Drug-drug interactions is one of the major determinant in drug development and clinical applications. Individual differences in pharmacokinetics may cause extensive variability in drug efficacy, toxicity and adverse drug reactions, and represent a major concern in drug development. According to world health organization, an estimated 1.2 million patients were diagnosed with HIV/TB coinfection in 2015, and approximately 400,000 coinfected individuals were died in 2016. During treatment of tuberculosis and human immunodeficiency virus (HIV) coinfections, a combination of multiple therapeutic drugs is used, which is potential for interactions between coadministered drugs. Drug metabolizing enzymes and transporters plays vital role in the disposition, pharmacokinetics as well as efficacy and toxicity of many antituberculosis (anti-TB) and antiretroviral (ARVs) drugs. The current understanding of drug-drug interactions involving the first-line antituberculosis and antiretroviral (ARVs) drugs are reviewed and summarized in this article emphasizing the role of drug transporters and metabolic enzymes. It is found that several clinical drug-interactions are caused by the phase I and II metabolic enzymes (cytochrome-P-450s, CYPs, UDP-glucuronosyltransferases, UGTs) and uptake/ efflux transporters, particularly permeability glycoprotein, brest cancer resistance protein, multidrug resistance protein and solute carrier transporters). Overall, this study will be helpful to understand the drug-interactions between the ARV or anti-TB drug regimen or with concomitantly used drugs at a glance. By understanding the unique functions and characteristics of enzymes and transporters, it may use in the management of drug interactions in the treatment of HIV and TB.

Inflammation is associated with the progression of a variety of diseases. Lipopolysaccharides (LPS) tolerance is recognized to reduce proinflammatory responses. Heme oxygenase1 (HO1) and tristetraprolin (TTP) are induced by LPS tolerance and mediate the anti-inflammatory effects. However, it was not clear whether two molecules are linked in LPS tolerance. In this study, we sought to determine whether HO1 associates with TTP to mediate the anti-inflammatory effects of LPS tolerance. LPS treatment significantly increased mRNA and protein level of HO1 and TTP in a time dependant fashion while LPS significantly decreased mRNA and protein level of TNFa in Raw264.7 macrophages. LPS tolerance inhibited TNFa mRNA and protein while HO1 and TTP level was still increased. In HO1 deficient macrophages, LPS tolerance failed to attenuate TNFa mRNA expression but TTP level was still decreased. Our results suggest that HO1 and TTP are functionally linked in mediating anti-inflammatory effects of LPS tolerance. This novel LPS tolerance-HO1-TTP signaling pathway provides new possibilities for the treatment of inflammatory diseases.

MicroRNAs (miRNAs) are a species of noncoding RNA that post-transcriptionally regulates the expression of target mRNAs via degradation or translational repression. Recently, miRNAs in biofluids got extraordinary research priority in the field of noninvasive biomarker development because of their association with pathophysiological events, noninvasive way to obtain, and are markable stability in the extracellular harsh environment. Although several hypotheses have been proposed, the precise mechanisms of cellular release of extracellular miRNAs are not properly understood. In addition, it is often confusing to the researchers, which fraction of biofluid (based on release mechanisms) is suitable for biomarker development research. This review will briefly introduce extracellular miRNAs (EC miRNAs) and their release mechanisms. Furthermore, based on recent evidence, it will also summarize and suggest the appropriate fraction of biofluid to work with for biomarker development.

An investigation was conducted to assess genetic diversity of Bangladesh Agricultural Research Institute (BARI) released 11 varieties of brinjal (BARI begun 1, BARI begun 4-10, BARI hybrid begun 1, 3 and 4) using PCR-based randomly amplified polymorphic DNA (RAPD) markers. A total of 44 distinct DNA amplified bands were observed for five primers (OPB-04, OPB-08, OPD-02, OPP-13 and OPW-08) with an average of 5.6 polymorphic bands per primer. The overall gene diversity was detected 0.216 and level of polymorphism was found 63.64%. The pair wise inter-variety similarity indices ranged from 67.03% to 97.61%. The UPGMA dendrogram segregated 11 genotypes of brinjal into two main clusters. The first major cluster had only one genotype (BARI begun 6) and the second major cluster had rest of ten genotypes. BARI begun 6 vs BARI begun 1 showed the highest Nei’s genetic distance (0.5261) as they are released from different parental origin. On the other hand, BARI begun 9 vs BARI begun 7 varietal pair showed lowest genetic distance (0.0465) as they are released from same parental origin. The experiment reveals genetic diversity and relatedness among 11 brinjal genotypes which may be informative for the future varietal identification and genetic improvement of this vegetable crop.

Histone modification is one of the attractive targets for epigenetic studies. However, current methods to extract chromatin-associated proteins for western blot of histone modification have some weaknesses such as the loss of housekeeping proteins. In this study, we are presenting a simple method to isolate nuclear protein for studying histone modification by immunoblotting with housekeeping proteins. This method provided high protein concentration from minute tissue samples and importantly, it allowed us to detect acetylated histones together with internal control proteins such as ß actin.

Inflammation is associated with the progression of a variety of diseases. Lipopolysaccharides (LPS) tolerance is recognized to reduce proinflammatory responses. Heme oxygenase1 (HO1) and tristetraprolin (TTP) are induced by LPS tolerance and mediate the anti-inflammatory effects. However, it was not clear whether two molecules are linked in LPS tolerance. In this study, we sought to determine whether HO1 associates with TTP to mediate the anti-inflammatory effects of LPS tolerance. LPS treatment significantly increased mRNA and protein level of HO1 and TTP in a time dependant fashion while LPS significantly decreased mRNA and protein level of TNFa in Raw264.7 macrophages. LPS tolerance inhibited TNFa mRNA and protein while HO1 and TTP level was still increased. In HO1 deficient macrophages, LPS tolerance failed to attenuate TNFa mRNA expression but TTP level was still decreased. Our results suggest that HO1 and TTP are functionally linked in mediating anti-inflammatory effects of LPS tolerance. This novel LPS tolerance-HO1-TTP signaling pathway provides new possibilities for the treatment of inflammatory diseases

Drug-drug interactions is one of the major determinant in drug development and clinical applications. Individual differences in pharmacokinetics may cause extensive variability in drug efficacy, toxicity and adverse drug reactions, and represent a major concern in drug development. According to world health organization, an estimated 1.2 million patients were diagnosed with HIV/TB coinfection in 2015, and approximately 400,000 coinfected individuals were died in 2016. During treatment of tuberculosis and human immunodeficiency virus (HIV) coinfections, a combination of multiple therapeutic drugs is used, which is potential for interactions between coadministered drugs. Drug metabolizing enzymes and transporters plays vital role in the disposition, pharmacokinetics as well as efficacy and toxicity of many antituberculosis (anti-TB) and antiretroviral (ARVs) drugs. The current understanding of drug-drug interactions involving the first-line antituberculosis and antiretroviral (ARVs) drugs are reviewed and summarized in this article emphasizing the role of drug transporters and metabolic enzymes. It is found that several clinical drug-interactions are caused by the phase I and II metabolic enzymes (cytochrome-P-450s, CYPs, UDP-glucuronosyltransferases, UGTs) and uptake/ efflux transporters, particularly permeability glycoprotein, brest cancer resistance protein, multidrug resistance protein and solute carrier transporters). Overall, this study will be helpful to understand the drug-interactions between the ARV or anti-TB drug regimen or with concomitantly used drugs at a glance. By understanding the unique functions and characteristics of enzymes and transporters, it may use in the management of drug interactions in the treatment of HIV and TB.

MicroRNAs (miRNAs) are a species of noncoding RNA that post-transcriptionally regulates the expression of target mRNAs via degradation or translational repression. Recently, miRNAs in biofluids got extraordinary research priority in the field of noninvasive biomarker development because of their association with pathophysiological events, noninvasive way to obtain, and are markable stability in the extracellular harsh environment. Although several hypotheses have been proposed, the precise mechanisms of cellular release of extracellular miRNAs are not properly understood. In addition, it is often confusing to the researchers, which fraction of biofluid (based on release mechanisms) is suitable for biomarker development research. This review will briefly introduce extracellular miRNAs (EC miRNAs) and their release mechanisms. Furthermore, based on recent evidence, it will also summarize and suggest the appropriate fraction of biofluid to work with for biomarker development.

An investigation was conducted to assess genetic diversity of Bangladesh Agricultural Research Institute (BARI) released 11 varieties of brinjal (BARI begun 1, BARI begun 4-10, BARI hybrid begun 1, 3 and 4) using PCR-based randomly amplified polymorphic DNA (RAPD) markers. A total of 44 distinct DNA amplified bands were observed for five primers (OPB-04, OPB-08, OPD-02, OPP-13 and OPW-08) with an average of 5.6 polymorphic bands per primer. The overall gene diversity was detected 0.216 and level of polymorphism was found 63.64%. The pair wise inter-variety similarity indices ranged from 67.03% to 97.61%. The UPGMA dendrogram segregated 11 genotypes of brinjal into two main clusters. The first major cluster had only one genotype (BARI begun 6) and the second major cluster had rest of ten genotypes. BARI begun 6 vs BARI begun 1 showed the highest Nei’s genetic distance (0.5261) as they are released from different parental origin. On the other hand, BARI begun 9 vs BARI begun 7 varietal pair showed lowest genetic distance (0.0465) as they are released from same parental origin. The experiment reveals genetic diversity and relatedness among 11 brinjal genotypes which may be informative for the future varietal identification and genetic improvement of this vegetable crop.

Histone modification is one of the attractive targets for epigenetic studies. However, current methods to extract chromatin-associated proteins for western blot of histone modification have some weaknesses such as the loss of housekeeping proteins. In this study, we are presenting a simple method to isolate nuclear protein for studying histone modification by immunoblotting with housekeeping proteins. This method provided high protein concentration from minute tissue samples and importantly, it allowed us to detect acetylated histones together with internal control proteins such as ß actin.