Regional Diversities in Fibrogenesis Weighed as a Key Determinant for Atrial Arrhythmogenesis

Atrial fibrosis plays a key role in atrial myopathy, resulting in the genesis of atrial fibrillation (AF). The abnormal distribution of fibrotic tissue, electrical coupling, paracrine interactions, and biomechanical–electrical interactions have all been suggested as causes of fibrosis-related arrhythmogenesis. Moreover, the regional difference in fibrogenesis, specifically the left atrium (LA) exhibiting a higher arrhythmogenesis and level of fibrosis than the right atrium (RA) in AF, is a key contributor to atrial arrhythmogenesis. LA fibroblasts have greater profibrotic cellular activities than RA fibroblasts, but knowledge about the regional diversity of atrial regional fibrogenesis remains limited. This article provides a comprehensive review of research findings on the association between fibrogenesis and arrhythmogenesis from laboratory to clinical evidence and updates the current understanding of the potential mechanism underlying the difference in fibrogenesis between the LA and RA.

Global and Regional Myocardial Work in Female Adolescents with Weight Disorders

Background: Anorexia nervosa (AN) and obesity (OB) lead to changes in SBP (i.e., loading conditions) that may affect left ventricular (LV) myocardial work (MW). The novel concept of LV pressure-strain loops allows non-invasive estimation of MW, this latter being correlated with cardiac energy metabolism. In addition, the study of regional MW can detect subtle alterations in cardiac function by highlighting an abnormal distribution of MW. Objective: The aim of this study was to assess the cardiac function of AN and OB patients by evaluating global and regional LV strains and MW. Methods: Eighty-seven female adolescents, comprising 26 with AN (14.6 ± 1.9 yrs. old), 28 with OB (13.2 ± 1.4 yrs. old), and 33 controls (14.0 ± 2.0 yrs. old) underwent speckle-tracking echography to assess global and regional LV strains and MW. Results: SBP was higher in adolescents with obesity than in AN patients or controls. Global MW was similar between groups. In AN patients and controls, longitudinal strains were higher at the apex than at the base of the LV, whereas they were similar in obesity patients, owing to a decrease in their apical longitudinal strain. Consequently, their MW was higher at the basal level than either of the other two groups (1854 ± 272 vs. 1501 ± 280 vs. 1575 ± 295 mmHg% in OB patients, AN patients, and controls, respectively. Conclusion: Despite altered SBP, the global MW of adolescents with weight disorders was unaffected. However, in adolescents with obesity, the distribution of their regional LV MW was altered, which might reflect specific regional remodeling.

Vapor cannabis exposure generationally affects male reproductive functions in mice

This study was performed to examine whether vapor exposure to cannabis plant matter negatively impacts male reproductive functions and testis development in mice. Adult CD-1 male mice (F0) were exposed to air (control) or 200 mg of vaporized cannabis plant matter 3x/day over a 10 day period. Subsequently, F0 males were bred with drug naive CD-1 females to generate F1 males, and F1 offspring were used to generate F2 males. Cannabis vapor exposure decreased sperm count and/or motility in F0 and F1 males and disrupted the progression of germ cell development, as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis in F0 males. Although plasma levels of testosterone were not affected by cannabis exposure in any ages or generations of males, dysregulated steroidogenic enzymes, Cyp11a1 and Cyp19a1, were observed in F0 testis. In the neonatal testis from F1 males, while apoptosis was not altered, DNA damage and DNMT1, but not DNMT3A and DNMT3B, were increased in germ cells following cannabis exposure. In contrast, the alterations of DNA damage and DNMT1 expression were not observed in F2 neonatal males. These results suggest that cannabis vapor exposure generationally affects male reproductive functions, probably due to disruption of spermatogenesis in the developing testis.

Involvement of JAK-STAT-SOCS3 Pathway in the Regression of Mice X-Zone of Adrenal Cortex

Previously, we showed that the histological markers of the mice X-zone of adrenal cortex were still present in adult male and female postpartum SF1/SOCS3KO mice. Abnormal distribution of lipid droplets along the adrenal cortex and reduced ACTH-induced corticosterone secretion were observed in SF1/SOCS3KO mice (1). Here we have examined the adrenals of the SF1/SOCS3KO male and virgin female at 3, 8, 15 and 30 weeks through morphological and molecular analysis. Hematoxylin-eosin stains showed X-zone retention in the SF1/SOCS3KO mice adrenals regardless of the postnatal age analyzed. CYP17A1-positive cells were immunolocalized in the X-zone of SF1/SOCS3KO mice that were confirmed by immunoblotting. A fetal adrenal enhancer (FAdE) and Pik3c2g and 20αHSD genes expression were analyzed by RT-PCR, and these genes were present in the male SF1/SOCS3KO mice up to the age of 8 and 15 weeks, but not in the control mice. Therefore, we showed retention of X-zone in the adrenal cortex of SOCS3KO mice up to the age of 30 week, which suggest the involvement of JAK/STAT/SOCS3 signaling pathway in the differentiation process of adrenal cortex. Reference: (1) Pedroso et al., J Endocrinol.2017 Dec;235(3):207–222.

The Effects of the Supplementation with Snakehead Fish and Sea Cucumber Extracts on Platelet-Derived Growth Factor in Post-Operative Patients

Wound healing is a complex process that involves the interaction between Extracellular Matrix (ECM) cells and mediated by cytokines and various growth factors, especially platelet-derived growth factor (PDGF) which plays a role in almost every phase of wound healing. Applying snakehead fish and sea cucumber extract containing amino acids and fatty acids in post-operative patients is expected to increase PDGF levels and enable the acceleration of the wound healing process. This study was a double-blind randomized control trial with a pre and post-treatment approach which involved 34 post-operative patients divided into two groups; the control group (K1) and treatment group (K2) and was carried out from April to June 2019 at Dr. Moewardi Hospital in Surakarta. Independent sample T-test was used for data with normal distribution to determine the mean differences between the control and treatment groups, while the Mann-Whitney test was used for data with the abnormal distribution. Also, to determine the mean difference before and after the treatment of one paired group, a paired T-test was used for data with normal distribution, while the Wilcoxon test was used for data with the abnormal distribution. p < 0.05 was significant with 95% Confidence Intervals (CI). The supplementation of snakehead fish and sea cucumber extract significantly increased PDGF levels in the treatment group (K2) compared to the controls group (K1) (p <0.001). Our findings showed that snakehead fish and sea cucumber extract were able to increase PDGF levels in post-operative patients on the fourth day.