Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanisms by which coronavirus disease 2019 causes thrombocytopenia to better understand this disease and provide more clinical treatment options.

The distinction between mild pathogenic mtDNA mutations and population polymorphisms can be ambiguous because both are homoplasmic, alter conserved functions, and correlate with disease. One possible explanation for this ambiguity is that the same variant may have different consequences in different contexts. The NADH dehydrogenase subunit 1 (ND1) nucleotide 3394 T > C (Y30H) variant is such a case. This variant has been associated with Leber hereditary optic neuropathy and it reduces complex I activity and cellular respiration between 7% and 28% on the Asian B4c and F1 haplogroup backgrounds. However, complex I activity between B4c and F1 mtDNAs, which harbor the common 3394T allele, can also differ by 30%. In Asia, the 3394C variant is most commonly associated with the M9 haplogroup, which is rare at low elevations but increases in frequency with elevation to an average of 25% of the Tibetan mtDNAs (odds ratio = 23.7). In high-altitude Tibetan and Indian populations, the 3394C variant occurs on five different macrohaplogroup M haplogroup backgrounds and is enriched on the M9 background in Tibet and the C4a4 background on the Indian Deccan Plateau (odds ratio = 21.9). When present on the M9 background, the 3394C variant is associated with a complex I activity that is equal to or higher than that of the 3394T variant on the B4c and F1 backgrounds. Hence, the 3394C variant can either be deleterious or beneficial depending on its haplogroup and environmental context. Thus, this mtDNA variant fulfills the criteria for a common variant that predisposes to a "complex" disease.

The endoplasmic reticulum (ER) is an organelle entrusted with lipid synthesis, calcium homeostasis, protein folding, and maturation. Perturbation of ER-associated functions results in an evolutionarily conserved cell stress response, the unfolded protein response (UPR) that is also called ER stress. ER stress is aimed initially at compensating for damage but can eventually trigger cell death if ER stress is excessive or prolonged. Now the ER stress has been associated with numerous diseases. For instance, our recent studies have demonstrated the important role of ER stress in diabetes-induced cardiac cell death. It is known that apoptosis has been considered to play a critical role in diabetic cardiomyopathy. Therefore, this paper will summarize the information from the literature and our own studies to focus on the pathological role of ER stress in the development of diabetic cardiomyopathy. Improved understanding of the molecular mechanisms underlying UPR activation and ER-initiated apoptosis in diabetic cardiomyopathy will provide us with new targets for drug discovery and therapeutic intervention.

Acute lung injury (ALI) is a devastating disease, which is characterized by diffuse endothelium, epithelial damage, and increased pulmonary capillary permeability. Recent data have suggested that the circulating endothelial progenitor cells (EPCs) play an important role in endothelial repair after vascular injury. This study was undertaken to investigate possible endothelial-repairing effects of EPC transplantation after LPS-induced ALI in rats. Using Y-chromosome in situ hybridization and reverse transcription polymerase chain reaction assay, we detected the expression of sex-determining region y in the injured lungs of female model rats, suggesting that allogenic EPCs can migrate to the injured lung tissues. Rats that have received the EPC treatment had a reduced pulmonary edema level, inflammation, hemorrhage, and hyaline membrane formation, as well as an increased survival rate from 44% to 81%. Furthermore, anti-inflammatory cytokine IL-10 levels were dramatically increased in the EPC-treated rats compared with the phosphate buffered saline-treated rats. On the contrary, endothelin-1 and iNOS were downregulated in the EPC-treated group. These findings provide evidence that i.v. EPC treatment results in engraftment of EPCs to the injured lung tissue, which can significantly attenuate lung injury and improve survival in ALI rats. The beneficial effects of EPC engraftment is likely to come from maintaining the integrity of pulmonary alveolar-capillary barrier, reestablishing the endothelial function in vessels and ameliorating the inflammatory state.

We have shown cardiac protection by metallothionein (MT) in the development of diabetic cardiomyopathy (DCM) via suppression of cardiac cell death in cardiac-specific MT-overexpressing transgenic (MT-TG) mice. The present study was undertaken to define whether diabetes can induce cardiac endoplasmic reticulum (ER) stress and whether MT can prevent cardiac cell death via attenuating ER stress. Diabetes was induced by streptozotocin in both MT-TG and wild-type (WT) mice. Two weeks, and 2 and 5 months after diabetes onset, cardiac ER stress was detected by expression of ER chaperones, and apoptosis was detected by CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and cleaved caspase-3 and caspase-12. Cardiac apoptosis in the WT diabetic mice, but not in MT-TG diabetic mice, was significantly increased 2 weeks after diabetes onset. In parallel with apoptotic effect, significant up-regulation of the ER chaperones, including glucose-regulated protein (GRP)78 and GRP94, cleaved ATF6 and phosporylated eIF2α, in the hearts of WT, but not MT-TG diabetic mice. Infusion of angiotensin II (Ang II) also significantly induced ER stress and apoptosis in the hearts of WT, but not in MT-TG mice. Direct administration of chemical ER stress activator tunicamycin significantly increased cardiac cell death only in WT mice. Pre-treatment with antioxidants completely prevented Ang II-induced ER stress and apoptosis in the cultured cardiac cells. These results suggest that ER stress exists in the diabetic heart, which may cause the cardiac cell death. MT prevents both diabetes- and Ang II-induced cardiac ER stress and associated cell death most likely via its antioxidant action, which may be responsible for MT's prevention of DCM.