The inositol-requiring enzyme 1 (IRE1) endoplasmic reticulum stress pathway promotes MDA-MB-231 cell survival and renewal in response to the aryl-ureido fatty acid CTU.

Current treatment options for triple-negative breast cancer (TNBC) are limited to toxic drug combinations of low efficacy. We recently identified an aryl-substituted fatty acid analogue, termed CTU, that effectively killed TNBC cells in vitro and in mouse xenograft models in vivo without producing toxicity. However, there was a residual cell population that survived treatment. The present study evaluated the mechanisms that underlie survival and renewal in CTU-treated MDA-MB-231 TNBC cells. RNA-seq profiling identified several pro-inflammatory signaling pathways that were activated in treated cells. Increased expression of cyclooxygenase-2 and the cytokines IL-6, IL-8 and GM-CSF was confirmed by real-time RT-PCR, ELISA and Western blot analysis. Increased self-renewal was confirmed using the non-adherent, in vitro colony-forming mammosphere assay. Neutralizing antibodies to IL-6, IL-8 and GM-CSF, as well as cyclooxygenase-2 inhibition suppressed the self-renewal of MDA-MB-231 cells post-CTU treatment. IPA network analysis identified major NF-κB and XBP1 gene networks that were activated by CTU; chemical inhibitors of these pathways and esiRNA knock-down decreased the production of pro-inflammatory mediators. NF-κB and XBP1 signaling was in turn activated by the endoplasmic reticulum (ER)-stress sensor inositol-requiring enzyme 1 (IRE1), which mediates the unfolded protein response. Co-treatment with an inhibitor of IRE1 kinase and RNase activities, decreased phospho-NF-κB and XBP1s expression and the production of pro-inflammatory mediators. Further, IRE1 inhibition also enhanced apoptotic cell death and prevented the activation of self-renewal by CTU. Taken together, the present findings indicate that the IRE1 ER-stress pathway is activated by the anti-cancer lipid analogue CTU, which then activates secondary self-renewal in TNBC cells.

Fine conductive line printing of high viscosity CuO ink using near field electrospinning (NFES).

Modern printed electronics applications require patterning of fine conductive lines of sufficient thickness. However, the two requirements for pattern width and thickness are a trade-off. To print fine pattern at a micrometer size, the nozzle diameter must be approximately the size of the pattern width, so only low-viscosity inks are used. As a result, the pattern is likely to be very thin and multiple overlapping printing is required for sufficient conductance. In order to use high viscosity ink for fine patterning, near field electrospinning (NFES) is attracting attention because it can print very thin and thick patterns using large nozzles (high-viscosity ink). Until now, silver paste ink has been used for microconductive patterning using electrospinning. However, Ag nanoparticle (NP) inks are expensive. In this study, we report the use of a relatively inexpensive CuO NP ink for electrospinning-based printing. For implementation, the material preparation, printing and post-processing process are discussed. For post-processing, a continuous wave (CW) green laser with a 532 nm wavelength was used to reduce the CuO to Cu and sinter the nanoparticles. After sintering, the 50 µm width and 1.48 µm thick Cu conductive line exhibited a resistivity of 5.46 µΩ·cm, which is 3.25 times of the bulk resistivity of Cu.

Inclusion of the in-chain sulfur in 3-thiaCTU increases the efficiency of mitochondrial targeting and cell killing by anticancer aryl-urea fatty acids.

Mitochondria in tumor cells are functionally different from those in normal cells and could be targeted to develop new anticancer agents. We showed recently that the aryl-ureido fatty acid CTU is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells by increasing the production of reactive oxygen species (ROS), activating endoplasmic reticulum (ER)-stress and promoting apoptosis. However, prolonged treatment with high doses of CTU were required for in vivo anti-tumor activity. Thus, new strategies are now required to produce agents that have enhanced anticancer activity over CTU. In the present study we prepared a novel aryl-urea termed 3-thiaCTU, that contained an in-chain sulfur heteroatom, for evaluation in tumor cell lines and in mice carrying tumor xenografts. The principal finding to emerge was that 3-thiaCTU was several-fold more active than CTU in the activation of aryl-urea mechanisms that promoted cancer cell killing. Thus, in in vitro studies 3-thiaCTU disrupted the mitochondrial membrane potential, increased ROS production, activated ER-stress and promoted tumor cell apoptosis more effectively than CTU. 3-ThiaCTU was also significantly more active than CTUin vivo in mice that carried MDA-MB-231 cell xenografts. Compared to CTU, 3-thiaCTU prevented tumor growth more effectively and at much lower doses. These findings indicate that, in comparison to CTU, 3-thiaCTU is an aryl-urea with markedly enhanced activity that could now be suitable for development as a novel anticancer agent.

Spatial association of Aedes aegypti with dengue fever hotspots in an endemic region.

Background and objective: Dengue is a vector-borne viral disease usually transmitted by Aedes mosquitoes. Around the world, the relationship between local vector density and frequency of dengue cases is being explored and needs further evidence. This study aimed to analyze the potential spatial relationships between the dengue vector (Aedes aegypti) and dengue cases in the megacity of Bangladesh during the 2019 dengue outbreak. Methods: Vector density measures were used to estimate spatial associations with dengue case distribution. Location was determined for 364 dengue cases who were admitted to Dhaka Medical College Hospital over a period of 4 months. Data were collected using a semi-structured questionnaire, and prior consent was ensured before participation. The Moran global index, Getis-Ord Gi∗, ordinary least squares regression, geographically weighted regression and count data regression methods were used for spatial analysis. Results: We found that dengue case distribution was not associated with immature Aedes aegypti mosquito (larvae) density across the city. The relationship between larval density measured by the Breteau Index (BI) and House Index (HI) with dengue cases was nonstationary and not statistically significant. Conclusion: The location of dengue cases appears to be unrelated to vector distribution and vector density. These findings should prompt the search for other transmission risk factors.

The ixabepilone and vandetanib combination shows synergistic activity in docetaxel-resistant MDA-MB-231 breast cancer cells.

BACKGROUND: The lack of drug targets is an obstacle to the treatment of patients with triple-negative breast cancer (TNBC). At present, non-specific cytotoxic drugs are first-line agents, but the development of resistance is a major problem with these agents. The epidermal growth factor receptor (EGFR) is a potential target in some TNBCs, because its tyrosine kinase activity drives tumorigenesis. Thus, small molecule inhibitors of the EGFR in combination with cytotoxic agents could be important for the treatment of TNBCs. METHODS: The present study evaluated the efficacies of clinically approved EGFR inhibitors in combination with the cytotoxic agent ixabepilone in parental and docetaxel-resistant MDA-MB-231 cells (231C and TXT cells, respectively). Cell viability was assessed using MTT reduction assays, cell death pathways were evaluated using annexin V/7-aminoactinomycin D staining and flow cytometry and Western immunoblotting was used to assess the expression of pro- and anti-apoptotic proteins in cells. RESULTS: Ixabepilone and the EGFR inhibitors gefitinib and vandetanib inhibited 231C and TXT cell proliferation, but the alternate EGFR inhibitors erlotinib and lapatinib were poorly active. Using combination analysis, ixabepilone/vandetanib was synergistic in both cell types, whereas the ixabepilone/gefitinib combination exhibited antagonism. By flow cytometry, ixabepilone/vandetanib enhanced 231C and TXT cell death over that produced by the single agents and also enhanced caspase-3 cleavage and the pro/anti-apoptotic Bcl-2 protein ratios over ixabepilone alone. CONCLUSIONS: These findings suggest that the ixabepilone/vandetanib combination may have promise for the treatment of patients with drug-resistant TNBC.

Preclinical Evaluation of Ixabepilone in Combination with VEGF Receptor and PARP Inhibitors in Taxane-Sensitive and Taxane-Resistant MDA-MB-231 Breast Cancer Cells.

Long-term use of cytotoxic agents promotes drug-resistance in triple-negative breast cancer (TNBC). The identification of new drug combinations with efficacy against drug-resistant TNBC cells in vitro is valuable in developing new clinical strategies to produce further cancer remissions. We undertook combination analysis of the cytotoxic agent ixabepilone with small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and poly (ADP-ribose) polymerase (PARP) in taxane-sensitive (231C) and taxane-resistant (TXT) MDA-MB-231-derived cells. As single agents, the VEGFR inhibitors cediranib and bosutinib decreased both 231C and TXT cell viability, but four other VEGFR inhibitors and two PARP inhibitors were less effective. Combinations of ixabepilone with either cediranib or bosutinib synergistically decreased 231C cell viability. However, only the ixabepilone/cediranib combination was synergistic in TXT cells, with predicted 15.3-fold and 1.65-fold clinical dose reductions for ixabepilone and cediranib, respectively. Flow cytometry and immunoblotting were used to further evaluate the loss of cell viability. Thus, TXT cell killing by ixabepilone/cediranib was enhanced over ixabepilone alone, and expression of proapoptotic cleaved caspase-3 and the Bak/Bcl-2 protein ratio were increased. These findings suggest that the synergistic activity of the ixabepilone/cediranib combination in taxane-sensitive and taxane-resistant cells may warrant clinical evaluation in TNBC patients.

The aryl-ureido fatty acid CTU activates endoplasmic reticulum stress and PERK/NOXA-mediated apoptosis in tumor cells by a dual mitochondrial-targeting mechanism.

The cancer cell mitochondrion is functionally different from that in normal cells and could be targeted to develop novel experimental therapeutics. The aryl-ureido fatty acid CTU (16({[4-chloro-3-(trifluoromethyl)phenyl]-carbamoyl}amino)hexadecanoic acid) is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells. Here we show that CTU rapidly depolarized the inner mitochondrial membrane, selectively inhibited complex III of the electron transport chain and increased reactive oxygen species (ROS) production. From RNA-seq analysis, endoplasmic reticulum (ER)-stress was a major activated pathway in CTU-treated cells and in MDA-MB-231 tumor xenografts from CTU-treated nu/nu mice. Mitochondrion-derived ROS activated the PERK-linked ER-stress pathway and induced the BH3-only protein NOXA leading to outer mitochondrial membrane (OMM) disruption. The lipid peroxyl scavenger α-tocopherol attenuated CTU-dependent ER-stress and apoptosis which confirmed the critical role of ROS. Oleic acid protected against CTU-mediated apoptosis by activating Mcl-1 expression, which increased NOXA sequestration and prevented OMM disruption. Taken together, CTU both uncouples mitochondrial electron transport and activates ROS production which promotes ER-stress-dependent OMM disruption and tumor cell death. Dual-mitochondrial targeting agents like CTU offer a novel approach for development of new anti-cancer therapeutics.

Nutrition and Food Security in Bangladesh: Achievements, Challenges, and Impact of the COVID-19 Pandemic.

BACKGROUND: Bangladesh has experienced remarkable transformation in demographic, health, and nutritional status of the population. The changes have exposed the population to a number of challenges, the detrimental effect of which on health and nutrition is likely to be increased by the coronavirus disease 2019 (COVID-19) pandemic. We provide an overview of health and nutritional challenges in Bangladesh in relation to demographic transition and the COVID-19 pandemic. METHODS: We identified and reviewed recent reports, published articles, and pertinent gray literature on nutrition and food security in Bangladesh to provide historical and contextual information. RESULTS: The review identifies the progress as well as existing burden regarding nutrition and food security in Bangladesh and highlights the challenges in the coming days in regard to population growth and the COVID-19 pandemic. The country is on track to reduce all forms of childhood undernutrition, while the proportion of nutrition-related noncommunicable diseases is rising owing to changes in dietary intake, low physical activity, and sedentary lifestyle. CONCLUSIONS: Despite remarkable progress, health and nutritional status of the population in Bangladesh faces challenges, particularly in relation to demographic transition and compounded by the COVID-19 pandemic, which require concerted attention from policymakers as well as stakeholders.

High-Efficiency Electrospray Deposition Method for Nonconductive Substrates: Applications of Superhydrophobic Coatings.

When highly insulating materials are used as substrates for electronic devices, manufacturing yields become worse, and electronic components are often damaged due to undissipated electrostatic charges on such substrates. In the case of electrospray deposition, the problem of undissipated charges is particularly vexing. If charges accumulated on the substrate are not properly compensated, a repulsive force is generated against the incoming charged droplets, which negatively affects the uniformity and deposition rate of the coating layer. In order to overcome this limitation, we demonstrated a new electrospray method, which can significantly increase the deposition efficiency even in the presence of accumulated charges on nonconductive substrates. A highly reliable superhydrophobic layer was uniformly deposited on highly insulating substrates, including printed circuit board (PCB), polyester (PET), and polyimide (PI) substrates.

Megacities as drivers of national outbreaks: The 2017 chikungunya outbreak in Dhaka, Bangladesh.

BACKGROUND: Several large outbreaks of chikungunya have been reported in the Indian Ocean region in the last decade. In 2017, an outbreak occurred in Dhaka, Bangladesh, one of the largest and densest megacities in the world. Population mobility and fluctuations in population density are important drivers of epidemics. Measuring population mobility during outbreaks is challenging but is a particularly important goal in the context of rapidly growing and highly connected cities in low- and middle-income countries, which can act to amplify and spread local epidemics nationally and internationally. METHODS: We first describe the epidemiology of the 2017 chikungunya outbreak in Dhaka and estimate incidence using a mechanistic model of chikungunya transmission parametrized with epidemiological data from a household survey. We combine the modeled dynamics of chikungunya in Dhaka, with mobility estimates derived from mobile phone data for over 4 million subscribers, to understand the role of population mobility on the spatial spread of chikungunya within and outside Dhaka during the 2017 outbreak. RESULTS: We estimate a much higher incidence of chikungunya in Dhaka than suggested by official case counts. Vector abundance, local demographics, and population mobility were associated with spatial heterogeneities in incidence in Dhaka. The peak of the outbreak in Dhaka coincided with the annual Eid holidays, during which large numbers of people traveled from Dhaka to other parts of the country. We show that travel during Eid likely resulted in the spread of the infection to the rest of the country. CONCLUSIONS: Our results highlight the impact of large-scale population movements, for example during holidays, on the spread of infectious diseases. These dynamics are difficult to capture using traditional approaches, and we compare our results to a standard diffusion model, to highlight the value of real-time data from mobile phones for outbreak analysis, forecasting, and surveillance.

Studying the effects of profenofos, an endocrine disruptor, on organogenesis of zebrafish.

Profenofos is an endocrine-disrupting chemical that can enter into the aquatic ecosystem either through surface runoff or through percolation of a toxicant from the soil. In order to clarify the effect of profenofos on the developmental stages of zebrafish, the embryos were treated with serial dilutions of profenofos (0%, 10%, 25%, and 50% of LC50). Embryos were treated with profenofos for 7 days or until hatching. The toxic endpoints assessed include hatching time, survival, malformation, and heartbeats of the embryos. In a 96-h test on zebrafish embryos, the LC50 of profenofos was 0.057 mg/L. Profenofos considerably lowered survival, increased abnormalities at different ontogenetic stages, and developed malformations of different organs in a concentration-dependent fashion. The identified developmental malformations were fluid accumulation, impaired jaw, short tail, ruptured pectoral and caudal fin, curved body, thin yolk sac tube, and deformed heart. The way of looping arrangement of the heart at the early stage of embryos was significantly influenced by the higher concentration of profenofos. Heartbeat is also reduced significantly in a concentration-dependent fashion. The results show that the zebrafish are susceptible to profenofos even at lower concentrations in the initial stage. Therefore, when used in agricultural areas adjacent to the aquatic environment, endocrine-disrupting chemicals should be used in an appropriate manner.

Three-dimensional surface printing method for interconnecting electrodes on opposite sides of substrates.

As the application of the direct printing method becomes diversified, printing on substrates with non-flat surfaces is increasingly required. However, printing on three-dimensional surfaces suffers from a number of difficulties, which include ink flow due to gravity, and the connection of print lines over sharp edges. This study presents an effective way to print a fine pattern (~ 30 µm) on three different faces with sharp edge boundaries. The method uses a deflectable and stretchable jet stream of conductive ink, which is produced by near-field electrospinning (NFES) technique. Due to added polymer in the ink, the jet stream from the nozzle is less likely to be disconnected, even when it is deposited over sharp edges of objects. As a practical industrial application, we demonstrate that the method can be effectively used for recent display applications, which require the connection of electrical signal and power on both sides of the glass. When the total length of printed lines along the 'Π' shaped glass surfaces was 1.2 mm, we could achieve the average resistance of 0.84 Ω.

Modulation of Sirt1/NF-κB interaction of evogliptin is attributed to inhibition of vascular inflammatory response leading to attenuation of atherosclerotic plaque formation.

Evogliptin is a novel, potent and selective dipeptidyl peptidase 4 inhibitor that has received approval for use in the treatment of type 2 diabetes in South Korea. In the management of diabetes, it is important to reduce cardiovascular risk factors, as this can decrease the complication and mortality rate. However, the effect of evogliptin on the atherosclerotic progression has not been evaluated. In this study, we examined the effects of evogliptin on the progression of atherosclerosis and its possible mechanism of action. The anti-atherosclerotic effect of evogliptin was evaluated in ApoE-knockout mice fed high-fat diet analysed by plaque lesion formation, lipid profiles and vascular inflammatory response in the atherosclerotic progression. The in vitro effects of evogliptin were verified in endothelial cells analysed by immunoblotting, siRNA gene knockdown, promoter-luciferase assay, immunoprecipitation and adhesion assay. Evogliptin reduced the high-fat diet-induced atherosclerotic plaque area in the ApoE-/- mouse model. Macrophage infiltration into lesions was suppressed in the evogliptin group. In the endothelial cells, evogliptin inhibited inflammatory responses via suppression of adhesion molecules induced by TNF-α. TNF-α-mediated activation of NF-κB was ameliorated by evogliptin via the interaction of NF-κB with SIRT1 (Sirtuin-1). TNF-α-mediated adhesion between endothelial cells and monocytes was inhibited by evogliptin, but this inhibitory effect was reversed by Sirt1 gene knockdown. This study demonstrates that the protective effect of evogliptin on atherosclerotic progression via inhibition of vascular inflammation. The findings imply that evogliptin has potential for anti-atherosclerosis therapy that targets arterial inflammation.

Aryl-urea fatty acids that activate the p38 MAP kinase and down-regulate multiple cyclins decrease the viability of MDA-MB-231 breast cancer cells.

We recently developed a novel aryl-urea fatty acid (CTU; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that impaired the viability of MDA-MB-231 breast cancer cells in vitro and in mouse xenograft models in vivo. At present there is a deficiency of information on the structural requirements for the activity of CTU. Our initial study suggested that electron withdrawing groups were required on the aryl ring, and in this study we further evaluated the influence of the electronic properties of aromatic substitution on the capacity of CTU analogues to decrease MDA-MB-231 breast cancer cell viability. Analogues that contained strong electron-withdrawing groups in the meta- and para-positions of the aryl ring exhibited improved activity over CTU. Effective analogues down-regulated the cyclins D1, E1 and B1, and the cyclin-dependent kinases (CDKs) 4 and 6, that form complexes to coordinate cell cycle progression. Active CTU analogues also stimulated the phosphorylation and activation of the p38 MAP kinase signalling pathway in cells and both decreased proliferation (5-bromo-2'-deoxyuridine (brdU) incorporation) and activated apoptosis (executioner caspase-3/7 activity). These agents offer a new approach to target the cell cycle at multiple phases in order to efficiently prevent cancer cell expansion. Inclusion of the present structural information in drug design approaches could enhance the development of optimal analogues of aryl-urea fatty acids as potential anti-cancer agents.

The Red Alga Gracilariopsis chorda and Its Active Constituent Arachidonic Acid Promote Spine Dynamics via Dendritic Filopodia and Potentiate Functional Synaptic Plasticity in Hippocampal Neurons.

Exogenous neurotrophins can induce neuronal differentiation, outgrowth, survival, and synaptic function in the central nervous system. In primary cultures of rat hippocampal neurons, an ethanol extract of the red alga Gracilariopsis chorda (GCE) and its active compound arachidonic acid (AA) significantly increased the densities of dendritic filopodia and spines, promoted the expression of presynaptic vesicle protein 2 (SV2) and postsynaptic density protein 95 (PSD-95), induced robust synaptogenesis, and increased the expression of cell division control protein 42 (CDC42) and actin-related protein 2 (ARP2), which are important for actin organization in dendritic protrusions, and facilitated presynaptic plasticity by increasing the size of the synaptic vesicle pool at presynaptic nerve terminals. In addition, oral administration of GCE and AA for 10 days, at concentrations of 1 mg/g and 2.2 µg/g body weight, respectively, significantly protected against scopolamine-induced memory impairment in mice by increasing the latency time in the passive avoidance test. These results provide strong scientific evidence that these natural products can be used as neurotrophic substances and/or dietary supplements for the prevention and treatment of memory-related neurological disorders via the reconstruction of axo-dendrites and its synapses.

Aberrations of the peripheral erythrocytes and its recovery patterns in a freshwater teleost, silver barb exposed to profenofos.

The present experiment was conducted to explicate the genotoxic effects of profenofos, an organophosphate insecticide, on the erythrocytes of silver barb (Barbonymus gonionotus). Silver barb were exposed to a solution of 10% and 50% of lethal concentrations (LC50) of profenofos as sub-lethal concentrations at different days (1, 7, 15, and 30 d), along with a control (0% profenofos). Subsequent recovery patterns were assessed allowing the fish exposed to profenofos free water for the same period that they were exposed to profenofos. Our results revealed that with the progression of time and concentration, fish exposed to profenofos showed significantly (p < .05) higher level of erythrocytic nuclear abnormalities (ENA) such as micronuclei, bi-nuclei, degenerated nuclei, notched nuclei, nuclear bridge and nuclear buds, as well as erythrocytic cellular abnormalities (ECA) such as echinocytic, elongated, fusion, spindle, tear-drop and twin shaped cells. After exposure, the silver barb recovered spontaneously, and the abnormal erythrocytic parameters were normalized with a concentration- and duration-dependent fashion. Therefore, these abnormalities and their recovery can be used to assess the toxic levels of pesticides on aquatic organisms. There is great potential to use this technique as in vivo to predict susceptibility of aquatic animals to environmental pollution.

Acute exposure to a quinalphos containing insecticide (convoy) causes genetic damage and nuclear changes in peripheral erythrocytes of silver barb, Barbonymus gonionotus.

The present study was aimed to assess the genotoxic effect in fish caused by convoy, an insecticide commercial formulation containing quinalphos, present in the aquatic waterbody. For this purpose a freshwater teleost, silver barb was exposed to sublethal concentrations (25% and 50% of LC50) of convoy and erythrocytic cellular abnormalities (ECA) and erythrocytic nuclear abnormalities (ENA) tests were performed in addition to the commonly used micronucleus (MN) assay using peripheral erythrocytes and DNA contents in the different tissues after 1, 24, 36, 48, and 72 h of exposures. The obtained results indicated that acute exposure of different sub lethal concentrations of convoy to the fish resulted in significant alterations of erythrocytes as well as significant reduction of DNA contents in blood and vital organs and tissues, such as the brain, liver, kidney and muscle. Compared to each treatment excluding control group, frequencies of ECA, ENA, and MN were found to be elevated with exposure time of the doses. From this study, we conclude that convoy is a hazardous chemical to silver barb. Bioassays can be used as a tool for screening aquatic pollution, especially for insecticides.

A Distinctive Pattern of Beauveria bassiana-biotransformed Ginsenoside Products Triggers Mitochondria/FasL-mediated Apoptosis in Colon Cancer Cells.

Ginseng is one of the most commonly used adaptogens. Transformation into the minor ginsenosides produces compounds with more effective action. Beauveria bassiana, a teleomorph of Cordyceps bassiana, is a highly efficient producer of mammalian steroids and produces large amounts of sugar-utilizing enzymes. However, the fermentation of steroid glycosides in ginseng with B. bassiana has never been studied. Thus, we evaluated the bioconversion of the major ginsenosides in white ginseng by B. bassiana. Interestingly, B. bassiana increased the total amount of protopanaxadiols and hydrolyzed Rb1 into minor ginsenosides, exhibiting high levels of Rd and Rg3, as well as moderate levels of Rb2 and Rc analyzed by high-performance liquid chromatography coupled with evaporative light-scattering detection. The ß-glucosidase activity was highly increased, which led to the selective elimination of sugar moiety at the 20-C position of Rb1 to Rd, followed by Rg3. Rb2 and Rc accumulated because of the minimal activities of α-L-arabinopyranosidase and α-L-arabinofuranosidase, respectively. The fermentation product exerted dose-dependent cytotoxicity in HCT-15 cells, which are resistant to ginseng. The product, but not white ginseng, exhibited apoptotic effects via the Fas ligand and caspase 8/9. This study demonstrates for the first time that the B. bassiana-fermented metabolites have potent apoptotic activity in colon cancer cells, linking to a therapeutic use.

Study on Liver Dysfunction in Type 2 Diabetic Patients in Bangladesh.

AIM: Diabetes mellitus (DM) represents one of the major lifestyle-related pathological conditions; the incidence and prevalence of DM have reached an epidemic level around the world. Diabetes mellitus is usually associated with obesity, coronary diseases, and cerebral pathologies. However, more insights are required to evaluate a temporal relation between DM and hepatic functions. This study assesses whether and to what extent liver functions are modified in DM patients. MATERIALS AND METHODS: A total of 100 patients with type 2 DM and 100 normal healthy controls were enrolled in this study following proper scrutiny of inclusion and exclusion criteria. Different parameters of liver function tests were measured in patients in the two groups. Data were analyzed to assess the extent and magnitude of abnormal liver functions in DM. RESULTS: The levels of bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, and prothrombin time were 0.737 ± 0.311 mg/dL, 39.00 ± 24.21 IU/L, 26.42 ± 10.40 IU/L, 4.10 ± 0.513 g/dL, and 16.46 ± 2.78 seconds in patients with DM and 0.506 ± 0.183 mg/dL, 28.26 ± 6.67 IU/L, 18.90 ± 4.75 IU/L, 4.12 ± 0.277 g/dL, and 14.23 ± 1.04 seconds in control subjects. Statistical analyses revealed that most of these parameters of liver function test were significantly different in DM patients compared to control subjects (p < 0.05). Serum alkaline phosphatase level was 89.61 ± 25.59 mg/dL in type 2 DM patients and 96.83 ± 16.34 mg/dL in control subjects (p > 0.05). The prevalence of abnormal values of serum bilirubin, ALT, AST, prothrombin time, and albumin were 5.17, 31.03, 5.17, 5.17, 43.10, and 10.34% respectively in type 2 DM patients and 0, 2, 0, 2, 3, and 0% respectively in control subjects, indicating high prevalence of DM patients with abnormal liver functions. CONCLUSION: Abnormal liver functions of different extents and magnitudes have been found in type 2 DM patients, and the impact of abnormal liver function should be considered during the management of DM patients and also to assess their long-term follow-up prognosis. HOW TO CITE THIS ARTICLE: Rashid MHO, Haque MZ, Rahman MK, Khan MMR, Rahman ASMM, Al-Mahtab M, Rahman MS, Roy PK, Islam MN. Study on Liver Dysfunction in Type 2 Diabetic Patients in Bangladesh. Euroasian J Hepato-Gastroenterol 2016;6(1):1-4.

Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos.

Quinalphos (QP) is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin) and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p < 0.05) at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations.