This paper aims at characterizing the longitudinal and temporal variability of tidal flows in the Gorai-Pussur River system of Bangladesh, which spans about 158 km, starting from Bordia upstream to ...Akram Point downstream. Considering the upstream fresh water discharge and the downstream tide level as the drivers of tidal flow variability, the spatiotemporal change in hydrodynamics of the Pussur Fluvial Estuary was simulated using HEC-RAS software at the neap-spring and seasonal scales. The model was calibrated by comparing the simulated discharge and water levels with available measured data at an intermediate station. During the dry season, the tidal effect from the sea reaches Bordia, while in the monsoon season, the tide reaches about 15 km less (up to Kalia) due to the increased flow of freshwater. The Pussur river experiences tidal amplification up to Chalna, located approximately 90 km from its mouth. Beyond Chalna, tidal dumping covers a distance of 100–170 km upto Bordia. The tidal range ratio between Akram Point and Mongla is 1.28. The phase shift of the high water is found approximately 1.0 h over a distance of 50 km. It is found that due to 50% increase of discharge in Bordia, the increase of discharges at Kalia and Chalna were found as 43% and 7%, respectively. For a 0.5 m increase in water level at downstream (Akram Point), the high and low water levels at Chalna are increased by 0.15 and 0.69 m, while for 1.0 m increase in water level at downstream, the high and low water levels at Chalna are increased by 0.67 and 1.20 m, respectively.
The perception of social support among patients with advanced diseases is influenced by various factors. The socio-cultural context of Bangladesh significantly shapes the experience of patients with ...advanced cancer and their perception of social support. This study's aim was to assess the perceived social support by these patients and investigate the factors that shape their perception. This cross-sectional study was conducted among 115 advanced cancer patients admitted to the palliative medicine department of a tertiary care hospital in Bangladesh. Perceived social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS). Perceived social support was moderate to high for most (74.7%) of the participants. The majority (97.4%) perceived moderate to high level of support from their families. The lowest level of support was perceived from friends (53%). Factors such as economic status, family size, companionship of children, and emotional support from spouses influenced the level of perceived social support. Social support is one of the important aspects of palliative care. Identifying the factors influencing the perception of social support among cancer patients is essential for palliative care professionals to effectively address their care needs.The perception of social support among patients with advanced diseases is influenced by various factors. The socio-cultural context of Bangladesh significantly shapes the experience of patients with advanced cancer and their perception of social support. This study's aim was to assess the perceived social support by these patients and investigate the factors that shape their perception. This cross-sectional study was conducted among 115 advanced cancer patients admitted to the palliative medicine department of a tertiary care hospital in Bangladesh. Perceived social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS). Perceived social support was moderate to high for most (74.7%) of the participants. The majority (97.4%) perceived moderate to high level of support from their families. The lowest level of support was perceived from friends (53%). Factors such as economic status, family size, companionship of children, and emotional support from spouses influenced the level of perceived social support. Social support is one of the important aspects of palliative care. Identifying the factors influencing the perception of social support among cancer patients is essential for palliative care professionals to effectively address their care needs.
Cancer is one of the leading causes of mortality globally. To cope with cancer, it is necessary to develop anticancer drugs. Bioactive natural products, i.e. diarylheptanoids, have gained significant ...attention of researchers owing to their intriguing structures and potent biological activities. In this article, considering the development of anticancer drugs with enhanced selectivity towards cancerous cells, a series of Cyclic Diarylheptanoids (CDHs) are designed, synthesized and evaluated their biological activity.
To establish an easy route for the synthesis of diarylheptanoids, and evaluate their antiproliferative, and topoisomerase-I & -IIα inhibitory activities, for developing potential anticancer drugs among CDHs.
Diarylheptanoids were synthesized from reported linear diarylheptanoids using the classical Ullmann reaction. Antibacterial activity was evaluated by the filter paper disc diffusion method. Cell viability was assessed by measuring mitochondrial dehydrogenase activity with a Cell Counting Kit (CCK-8). Topoisomerases I and II (topo-I and -IIα) inhibitory activity was measured by the assessment of relaxation of supercoiled pBR322 plasmid DNA. IFD protocol of Schrodinger Maestro v11.1 was used to characterize the binding pattern of studied compounds with the ATPase domain of the human topo-IIα.
The synthesized CDHs were evaluated for their biological activities (antibacterial, antiproliferative, and topoisomerase-I & -IIα inhibitory activities, respectively). Leading to obtain a series of anticancer agents with the least inhibitory activities against different microbes, improving their selectivity for cancer cells. In brief, most of the synthesized CDHs had excellent antiproliferative activity against T47D (human breast cancer cell line). Pterocarine possessed the strongest activity (2i; IC50 = 0.63µM) against T47D. The cyclic diarylheptanoid 2b induced 30% inhibition of topoisomerase-IIα activity at 100μM compared with the reference of etoposide, which induced 72% inhibition. Among the tested compounds, galeon (2h) displayed very low activity against four bacterial strains. Compounds 2b, 2h, and 2i formed hydrogen bonds with Thr215, Asn91, Asn120, Ala167, Lys168 and Ile141 residues, which are important for binding of ligand compound to the ATPase binding site of topoisomerase IIα by acting as ATP competitive molecule validated by docking study. In silico Absorption, Distribution, Metabolism and Excretion (ADME) analysis revealed the predicted ADME parameters of the studied compounds which showed recommended values.
A series of CDHs were synthesized and evaluated for their antibacterial, antiproliferative, and topo-I & -IIα inhibitory activities. SARs study, molecular docking study and in silico ADME analysis were conducted. Five compounds exhibited excellent and selective antiproliferative activity against the human breast cancer cell line (T47D). Among them, a compound 2h showed topo-IIα activity by 30% at 100µM, which represented a moderate intensity of inhibition compared with etoposide. Three of them formed hydrogen bonds with Thr215, Asn91, Asn120, and Ala167 residues, which are considered as crucial residues for binding to the ATPase domain of topoisomerase IIα. According to in silico drug-likeness property analysis, three compounds are expected to show superiority over etoposide in case of absorption, distribution, metabolism and excretion.
In Inflammatory Bowel Disease (IBD), malabsorption of electrolytes (NaCl) results in diarrhea. Inhibition of coupled NaCl absorption, mediated by the dual operation of Na:H and Cl:HCO
exchangers on ...the brush border membrane (BBM) of the intestinal villus cells has been reported in IBD. In the SAMP1/YitFcs (SAMP1) mice model of spontaneous ileitis, representing Crohn's disease, DRA (Downregulated in Adenoma) mediated Cl:HCO
exchange was shown to be inhibited secondary to diminished affinity of the exchanger for Cl. However, NHE3 mediated Na:H exchange remained unaffected. Mast cells and their secreted mediators are known to be increased in the IBD mucosa and can affect intestinal electrolyte absorption. However, how mast cell mediators may regulate Cl:HCO
exchange in SAMP1 mice is unknown. Therefore, the aim of this study was to determine the effect of mast cell mediators on the downregulation of DRA in SAMP1 mice. Mast cell numbers and their degranulation marker enzyme (β-hexosaminidase) levels were significantly increased in SAMP1 mice compared to control AKR mice. However, treatment of SAMP1 mice with a mast cell stabilizer, ketotifen, restored the β-hexosaminidase enzyme levels to normal in the intestine, demonstrating stabilization of mast cells by ketotifen. Moreover, downregulation of Cl:HCO
exchange activity was restored in ketotifen treated SAMP1 mice. Kinetic studies showed that ketotifen restored the altered affinity of Cl:HCO
exchange in SAMP1 mice villus cells thus reinstating its activity to normal. Further, RT-qPCR, Western blot and immunofluorescence studies showed that the expression levels of DRA mRNA and BBM protein, respectively remained unaltered in all experimental conditions, supporting the kinetic data. Thus, inhibition of Cl:HCO
exchange resulting in chloride malabsorption leading to diarrhea in IBD is likely mediated by mast cell mediators.
Hepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly ...understood. We compared the genetic relatedness and virulence associated mutations of endemic HEV strains with outbreak strains. We analyzed systematically collected serum samples from HEV immunoglobulin M (IgM) positive patients attended at Bangabandhu Sheikh Mujib Medical University, Dhaka from August 2013 to June 2015. HEV RNA positive samples were subjected to whole genome sequencing. Genotype and subtype of the strains were determined by phylogenetic analysis. Virulence associated mutations e.g. acute viral hepatitis (AVH), fulminant hepatic failure (FHF), chronic hepatitis, ribavirin treatment failure (RTF), B and T cell neutralization epitopes were determined. 92 HEV immunoglobulin M (IgM) antibody positive plasma samples (43 in 2013-2014 and 49 in 2014-2015) were studied. 77.1% (70/92) of the samples were HEV RNA positive. A 279 bp open reading frame (ORF) 2 and ORF 3 sequence was obtained from 54.2% (38/70) of the strains. Of these 38 strains, whole genome sequence (WGS) was obtained from 21 strains. In phylogenetic analysis of 38 (279 bp) sequence all HEV sequences belonged to genotype 1 and subtype 1a. Further phylogenetic analysis of 21 HEV WGS, Bangladeshi HEV sequences clustered with genotype 1a sequences from neighboring countries. Within genotype 1a cluster, Bangladesh HEV strains formed a separate cluster with the 2010 HEV outbreak strains from northern Bangladesh. 80.9 to 100% of the strains had A317T, T735I, L1120I, L1110F, P259S, V1479I, G1634K mutations associates AVH, FHF and RTF. Mutations in T cell recognition epitope T3, T5, T7 was observed in 76.1%, 100% and 100% of the strains respectively. Strains of HEV genotype 1a are dominant in Bangladesh and are associated with endemic and outbreak of HEV infection. HEV isolates in Bangladesh have high prevalence of virulence associated mutations and mutation which alters antigenicity to B and T cell epitopes.
Obesity increases the risk of postmenopausal breast cancer (BC). This risk is mediated by obesity-induced changes in the adipose-derived secretome (ADS). The pathogenesis of BC in obesity is ...stimulated by mTOR hyperactivity. In obesity, leucine might support mTOR hyperactivity. Leucine uptake by BC cells is through L-Type Amino Acid Transporter 1 (LAT1). Our objective was to link obesity-ADS induction of LAT1 to the induction of mTOR signaling. Lean- and obese-ADS were obtained from lean and obese mice, respectively. Breast ADS was obtained from BC patients. Estrogen-receptor-positive BC cells were stimulated with ADS. LAT1 activity was determined by uptake of
H-leucine. The LAT1/CD98 complex, and mTOR signaling were assayed by Western blot. The LAT1 antagonists, BCH and JPH203, were used to inhibit LAT1. Cell migration and invasion were measured by Transwell assays. The results showed obese-ADS-induced LAT1 activity by increasing transporter affinity for leucine. Consistent with this mechanism, LAT1 and CD98 expression were unchanged. Induction of mTOR by obese-ADS was inhibited by LAT1 antagonists. Breast ADS from patients with BMIs > 30 stimulated BC cell migration and invasiveness. Collectively, our findings show that obese-ADS induction of LAT1 supports mTOR hyperactivity in luminal BC cells.
In an effort to develop improved and effective targeted tyrosine kinase inhibitors (TKIs), a series of twelve novel compounds with the structural motif ...“(E)-4-(((1H-benzodimidazol-2-yl)methyl)amino)-N′-(halogenated)benzylidenebenzohydrazide” were successfully synthesized in three steps, yielding high product yields (53–97%). Among this new class of compounds, 6c and 6h-j exhibited excellent cytotoxic effects against four different cancer cell lines, with half-maximal inhibitory concentration (IC50) values ranging from 7.82 to 21.48 μM. Notably, compounds 6h and 6i emerged as the most potent inhibitors, demonstrating significant activity against key kinases such as EGFR, HER2, and CDK2. Furthermore, compound 6h displayed potent inhibitory activity against AURKC, while 6i showed potent inhibitory effects against the mTOR enzyme, with excellent IC50 values comparable with well-established TKIs. The mechanistic study of lead compound 6i revealed its ability to induce cell cycle arrest and apoptosis in HepG2 liver cancer cells. This was accompanied by upregulation of pro-apoptotic caspase-3 and Bax and downregulation of anti-apoptotic Bcl-2. Additionally, molecular docking studies indicated that the binding interactions of compounds 6h and 6i with the target enzymes give multiple interactions. These results underscore the ability of compound 6i as a compelling lead candidate warranting further optimization and development as a potent multi-targeted kinase inhibitor, which could have significant implications for the treatment of various cancers. The detailed structural optimization, mechanism of action, and in vivo evaluation of this class of compounds warrant further investigation to assess their therapeutic potential.
Gastrointestinal polyps are considered to be the precursors of cancer development in most of the cases. Therefore, early detection and removal of polyps can reduce the possibility of cancer. Video ...endoscopy is the most used diagnostic modality for gastrointestinal polyps. But, because it is an operator dependent procedure, several human factors can lead to misdetection of polyps. Computer aided polyp detection can reduce polyp miss detection rate and assists doctors in finding the most important regions to pay attention to. In this paper, an automatic system has been proposed as a support to gastrointestinal polyp detection. This system captures the video streams from endoscopic video and, in the output, it shows the identified polyps. Color wavelet (CW) features and convolutional neural network (CNN) features of video frames are extracted and combined together which are used to train a linear support vector machine (SVM). Evaluations on standard public databases show that the proposed system outperforms the state-of-the-art methods, gaining accuracy of 98.65%, sensitivity of 98.79%, and specificity of 98.52%.
•The presence of cations highly influence CO2/brine IFT.•Interfacial tension of CO2/formation brine exceeds IFT of CO2/NaCl brine.•An underestimation of CO2/brine IFT is reported in the ...literature.•Using only NaCl brine leads to overestimation of CO2 that can be stored.•A longer time is needed to reach equilibrium when bivalent salts are present.
Carbon dioxide (CO2) geo-storage in deep saline aquifers is a promising technique to mitigate anthropogenic emissions and achieve net-zero targets. The storage capacity and containment security of CO2 in subsurface systems are influenced by a range of processes, including geochemical and interfacial interactions between rock/CO2/brine and CO2/brine systems. Specifically, CO2/brine interfacial tension (IFT) directly affects capillary sealing efficiency and CO2 storage volume. Accurate characterization of IFT under realistic subsurface conditions, i.e., pressure, temperature, salinity, and formation brine composition, is thus vital to predict storage capacity and ensure containment security. Here we report new data sets of CO2/brine IFT obtained by the pendant drop method under a pressure range of 0–20 MPa at three different temperatures 298 K, 323 K and 343 K, and for three different solutions: fresh water, 21.4 wt% NaCl brine and 21.4 wt% formation brine comprising of mixed salt from a real field in the Middle East. Moreover, a detailed analysis is performed for the factors influencing IFT. Importantly, we also provide insights into the key experimental artifacts pertinent to the IFT phenomena e.g., the impact of CO2/water equilibrium on IFT. For all systems, IFT exhibits a monotonically decreasing trend with pressure until it reaches a plateau at ∼ 12 MPa, after which it stabilizes upon a critical pressure called angular point. The system IFT vs. temperature trend exhibits a monotonic increase throughout the studied experimental matrix. The lowest recorded IFT is 22.8 mN/m at 20 MPa and 298 K while the highest recorded IFT is 78.92 mN/m at 0.1 MPa and 298 K. Similarly, IFT also increases steadily when formation brine contains monovalent and divalent ions, while bivalent cations have a greater influence on IFT compared to monovalent cations. Notably, at the same salinity, temperature and pressure conditions, the CO2/brine systems IFT, on average, is greater for formation brine than synthetic NaCl brine. Importantly, we also present the effects of mixed salts on CO2 saturation and the associated storage capacity using core flooding experiments. It was found that CO2 saturation records 38 % in the NaCl saturated core while it reaches 22 % in the formation brine saturated core. The results of this study thus provide new datasets and insights into the interfacial phenomena relevant to subsurface CO2 storage applications.
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