Momordicine I alleviates isoproterenol-induced cardiomyocyte hypertrophy through suppression of PLA2G6 and DGK-ζ.

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 µM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, ß-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 µg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy. Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.

Proprotein convertase subtilisin/kexin type 9 inhibitor non responses in an adult with a history of coronary revascularization: A case report.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder that is characterized by severely increased low-density lipoprotein (LDL) cholesterol levels. At the same time, elevated LDL levels accelerated the development of coronary heart disease. Several classes of drugs are currently in use to treat FH. Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is novel one of these. CASE SUMMARY: This manuscript reports a case of FH that responded modestly after treatment with PCSK9i and statin drugs. Of even more concern is that the patient frequently admitted to the hospital during a 12-year follow-up period. Subsequently, we identified a heterozygous mutation, 1448G>A (W483X) of the LDL receptor (LDLR) in this patient. The serum levels of PCSK9 (proprotein convertase subtilisin/kexin type 9) in the patient was 71.30 ± 26.66 ng/mL, which is close the average level reported in the literature. This LDLR mutation affects LDLR metabolism or structure, which may make it unsuitable for use of PCSK9i. CONCLUSION: Our outcome demonstrates that LDLR-W483X represents a partial loss-of-function LDLR and may contribute to PCSK9i ineffective. In the meanwhile, additional measures are therefore required (particularly with gene sequencing or change the treatment plan) must be initiated as early as possible. Genetic testing for clinically challenging cases who do not respond to PCSK9i therapy is very helpful.

Nuclear Alarmin Cytokines in Inflammation.

Pathogen-associated molecular patterns (PAMPs) are some nonspecific and highly conserved molecular structures of exogenous specific microbial pathogens, whose products can be recognized by pattern recognition receptor (PRR) on innate immune cells and induce an inflammatory response. Under physiological stress, activated or damaged cells might release some endogenous proteins that can also bind to PRR and cause a harmful aseptic inflammatory response. These endogenous proteins were named damage-associated molecular patterns (DAMPs) or alarmins. Indeed, alarmins can also play a beneficial role in the tissue repair in certain environments. Besides, some alarmin cytokines have been reported to have both nuclear and extracellular effects. This group of proteins includes high-mobility group box-1 protein (HMGB1), interleukin (IL)-33, IL-1α, IL-1F7b, and IL-16. In this article, we review the involvement of nuclear alarmins such as HMGB1, IL-33, and IL-1α under physiological state or stress state and suggest a novel activity of these molecules as central initiators in the development of sterile inflammation.

Genome-wide identification of the fatty acid desaturases gene family in four Aspergillus species and their expression profile in Aspergillus oryzae.

Fatty acid desaturases play a key role in producing polyunsaturated fatty acids by converting single bonds to double bonds. In the present study, a total of 13, 12, 8 and 8 candidate fatty acid desaturases genes were identified in the Aspergillus oryzae, Aspergillus flavus, Aspergillus fumigatus and Aspergillus nidulans genomes through database searches, which were classified into five different subfamilies based on phylogenetic analysis. Furthermore, a comprehensive analysis was performed to characterize conserved motifs and gene structures, which could provide an intuitive comprehension to learn the relationship between structure and functions of the fatty acid desaturases genes in different Aspergillus species. In addition, the expression pattern of 13 fatty acid desaturases genes of A. oryzae was tested in different growth stages and under salt stress treatment. The results revealed that the fatty acid desaturases genes in A. oryzae were highly expressed in adaptive phase growth and up-regulated under salt stress treatment. This study provided a better understanding of the evolution and functions of the fatty acid desaturases gene family in the four Aspergillus species, and would be useful for seeking methods to improve the production of unsaturated fatty acids and enhance efforts for the genetic improvement of strains to adapt to the complex surrounding environment.