Background: Complementary medicines, including homeopathy, are used by many patients with cancer,... more Background: Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. However, the molecular mechanisms underneath the anti-cancer effect, if any, of these medicines have still remained unexplored. To this end we attempted to evaluate the efficacy of calcarea carbonica, a homeopathic medicine, as an anti-cancer agent and to delineate the detail molecular mechanism(s) underlying calcerea carbonica-induced tumor regression. Methods: To investigate and delineate the underlying mechanisms of calcarea carbonica-induced tumor regression, Trypan blue dye-exclusion test, flow cytometric, Western blot and reverse transcriptase-PCR techniques were employed. Further, siRNA transfections and inhibitor studies were used to validate the involvement of p53 pathway in calcarea carbonica-induced apoptosis in cancer cells. Results: Interestingly, although calcarea carbonica administration to Ehrlich's ascites carcinoma (EAC)-and Sarcoma-180 (S-180)-bearing Swiss albino mice resulted in 30-35% tumor cell apoptosis, it failed to induce any significant cell death in ex vivo conditions. These results prompted us to examine whether calcarea carbonica employs the immuno-modulatory circuit in asserting its anti-tumor effects. Calcarea carbonica prevented tumor-induced loss of effector T cell repertoire, reversed type-2 cytokine bias and attenuated tumor-induced inhibition of T cell proliferation in tumor-bearing host. To confirm the role of immune system in calcarea carbonica-induced cancer cell death, a battery of cancer cells were co-cultured with calcarea carbonica-primed T cells. Our results indicated a "two-step" mechanism of the induction of apoptosis in tumor cells by calcarea carbonica i.e., (1) activation of the immune system of the host; and (2) induction of cancer cell apoptosis via immuno-modulatory circuit in p53dependent manner by down-regulating Bcl-2:Bax ratio. Bax up-regulation resulted in mitochondrial transmembrane potential loss and cytochrome c release followed by activation of caspase cascade. Knocking out of p53 by RNAinterference inhibited calcarea carbonica-induced apoptosis thereby confirming the contribution of p53. Conclusion: These observations delineate the significance of immuno-modulatory circuit during calcarea carbonicamediated tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea carbonica into immunotherapeutic strategies for effective tumor regression.
Much of our current understanding of how small-molecule ligands interact with proteins stems from... more Much of our current understanding of how small-molecule ligands interact with proteins stems from X-ray crystal structures determined at cryogenic (cryo) temperature. For proteins alone, room-temperature (RT) crystallography can reveal previously hidden, biologically relevant alternate conformations. However, less is understood about how RT crystallography may impact the conformational landscapes of protein-ligand complexes. Previously we showed that small-molecule fragments cluster in putative allosteric sites using a cryo crystallographic screen of the therapeutic target PTP1B (Keedy*, Hill*, 2018). Here we have performed two RT crystallographic screens of PTP1B using many of the same fragments, representing the largest RT crystallographic screens of a diverse library of ligands to date, and enabling a direct interrogation of the effect of data collection temperature on protein-ligand interactions. We show that at RT, fewer ligands bind, and often more weakly -- but with a variety...
Obesity related conditions including atherosclerosis and type 2 diabetes mellitus (T2DM) have a p... more Obesity related conditions including atherosclerosis and type 2 diabetes mellitus (T2DM) have a profound effect on cardiovascular health and morbidity. Recent reports by Akbari et. al. indicate that truncated loss of function variants of the orphan G-protein coupled receptor, GPR75, are associated with 5.3 kg lower bodyweight and 54% lower odds of obesity in heterozygous individuals (Science, 2021) . Based on these findings, we hypothesized that whole body deletion of Gpr75 protects against diet-induced obesity (DIO) and the resulting insulin resistance. Wild-type and Gpr75 null mice were subjected to 14 weeks of regular chow or high-fat diet (HFD) feeding. Body weight, intraperitoneal glucose and insulin tolerance tests, and pro-inflammatory cytokine gene expressions were measured initially and at week 14. There were no significant differences in body weight, glucose homeostasis, and tumor necrosis factor alpha (TNF-α) expression between wild-type (WT) and Gpr75 -/- (KO) mice at ba...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2020
20-Hydroxyeicosatetraenoic acid (20-HETE) has been linked to blood pressure (BP) regulation via a... more 20-Hydroxyeicosatetraenoic acid (20-HETE) has been linked to blood pressure (BP) regulation via actions on the renal microvasculature and tubules. We assessed the tubular 20-HETE contribution to hypertension by generating transgenic mice overexpressing the CYP4A12-20-HETE synthase (PT-4a12 mice) under the control of the proximal tubule (PT)-specific promoter phosphoenolpyruvate carboxykinase (PEPCK). 20-HETE levels in the kidney cortex of male (967 ± 210 vs. 249 ± 69 pg/mg protein) but not female (121 ± 15 vs. 92 ± 11 pg/mg protein) PT-4a12 mice showed a 2.5-fold increase compared with wild type (WT). Renal cortical Cyp4a12 mRNA and CYP4A12 protein in male but not female PT-4a12 mice increased by two- to threefold compared with WT. Male PT-4a12 mice displayed elevated BP (142 ± 1 vs. 111 ± 4 mmHg, P < 0.0001), whereas BP in female PT-4a12 mice was not significantly different from WT (118 ± 2 vs. 117 ± 2 mmHg; P = 0.98). In male PT-4a12 mice, BP decreased when mice were transition...
Calcarea carbonica induces apoptosis in cancer anner via an potential loss and cytochrome c relea... more Calcarea carbonica induces apoptosis in cancer anner via an potential loss and cytochrome c release followed by activation of caspase cascade. Knocking out of p53 by RNA-Saha et al. BMC Complementary and Alternative Medicine 2013, 13:230
Electricity generation using solar thermal power systems can be made more efficient and both tech... more Electricity generation using solar thermal power systems can be made more efficient and both technically and economically feasible in countries receiving moderate solar radiation like Bangladesh through thorough optimization of different parts of the power plant. In this paper a theoretical and mathematical framework for optimization of a 150 MW solar tower thermal power plant in Bangladesh which uses molten salt as HTF has been developed by applying different methods of selecting crucial design aspects, such as design point DNI, solar multiple, design point temperature etc. after selecting the most appropriate location based on GHI and DNI data. The effect of these design aspects on the overall design of the power plant including the number of heliostats, solar field land area, tower height, receiver dimensions etc. have also been studied and finally the performance analysis of the power plant has been conducted. Analysis of performance reveals that the optimized power plant would ...
2021 12th International Conference on Computing Communication and Networking Technologies (ICCCNT), 2021
In this modern era, several new programming languages are introduced among the programmers and ar... more In this modern era, several new programming languages are introduced among the programmers and are the benediction for them but there are some challenging issues. The major problem of a programmer to memorize the syntaxes of different programming languages at the same time. It is very common among the programmers to mix up the syntaxes of different programming languages during coding. Moreover, the people who are suffering with Parkinson's disease cannot do programming because of their shaky hands. In additional, hand typing programming takes enough time to perform the coding. This study discusses how to reduce typing problems by hands, syntax memorization problems and time consuming problems during programming. However, the proposed system named VCL (Voice Command Language) is a very easy and time saving software. This software is capable of coding on multiple programming languages (such as Python, Java and C) by using same voice command against the syntax for all languages. Voice command is recognized by the Google Speech API and then software generate the code against the command. This software will help the programmers to focus more on logics rather than memorizing the syntaxes. The study will also help the programmers to speed up their programming performance and will create a new window for the hand injured people.
Proceedings of International Exchange and Innovation Conference on Engineering & Sciences (IEICES), 2020
Solar energy is the most copious source of energy worldwide and is regarded as a major substitute... more Solar energy is the most copious source of energy worldwide and is regarded as a major substitute of fossil fuels in the field of electricity generation. Electricity can be generated from Solar energy by employing two different methods: Photovoltaic (PV) Conversion and the thermodynamic cycles powered by CSP technologies. Lower lifetime and efficiency of Photovoltaics have created an inclination towards the use and development of CSP technologies. In this study, a 100MW solar tower based thermal power plant is designed, optimized and simulated using System Advisor Model (SAM) to achieve a technically feasible project keeping the climate of Bangladesh in mind. A location (21°35′0″N 92°01′0″E) beside the river Bakkhali in Cox's Bazar receiving more or less constant DNI throughout the year (Annual DNI 1905Kwh/m²) is selected for the study. The simulation results show that the hypothetical power plant can supply 374.55 GWh electricity to the national grid annually while operating at 42.7% capacity factor with a gross to net conversion efficiency of 88.1%. The optimized design and performance of the power plant encourage further innovation and development of solar tower based thermal power plants in Bangladesh.
Laboratory experiment was conducted to study the biochemical and quality parameters of tea i.e. P... more Laboratory experiment was conducted to study the biochemical and quality parameters of tea i.e. Polyphenol, Theaflavin (TF), Thearubigin (TR), Caffeine, Lipid, Total ash, Chlorophyll, Moisture content etc. under different variables designed for age, topography, and processing system imposed on an established tea orchard. Results revealed that plant age and topography do not have any significant effect on most of the studied parameters. In case of plant age, tannin is found to be significantly higher in mature tea plant (39.35 ppm) whereas young plant showed significantly lower total sugar content (28.98 ppm). In case of land elevation, significantly higher tannin (37.41 ppm) and lower carotenoid content (0.74 mg/g) were evident in plants from kunchi topography where flat topography showed significantly higher total sugar (26.62 ppm) in leaves. The handmade tea flavoured with significantly higher amount of polyphenol (58.57 ppm) and caffein (43.30 ppm) but industry made tea showed si...
How genes affect human obesity Obesity is linked to many human diseases, including diabetes, canc... more How genes affect human obesity Obesity is linked to many human diseases, including diabetes, cancer, and heart disease. There is thus great interest in understanding how genes predispose individuals to, or protect individuals from, obesity. Akbari et al. sequenced more than 600,000 exomes from the United Kingdom, the United States, and Mexico and identified 16 rare coding variants (see the Perspective by Yeo and O'Rahilly). Some of the alleles associated with body mass index (BMI) were brain-expressed G protein–coupled receptors. One variant allele was found in Mexican populations at low frequency and was associated with lower BMI. Deletion of this gene in mice resulted in a resistance to weight gain, suggesting that this gene provides an avenue of study for the prevention or treatment of obesity. Science , abf8683, this issue p. eabf8683 ; see also abh3556, p. 30
20-HETE, a metabolite of arachidonic acid produced by Cytochrome P450 (CYP) 4A/4F, has been impli... more 20-HETE, a metabolite of arachidonic acid produced by Cytochrome P450 (CYP) 4A/4F, has been implicated in the development of obesity-associated complications such as diabetes and insulin resistance. In this study, we examined whether the acute elevation of 20-HETE levels contributes to the development of diet-driven hyperglycemia and insulin resistance. We employed a conditional transgenic mouse model to overexpress Cyp4a12 (Cyp4a12tg), a murine 20-HETE synthase, together with high fat diet (HFD) feeding. Mice in which Cyp4a12 was induced by doxycycline (DOX) at the onset of HFD feeding gained weight at a greater rate and extent than corresponding DOX-untreated Cyp4a12 mice. Cyp4a12tg mice fed HFD+DOX displayed hyperglycemia and impaired glucose metabolism while corresponding HFD-fed Cyp4a12tg mice (no DOX) did not. Importantly, administration of a 20-HETE antagonist, 20-SOLA, to Cyp4a12tg mice fed HFD+DOX significantly attenuated weight gain and prevented the development of hyperglycemia and impaired glucose metabolism. Levels of insulin receptor (IR) phosphorylation at Tyrosine 972 and insulin receptor substrate-1 (IRS1) phosphorylation at serine 307 were markedly decreased and increased, respectively, in liver, skeletal muscle and adipose tissues from Cyp4a12tg mice fed HFD+DOX; 20-SOLA prevented the IR and IRS1 inactivation, suggesting that 20-HETE interferes with insulin signaling. Additional studies in 3T3-1 differentiated adipocytes confirmed that 20-HETE impairs insulin signaling and that its effect may require activation of its receptor GPR75. Taken together, these results provide strong evidence that 20-HETE interferes with insulin function and contributed to diet-driven insulin resistance.
The purpose of this study is to understand how one of the most non-renewable countries is acting ... more The purpose of this study is to understand how one of the most non-renewable countries is acting concerning the global challenge of energy supply vs. resources for energy generation. Saudi Arabia is registering the highest energy consumption per capita in the world with its fastest population growth and the rapid pace of industrialization. Its electricity consumption is expected to be more than doubled by 2025, and the carbon emission is supposed to be on the rise. In that backdrop, Saudi Arabia has taken many steps to shift its dependency from oil to solar, wind and nuclear sources of energy, and plans to secure half of the country's electricity needs from the alternative sources of energy in coming 20 years. The government has announced an ambitious plan to install 41 Giga Watt of solar capacity and invest $108.9 billion by 2032. This exploratory study reviews the steps undertaken in this regard to promote the solar energy initiative as envisaged by the government. This paper discusses the issues and challenges in shifting from oil to solar energy in Saudi Arabia. It documents and discusses the drivers that push Saudi Arabia to adopt solar as an alternative source of energy that can be used to reduce oil dependency and to improve environmental sustainability. A multi-pronged approach involving all stakeholders is the key to success in making the solar project sustainable in Saudi Arabia.
STAT3 transcription factor plays central role for survival, metastasis and immune evasion of many... more STAT3 transcription factor plays central role for survival, metastasis and immune evasion of many solid and blood tumors. In acute myeloid leukemia (AML), STAT3 is a critical node in signaling from numerous tyrosine kinases. Thus, it is an attractive but also elusive pharmacological target. We have recently shown that linking siRNA molecules to Toll-like receptor 9 (TLR9) ligands, CpG oligonucleotides, allows for cell-specific siRNA delivery in vivo. CpG-STAT3 siRNA conjugates induce RNAi in both mouse and human immune cells resulting in potent immunostimulatory effects. TLR9 is also commonly expressed in blood cancers, such as AML. We assessed whether targeting STAT3 in both leukemic and in tumor-associated immune cells using CpG-STAT3 siRNA can augment antitumor effects. We used orthotopic models of mouse Cbfb-MYH11 leukemia on 129Sv and C57BL/6 genetic backgrounds, which closely mimic human inv(16) AML. Our results demonstrated that intravenous injections of CpG-STAT3 siRNA (5 mg...
This paper presents a novel method of multi-drug scheduling using multi-objective genetic algorit... more This paper presents a novel method of multi-drug scheduling using multi-objective genetic algorithm (MOGA) that can find suitable/optimum dosages by trading-off between cell killing and toxic side-effects of chemotherapy treatment. A close-loop control method, namely Integral-Proportional-Derivative (I-PD) is designed to control dosages of drugs to be infused to the patient's body and MOGA is used to find suitable parameters of the controller. A cell compartments model is developed and used to describe the effects of the drugs on different type of cells, plasma drug concentration and toxic side-effects. Results show that specific drug schedule obtained through the proposed method can reduce the tumour size nearly 100% with relatively lower toxic side-effects.
Background: Complementary medicines, including homeopathy, are used by many patients with cancer,... more Background: Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. However, the molecular mechanisms underneath the anti-cancer effect, if any, of these medicines have still remained unexplored. To this end we attempted to evaluate the efficacy of calcarea carbonica, a homeopathic medicine, as an anti-cancer agent and to delineate the detail molecular mechanism(s) underlying calcerea carbonica-induced tumor regression. Methods: To investigate and delineate the underlying mechanisms of calcarea carbonica-induced tumor regression, Trypan blue dye-exclusion test, flow cytometric, Western blot and reverse transcriptase-PCR techniques were employed. Further, siRNA transfections and inhibitor studies were used to validate the involvement of p53 pathway in calcarea carbonica-induced apoptosis in cancer cells. Results: Interestingly, although calcarea carbonica administration to Ehrlich's ascites carcinoma (EAC)-and Sarcoma-180 (S-180)-bearing Swiss albino mice resulted in 30-35% tumor cell apoptosis, it failed to induce any significant cell death in ex vivo conditions. These results prompted us to examine whether calcarea carbonica employs the immuno-modulatory circuit in asserting its anti-tumor effects. Calcarea carbonica prevented tumor-induced loss of effector T cell repertoire, reversed type-2 cytokine bias and attenuated tumor-induced inhibition of T cell proliferation in tumor-bearing host. To confirm the role of immune system in calcarea carbonica-induced cancer cell death, a battery of cancer cells were co-cultured with calcarea carbonica-primed T cells. Our results indicated a "two-step" mechanism of the induction of apoptosis in tumor cells by calcarea carbonica i.e., (1) activation of the immune system of the host; and (2) induction of cancer cell apoptosis via immuno-modulatory circuit in p53dependent manner by down-regulating Bcl-2:Bax ratio. Bax up-regulation resulted in mitochondrial transmembrane potential loss and cytochrome c release followed by activation of caspase cascade. Knocking out of p53 by RNAinterference inhibited calcarea carbonica-induced apoptosis thereby confirming the contribution of p53. Conclusion: These observations delineate the significance of immuno-modulatory circuit during calcarea carbonicamediated tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea carbonica into immunotherapeutic strategies for effective tumor regression.
Much of our current understanding of how small-molecule ligands interact with proteins stems from... more Much of our current understanding of how small-molecule ligands interact with proteins stems from X-ray crystal structures determined at cryogenic (cryo) temperature. For proteins alone, room-temperature (RT) crystallography can reveal previously hidden, biologically relevant alternate conformations. However, less is understood about how RT crystallography may impact the conformational landscapes of protein-ligand complexes. Previously we showed that small-molecule fragments cluster in putative allosteric sites using a cryo crystallographic screen of the therapeutic target PTP1B (Keedy*, Hill*, 2018). Here we have performed two RT crystallographic screens of PTP1B using many of the same fragments, representing the largest RT crystallographic screens of a diverse library of ligands to date, and enabling a direct interrogation of the effect of data collection temperature on protein-ligand interactions. We show that at RT, fewer ligands bind, and often more weakly -- but with a variety...
Obesity related conditions including atherosclerosis and type 2 diabetes mellitus (T2DM) have a p... more Obesity related conditions including atherosclerosis and type 2 diabetes mellitus (T2DM) have a profound effect on cardiovascular health and morbidity. Recent reports by Akbari et. al. indicate that truncated loss of function variants of the orphan G-protein coupled receptor, GPR75, are associated with 5.3 kg lower bodyweight and 54% lower odds of obesity in heterozygous individuals (Science, 2021) . Based on these findings, we hypothesized that whole body deletion of Gpr75 protects against diet-induced obesity (DIO) and the resulting insulin resistance. Wild-type and Gpr75 null mice were subjected to 14 weeks of regular chow or high-fat diet (HFD) feeding. Body weight, intraperitoneal glucose and insulin tolerance tests, and pro-inflammatory cytokine gene expressions were measured initially and at week 14. There were no significant differences in body weight, glucose homeostasis, and tumor necrosis factor alpha (TNF-α) expression between wild-type (WT) and Gpr75 -/- (KO) mice at ba...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2020
20-Hydroxyeicosatetraenoic acid (20-HETE) has been linked to blood pressure (BP) regulation via a... more 20-Hydroxyeicosatetraenoic acid (20-HETE) has been linked to blood pressure (BP) regulation via actions on the renal microvasculature and tubules. We assessed the tubular 20-HETE contribution to hypertension by generating transgenic mice overexpressing the CYP4A12-20-HETE synthase (PT-4a12 mice) under the control of the proximal tubule (PT)-specific promoter phosphoenolpyruvate carboxykinase (PEPCK). 20-HETE levels in the kidney cortex of male (967 ± 210 vs. 249 ± 69 pg/mg protein) but not female (121 ± 15 vs. 92 ± 11 pg/mg protein) PT-4a12 mice showed a 2.5-fold increase compared with wild type (WT). Renal cortical Cyp4a12 mRNA and CYP4A12 protein in male but not female PT-4a12 mice increased by two- to threefold compared with WT. Male PT-4a12 mice displayed elevated BP (142 ± 1 vs. 111 ± 4 mmHg, P < 0.0001), whereas BP in female PT-4a12 mice was not significantly different from WT (118 ± 2 vs. 117 ± 2 mmHg; P = 0.98). In male PT-4a12 mice, BP decreased when mice were transition...
Calcarea carbonica induces apoptosis in cancer anner via an potential loss and cytochrome c relea... more Calcarea carbonica induces apoptosis in cancer anner via an potential loss and cytochrome c release followed by activation of caspase cascade. Knocking out of p53 by RNA-Saha et al. BMC Complementary and Alternative Medicine 2013, 13:230
Electricity generation using solar thermal power systems can be made more efficient and both tech... more Electricity generation using solar thermal power systems can be made more efficient and both technically and economically feasible in countries receiving moderate solar radiation like Bangladesh through thorough optimization of different parts of the power plant. In this paper a theoretical and mathematical framework for optimization of a 150 MW solar tower thermal power plant in Bangladesh which uses molten salt as HTF has been developed by applying different methods of selecting crucial design aspects, such as design point DNI, solar multiple, design point temperature etc. after selecting the most appropriate location based on GHI and DNI data. The effect of these design aspects on the overall design of the power plant including the number of heliostats, solar field land area, tower height, receiver dimensions etc. have also been studied and finally the performance analysis of the power plant has been conducted. Analysis of performance reveals that the optimized power plant would ...
2021 12th International Conference on Computing Communication and Networking Technologies (ICCCNT), 2021
In this modern era, several new programming languages are introduced among the programmers and ar... more In this modern era, several new programming languages are introduced among the programmers and are the benediction for them but there are some challenging issues. The major problem of a programmer to memorize the syntaxes of different programming languages at the same time. It is very common among the programmers to mix up the syntaxes of different programming languages during coding. Moreover, the people who are suffering with Parkinson's disease cannot do programming because of their shaky hands. In additional, hand typing programming takes enough time to perform the coding. This study discusses how to reduce typing problems by hands, syntax memorization problems and time consuming problems during programming. However, the proposed system named VCL (Voice Command Language) is a very easy and time saving software. This software is capable of coding on multiple programming languages (such as Python, Java and C) by using same voice command against the syntax for all languages. Voice command is recognized by the Google Speech API and then software generate the code against the command. This software will help the programmers to focus more on logics rather than memorizing the syntaxes. The study will also help the programmers to speed up their programming performance and will create a new window for the hand injured people.
Proceedings of International Exchange and Innovation Conference on Engineering & Sciences (IEICES), 2020
Solar energy is the most copious source of energy worldwide and is regarded as a major substitute... more Solar energy is the most copious source of energy worldwide and is regarded as a major substitute of fossil fuels in the field of electricity generation. Electricity can be generated from Solar energy by employing two different methods: Photovoltaic (PV) Conversion and the thermodynamic cycles powered by CSP technologies. Lower lifetime and efficiency of Photovoltaics have created an inclination towards the use and development of CSP technologies. In this study, a 100MW solar tower based thermal power plant is designed, optimized and simulated using System Advisor Model (SAM) to achieve a technically feasible project keeping the climate of Bangladesh in mind. A location (21°35′0″N 92°01′0″E) beside the river Bakkhali in Cox's Bazar receiving more or less constant DNI throughout the year (Annual DNI 1905Kwh/m²) is selected for the study. The simulation results show that the hypothetical power plant can supply 374.55 GWh electricity to the national grid annually while operating at 42.7% capacity factor with a gross to net conversion efficiency of 88.1%. The optimized design and performance of the power plant encourage further innovation and development of solar tower based thermal power plants in Bangladesh.
Laboratory experiment was conducted to study the biochemical and quality parameters of tea i.e. P... more Laboratory experiment was conducted to study the biochemical and quality parameters of tea i.e. Polyphenol, Theaflavin (TF), Thearubigin (TR), Caffeine, Lipid, Total ash, Chlorophyll, Moisture content etc. under different variables designed for age, topography, and processing system imposed on an established tea orchard. Results revealed that plant age and topography do not have any significant effect on most of the studied parameters. In case of plant age, tannin is found to be significantly higher in mature tea plant (39.35 ppm) whereas young plant showed significantly lower total sugar content (28.98 ppm). In case of land elevation, significantly higher tannin (37.41 ppm) and lower carotenoid content (0.74 mg/g) were evident in plants from kunchi topography where flat topography showed significantly higher total sugar (26.62 ppm) in leaves. The handmade tea flavoured with significantly higher amount of polyphenol (58.57 ppm) and caffein (43.30 ppm) but industry made tea showed si...
How genes affect human obesity Obesity is linked to many human diseases, including diabetes, canc... more How genes affect human obesity Obesity is linked to many human diseases, including diabetes, cancer, and heart disease. There is thus great interest in understanding how genes predispose individuals to, or protect individuals from, obesity. Akbari et al. sequenced more than 600,000 exomes from the United Kingdom, the United States, and Mexico and identified 16 rare coding variants (see the Perspective by Yeo and O'Rahilly). Some of the alleles associated with body mass index (BMI) were brain-expressed G protein–coupled receptors. One variant allele was found in Mexican populations at low frequency and was associated with lower BMI. Deletion of this gene in mice resulted in a resistance to weight gain, suggesting that this gene provides an avenue of study for the prevention or treatment of obesity. Science , abf8683, this issue p. eabf8683 ; see also abh3556, p. 30
20-HETE, a metabolite of arachidonic acid produced by Cytochrome P450 (CYP) 4A/4F, has been impli... more 20-HETE, a metabolite of arachidonic acid produced by Cytochrome P450 (CYP) 4A/4F, has been implicated in the development of obesity-associated complications such as diabetes and insulin resistance. In this study, we examined whether the acute elevation of 20-HETE levels contributes to the development of diet-driven hyperglycemia and insulin resistance. We employed a conditional transgenic mouse model to overexpress Cyp4a12 (Cyp4a12tg), a murine 20-HETE synthase, together with high fat diet (HFD) feeding. Mice in which Cyp4a12 was induced by doxycycline (DOX) at the onset of HFD feeding gained weight at a greater rate and extent than corresponding DOX-untreated Cyp4a12 mice. Cyp4a12tg mice fed HFD+DOX displayed hyperglycemia and impaired glucose metabolism while corresponding HFD-fed Cyp4a12tg mice (no DOX) did not. Importantly, administration of a 20-HETE antagonist, 20-SOLA, to Cyp4a12tg mice fed HFD+DOX significantly attenuated weight gain and prevented the development of hyperglycemia and impaired glucose metabolism. Levels of insulin receptor (IR) phosphorylation at Tyrosine 972 and insulin receptor substrate-1 (IRS1) phosphorylation at serine 307 were markedly decreased and increased, respectively, in liver, skeletal muscle and adipose tissues from Cyp4a12tg mice fed HFD+DOX; 20-SOLA prevented the IR and IRS1 inactivation, suggesting that 20-HETE interferes with insulin signaling. Additional studies in 3T3-1 differentiated adipocytes confirmed that 20-HETE impairs insulin signaling and that its effect may require activation of its receptor GPR75. Taken together, these results provide strong evidence that 20-HETE interferes with insulin function and contributed to diet-driven insulin resistance.
The purpose of this study is to understand how one of the most non-renewable countries is acting ... more The purpose of this study is to understand how one of the most non-renewable countries is acting concerning the global challenge of energy supply vs. resources for energy generation. Saudi Arabia is registering the highest energy consumption per capita in the world with its fastest population growth and the rapid pace of industrialization. Its electricity consumption is expected to be more than doubled by 2025, and the carbon emission is supposed to be on the rise. In that backdrop, Saudi Arabia has taken many steps to shift its dependency from oil to solar, wind and nuclear sources of energy, and plans to secure half of the country's electricity needs from the alternative sources of energy in coming 20 years. The government has announced an ambitious plan to install 41 Giga Watt of solar capacity and invest $108.9 billion by 2032. This exploratory study reviews the steps undertaken in this regard to promote the solar energy initiative as envisaged by the government. This paper discusses the issues and challenges in shifting from oil to solar energy in Saudi Arabia. It documents and discusses the drivers that push Saudi Arabia to adopt solar as an alternative source of energy that can be used to reduce oil dependency and to improve environmental sustainability. A multi-pronged approach involving all stakeholders is the key to success in making the solar project sustainable in Saudi Arabia.
STAT3 transcription factor plays central role for survival, metastasis and immune evasion of many... more STAT3 transcription factor plays central role for survival, metastasis and immune evasion of many solid and blood tumors. In acute myeloid leukemia (AML), STAT3 is a critical node in signaling from numerous tyrosine kinases. Thus, it is an attractive but also elusive pharmacological target. We have recently shown that linking siRNA molecules to Toll-like receptor 9 (TLR9) ligands, CpG oligonucleotides, allows for cell-specific siRNA delivery in vivo. CpG-STAT3 siRNA conjugates induce RNAi in both mouse and human immune cells resulting in potent immunostimulatory effects. TLR9 is also commonly expressed in blood cancers, such as AML. We assessed whether targeting STAT3 in both leukemic and in tumor-associated immune cells using CpG-STAT3 siRNA can augment antitumor effects. We used orthotopic models of mouse Cbfb-MYH11 leukemia on 129Sv and C57BL/6 genetic backgrounds, which closely mimic human inv(16) AML. Our results demonstrated that intravenous injections of CpG-STAT3 siRNA (5 mg...
This paper presents a novel method of multi-drug scheduling using multi-objective genetic algorit... more This paper presents a novel method of multi-drug scheduling using multi-objective genetic algorithm (MOGA) that can find suitable/optimum dosages by trading-off between cell killing and toxic side-effects of chemotherapy treatment. A close-loop control method, namely Integral-Proportional-Derivative (I-PD) is designed to control dosages of drugs to be infused to the patient's body and MOGA is used to find suitable parameters of the controller. A cell compartments model is developed and used to describe the effects of the drugs on different type of cells, plasma drug concentration and toxic side-effects. Results show that specific drug schedule obtained through the proposed method can reduce the tumour size nearly 100% with relatively lower toxic side-effects.
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Papers by Sakib Hossain