Michael acceptors at that position, which results in these compounds being inhibitors of IMPDH. Consistent with this mechanism-based molecular design, some of the parent nucleosides exhibited antiviral activity.

New frontiers in proteomics research: a perspective.

Substantial advances have been made in the fundamental understanding of human biology, ranging from DNA structure to identification of diseases associated with genetic abnormalities. Genome sequence information is becoming available in unprecedented amounts. The absence of a direct functional correlation between gene transcripts and their corresponding proteins, however, represents a significant roadblock for improving the efficiency of biological discoveries. The success of proteomics depends on the ability to identify and analyze protein products in a cell or tissue and, this is reliant on the application of several key technologies. Proteomics is in its exponential growth phase. Two-dimensional electrophoresis complemented with mass spectrometry provides a global view of the state of the proteins from the sample. Proteins identification is a requirement to understand their functional diversity. Subtle difference in protein structure and function can contribute to complexity and diversity of life. This review focuses on the progress and the applications of proteomics science with special reference to integration of the evolving technologies involved to address biological questions.