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Mitochondria are highly dynamic organelles undergoing cycles of fusion and fission to modulate their morphology, distribution, and function, which are referred as ‘mitochondrial dynamics’. Dynamin-related protein 1 (Drp1) is known as the major pro-fission protein whose activity is tightly regulated to clear the damaged mitochondria via mitophagy, ensuring a strict control over the intricate process of cellular and organ dynamics in heart. Various posttranslational modifications (PTMs) of Drp1 have been identified including phosphorylation, SUMOylation, palmitoylation, ubiquitination, S-nitrosylation, and O-GlcNAcylation, which implicate a role in the regulation of mitochondrial dynamics. An intact mitochondrial homeostasis is critical for heart to fuel contractile function and cardiomyocyte metabolism, while defects in mitochondrial dynamics constitute an essential part of the pathophysiology underlying various cardiovascular diseases (CVDs). In this review, we summarize current knowledge on the critical role of Drp1 in the pathogenesis of CVDs including endothelial dysfunction, smooth muscle remodeling, cardiac hypertrophy, pulmonary arterial hypertension, myocardial ischemia–reperfusion, and myocardial infarction. We also highlight how the targeting of Drp1 could potentially contribute to CVDs treatments.

MORF4-related gene on chromosome 15 (MRG15), a chromatin remodeller, is evolutionally conserved and ubiquitously expressed in mammalian tissues and cells. MRG15 plays vital regulatory roles in DNA damage repair, cell proliferation and division, cellular senescence and apoptosis by regulating both gene activation and gene repression via associations with specific histone acetyltransferase and histone deacetylase complexes. Recently, MRG15 has also been shown to rhythmically regulate hepatic lipid metabolism and suppress carcinoma progression. The unique N-terminal chromodomain and C-terminal MRG domain in MRG15 synergistically regulate its interaction with different cofactors, affecting its functions in various cell types. Thus, how MRG15 elaborately regulates target gene expression and performs diverse functions in different cellular contexts is worth investigating. In this review, we provide an in-depth discussion of how MRG15 controls multiple physiological and pathological processes.

Objective： To explore the effects of down-regulated tryptase expression in mast cells on the synthesis and release of interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α） of vascular endothelial cells. Methods： Tryptase-siRNA （small-interfering RNA） vector was constructed to inhibit tryptase expression in P815 cells. The medium of P815 cells treated by the tryptase-siRNA （RNAi-P815 group） or pure vector （P815 group） was collected and used to culture bEnd.3 cells. The messenger RNAs （mRNAs） of IL-6 and TNF-α in bEnd.3 cells and their protein levels in the medium were measured by reverse transcription polymerase chain reaction （RT-PCR） and enzyme-linked immunosorbent assay （ELISA）, respectively. Results： IL-6 and TNF-α mRNAs in bEnd.3 cells cultured in RNAi-P815-conditioned medium decreased significantly compared to those in P815-conditioned medium. Consistently, lL-6 and TNF-α protein levels in the medium of bEnd.3 of RNAi-P815 group were lower than those of P815 group. Conclusion： Reduced tryptase expression significantly inhibited the synthesis and release of IL-6 and TNF-α in vascular endothelial cells. RNA interference targeting tryptase expression may be a new anti-inflammatory strategy for vascular diseases.

Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells （iPSCs） are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future.

To explore the effects of down-regulated tryptase expression in mast cells on the synthesis and release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) of vascular endothelial cells. Tryptase-siRNA (small-interfering RNA) vector was constructed to inhibit tryptase expression in P815 cells. The medium of P815 cells treated by the tryptase-siRNA (RNAi-P815 group) or pure vector (P815 group) was collected and used to culture bEnd.3 cells. The messenger RNAs (mRNAs) of IL-6 and TNF-α in bEnd.3 cells and their protein levels in the medium were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. IL-6 and TNF-α mRNAs in bEnd.3 cells cultured in RNAi-P815-conditioned medium decreased significantly compared to those in P815-conditioned medium. Consistently, IL-6 and TNF-α protein levels in the medium of bEnd.3 of RNAi-P815 group were lower than those of P815 group. Reduced tryptase expression significantly inhibited the synthesis and release of IL-6 and TNF-α in vascular endothelial cells. RNA interference targeting tryptase expression may be a new anti-inflammatory strategy for vascular diseases.[PUBLICATION ABSTRACT]

[5] A meta-analysis showed that for every 10 g/L decrease in the serum albumin concentration in critically ill patients, there was a 137% increase in in-hospital mortality, an 89% increase in the incidence of comorbidities, and a 72% increase in the length of hospital stay. Inappropriate use of HSA will cause adverse effects and increase medical costs inevitably, whereas guidance from clinical pharmacists or hospital standards can help reduce inappropriate HSA use by 30% and decrease medical costs without affecting patient prognosis. After discussion, the experts agreed that HSA has been widely used for fluid resuscitation and albumin supplementation in critically ill patients, but controversy persists regarding the applicable population, timing, and administration regimen. [...]considering the current practices in clinical diagnosis and treatment as well as existing reports, the writing group believed that it was both necessary and possible to develop an expert consensus and provide recommendations to promote the appropriate and standardized use of HSA in critical care medicine. [8] A subgroup analysis of patients with severe sepsis revealed a decreasing trend of mortality among patients receiving HSA treatment (risk ratio [RR]: 0.87, 95% confidence interval [CI]: 0.74–1.02).

Background Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut‐lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. Body This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut‐lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed. Conclusion The gut‐lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.

ω-Transaminase (ω-TA) is an attractive alternative to metal catalysts for the stereoselective amination of prochiral ketones. The narrow substrate scope of an R-ω-transaminase from Mycobacterium vanbaalenii (MvTA) limits its application in R-amine synthesis. A fluorescence-based TA activity screening system was developed to extend its substrate scope. The reactions were conducted in microtiter plates (MTPs) and displayed low background interference, high sensitivity (μM magnitude), and a wide dynamic range (ɀ-factor > 0.9). A KnowVolution campaign was performed on this enzyme, and screening ~ 8000 clones with this fluorescence-based screening system resulted in two beneficial substitutions (G68Y and F129A) and three improved variants (M3, M4, and M5). The best variant, MvTA M5 (WT+G68Y+F129A), achieved the highest catalytic efficiency (toward fluorogenic substrate NMA) which was 3.2-fold higher than that of the WT enzyme. MvTA M5 exhibited significantly enhanced activity toward six different prochiral ketones with e.e. > 99% (R). The specific activity of MvTA M5 was more than 100 times higher than that of the WT enzyme toward acetonaphthone (M5: 8.1 U/mg, WT: ~ 0.07 U/mg), and it showed the highest activity on acetonaphthone, p-ethylacetophenone, and phenylacetone.