Arginine attenuates chronic mountain sickness in rats via microRNA-144-5p.

Hypobaric hypoxia is an environmental stress leading to high-altitude pulmonary hypertension. While high-altitude pulmonary hypertension has been linked to high hematocrit findings (chronic mountain sickness; CMS). The present study is designed to investigate the effect of arginine (ARG) on hypobaric hypoxia-induced CMS of rats. Hypobaric hypoxia resulted in lower body weight, decreased appetite, increased pulmonary artery pressure, and deteriorated lung tissue damage in rats. Red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin values and blood viscosity were increased in rats, which were alleviated by ARG. microRNA (miRNA) microarray analysis was used to filter differentially expressed miRNAs after ARG in rats. miR-144-5p was reduced under hypobaric hypoxia and upregulated by ARG. miR-144-5p silencing aggravated the erythrocytosis and hyperviscosity in rats, and also accentuated tissue damage and excessive accumulation of RBC. The role of miR-144-5p in rats with CMS was achieved by blocking erythropoietin (EPO)/erythropoietin receptor (EPOR). In conclusion, ARG alleviated CMS symptoms in rodents exposed to hypobaric hypoxia by decreasing EPO/EPOR via miR-144-5p.

Exosomal microRNA-98-5p from hypoxic bone marrow mesenchymal stem cells inhibits myocardial ischemia-reperfusion injury by reducing TLR4 and activating the PI3K/Akt signaling pathway.

OBJECTIVE: MicroRNAs (miRNAs) are essential biomarkers during development of human diseases. We aimed to explore the role of hypoxia-induced bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-98-5p in myocardial ischemia-reperfusion injury (MI/RI). METHODS: BMSCs were isolated, cultured, stimulated by hypoxia and transfected with adenovirus expressing miR-98-5p. The exosomes were extracted from BMSCs and named as BMSC-exos. The rat MI/RI models were established by ligation of left anterior descending artery and were respectively injected. Then, hemodynamic indices, myocardial enzymes, oxidative stress factors, inflammatory factors, macrophage infiltration and infarct size in these rats were determined. Expression of miR-98-5p, toll-like receptor 4 (TLR4) and the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway-related proteins was assessed. The target relation between miR-98-5p and TLR4 was confirmed by bioinformatic method and dual luciferase report gene assay. RESULTS: MiR-98-5p was downregulated, TLR4 was upregulated and the PI3K/Akt signaling pathway was inactivated in MI/RI rat myocardial tissues. Exosomal miR-98-5p from hypoxic BMSCs promoted cardiac function and suppressed myocardial enzyme levels, oxidative stress, inflammation response, macrophage infiltration and infarct size in I/R myocardial tissues. Moreover, TRL4 was targeted by miR-98-5p and miR-98-5p activated PI3K/Akt signaling pathway. CONCLUSION: Hypoxia-induced BMSC-exos elevated miR-98-5p to protect against MI/RI. This study may be helpful for treatment of MI/RI.

The efficacy of therapeutic apheresis in patients with refractory neuromyelitis optica spectrum disorders: a single-center retrospective study.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are associated with recurrent episodes of optic neuritis and transverse myelitis, often resulting in high attack-related disability. Therapeutic apheresis has been recommended as a second-line treatment for steroid-refractory NMOSD. To assess the efficacy and safety of two apheresis techniques, lymphoplasmapheresis (LPE) and therapeutic plasma exchange (TPE), in refractory NMOSD and to provide a new treatment option for patients with refractory NMOSD. METHODS: This retrospective study examined NMOSD patients who had undergone either LPE or TPE treatment between January 2015 and January 2018. The patients were monitored for improvements in disabilities, incidences of adverse reactions, and safety of the procedure over a one-year follow-up period. The primary outcome measures included changes in the visual outcome scale (VOS) score, the expanded disability status scale (EDSS), and the annualized relapse rate (ARR). RESULTS: Neurological function and objective response rates were significantly improved in 76.5% of patients treated with LPE and 83.3% of patients treated with TPE. There were no significant differences in the two treatment groups (P=0.392). Similarly, there were no differences in the reduction in the relative relapse rate between the two groups (P=0.494). Adverse reactions, mostly of mild or moderate intensity, were recorded in 9.3% of procedures in 38% of patients. The most commonly observed adverse events (AEs) were similar between the two treatment cohorts. CONCLUSIONS: Patients treated with LPE showed improved neurological function comparable to that reported with TPE treatment. No superiority was shown for either of the apheresis techniques.

[A Predictive Model for Hemoglobin Change before and after Collection of Apheresis Autologous Red Blood Cells in Patients].

OBJECTIVE: To analyze the affecting factors of hemoglobin changes in apheresis red blood cells (RBCs), and to establish a predictive model for the evaluation of apheresis. METHODS: The clinical data of 130 patients undergoing selective surgery for apheresis autologous RBCs from January 2017 to December 2018 were collected. The change of hemoglobin and its affecting factors before and after apheresis were analyzed. The predictive model of the hemoglobin change was established by machine learning algorithm and compared with the theoretical predictive model. RESULTS: The average Hb level in the 300 ml autologous RBC group decreased by 22.61±8.85 g/L, and the average Hb in 400 ml group decreased by 29.08±7.25 g/L. The change of Hb was mainly affected by Hb level before apheresis and peripheral circulation blood volume (P＜0.05). Sex, age, and the interval time between blood collection and operation not significantly influenced Hb change (P＞0.05). The initially established predictive model by the machine learning (MAE 6.27) is superior to the theoretical predictive model (MAE 8.11). CONCLUSION: The predictive model established by the machine learning can provide a reference for more accurate evaluation of apheresis autologous red blood cells.

Octreotide inhibits the proliferation of gastric cancer cells through P300-HAT activity and the interaction of ZAC and P300.

Somatostatin (SST) exhibits a wide range of physiological functions, including the regulation of tumor cell growth. Octreotide (OCT) is a synthetic analogue of SST that can be used to slow gastrointestinal bleeding, inhibit the release of growth hormone and impede gastrointestinal tumor growth. The aim of the present study was to investigate the molecular mechanism of OCT underlying the inhibition of gastric cancer cell proliferation. Proteins of interest were detected using western blotting, and the zinc finger protein (ZAC)-P300 complex was quantified using co-immunoprecipitation. P300-histone acetyltransferase (P300-HAT) activity was determined spectrophotometrically. The results showed that OCT decreased the phosphorylation of Akt which caused the level of ZAC to increase. In turn, the interaction between ZAC and P300 increased the activity of P300-HAT; ultimately, the phosphorylation of serine 10 in histone H3 (pS10-H3) was decreased and the acetylation of lysine 14 in histone H3 (acK14-H3) was increased. These results suggest that OCT attenuates SGC-7901 cell proliferation by enhancing P300-HAT activity through the interaction of ZAC and P300, causing a reduction in pS10-H3 and an increase in acK14-H3. These findings provide insight for future research on OCT and further demonstrate the potential of OCT to be used as a therapeutic agent for gastric cancer.