The profound impact of mitochondrion in cellular metabolism has been well documented. Since type 2 diabetes (T2D) is a metabolic disorder, mitochondrial dysfunction is intricately linked with the disease pathogenesis. Mitochondrial DNA (mtDNA) variants are involved with functional dysfunction of mitochondrion and play a pivotal role in the susceptibility to T2D. In this study, we opted to find the association of mtDNA variants within the D-loop hypervariable region I (HVI), haplogroups and mtDNA copy number with T2D in Bangladeshi population. A total of 300 unrelated Bangladeshi individuals (150 healthy and 150 patients with T2D) were recruited in the present study, their HVI regions were amplified and sequenced using Sanger chemistry. Haplogrep2 and Phylotree17 tools were employed to determine the haplogroups. MtDNA copy number was measured using primers of mitochondrial tRNA Leu (UUR) gene and nuclear β2-microglobulin gene. Variants G16048A (OR:0.12, p = 0.04) and G16129A (OR: 0.42, p = 0.007) were found to confer protective role against T2D according to logistic regression analysis. However along with G16129A, two new variants C16294T and T16325C demonstrated protective role against T2D when age and gender were adjusted. Haplogroups A and H showed significant association with the risk of T2D after adjustments out of total 19 major haplogroups identified. The mtDNA copy numbers were stratified into 4 groups according to the quartiles (groups with lower, medium, upper and higher mtDNA copy numbers were respectively designated as LCN, MCN, UCN and HCN). Patients with T2D had significantly lower mtDNA copy number compared to their healthy counterparts in HCN group. Moreover, six mtDNA variants were significantly associated with mtDNA copy number in the participants. Thus, our study confers that certain haplogroups and novel variants of mtDNA are significantly associated with T2D while decreased mtDNA copy number (though not significant) has been observed in patients with T2D. However, largescale studies are warranted to establish association of novel variants and haplogroup with type 2 diabetes.

Myocardial ischemic injury and its resolution are the key determinants of morbidity or mortality in heart failure. The cause and duration of ischemia in patients vary. Numerous experimental models and methods have been developed to define genetic, metabolic, molecular, cellular, and pathophysiological mechanisms, in addition to defining structural and functional deterioration of cardiovascular performance. The rapid rise of big data, such as single-cell analysis techniques with bioinformatics, machine learning and neural networking, bring a new level of sophistication to our understanding of myocardial ischemia. This mini-review explores the multi-faceted nature of ischemic injury in the myocardium. We highlight recent state-of-the-art findings, and strategies to show new directions of high impact approach to understanding myocardial tissue remodeling. This next age of heart and circulatory physiology research will be more comprehensive and collaborative to uncover the origin, progression and manifestation of heart failure, while strengthening novel treatment strategies.

No abstract

The current study elucidated an association between gene variants and thrombocytopenia through the investigation of the exonic polymorphic landscape of hematopoietic transcription factor—GATA1 gene in dengue patients. A total of 115 unrelated dengue patients with dengue fever (DF) (N = 91) and dengue hemorrhagic fever (DHF) (N = 24) were included in the study. All dengue patients were confirmed through detection of NS1 antigen, IgM, and IgG antibodies against the dengue virus. Polymerase chain reaction using specific primers amplified the exonic regions of GATA1 while Sanger sequencing and chromatogram analyses facilitated the identification of variants. Variants G>A (at chX: 48792009) and C>A (at chX: 4879118) had higher frequency out of 13 variants identified (3 annotated and 10 newly recognized). Patients carrying either nonsynonymous or synonymous variants had significantly lower mean values of platelets compared to those harboring the reference nucleotides (NC_000023.11). Further analyses revealed that the change in amino acid residue leads to the altered three-dimensional structure followed by interaction with neighboring residues. Increased stability of the protein due to substitution of serine by asparagine (S129N at chX: 48792009) may cause increased rigidity followed by reduced structural flexibility which may ultimately disturb the dimerization (an important prerequisite for GATA1 to perform its biological activity) process of the GATA1 protein. This, in turn, may affect the function of GATA1 followed by impaired production of mature platelets which may be reflected by the lower platelet counts in individuals with such variation. In summary, we have identified new variants within the GATA1 gene which were found to be clinically relevant to the outcome of dengue patients and thus, have the potential as candidate biomarkers for the determination of severity and prognosis of thrombocytopenia caused by dengue virus. However, further validation of this study in a large number of dengue patients is warranted. Trial Registration: number SLCTR/2019/037.

No abstract