Effect of humidified high-flow nasal cannula oxygen therapy on respiratory function recovery in stable COPD patients.

OBJECTIVE: To investigate the effect of humidified high-flow nasal cannula oxygen therapy (HFNC) on the application effect and respiratory functional recovery of stable COPD patients. METHODS: The data of 116 patients with stable COPD treated in our hospital from March 2019 to January 2021 were analyzed retrospectively. Among them, 54 patients treated with conventional oxygen therapy (COT) were enrolled into the control group (CG), and the remaining 62 treated with HFNC were divided to the experimental group (EG). The clinical efficacy and adverse reactions of both groups were assessed, and the blood gas analysis indexes pH, PaO2, PaCO2, respiratory function indexes FEV1, FEV1%, FEV1/FVC, quality of life and motor recovery were compared. RESULTS: After treatment, compared with the CG, the FEV1, FEV1% and FEV1/FVC in the EG were obviously higher (P<0.05). Besides, the pH and PaO2 in the EG were markedly higher (P<0.05), while PaCO2 was lower (P<0.05). The total effective rate, SGRQ scores and 6MWT in the EG were markedly higher than those in the CG (P<0.05), while the incidence of adverse reactions in the EG was lower (P<0.05). CONCLUSION: HFNC can improve respiratory function and quality of life of stable COPD patients, with higher safety.

LncRNA CRNDE modulates cardiac progenitor cells' proliferation and migration via the miR-181a/LYRM1 axis in hypoxia.

BACKGROUND: The cardiac progenitor cells provide a valuable method for myocardial infarction related heart failure therapies. But cardiac progenitor cell quickly loses the proliferation abilities during the myocardial infarction. In this paper, we aim to explore the role of lncRNA CRNDE in the modulation of cardiac progenitor cell reproduction and migration. METHODS: Cardiac progenitor cells were isolated from neonatal adult Sprague-Dawley rats by removing the heart and homogenizing the tissue. Various siRNAs and RNA mimics were co-transfected to the cells. A list of characterization methods, including qRT-PCR, Western blotting, luciferase assay, CCK-8 assay, and EdU incorporation assay, were utilized to verify the roles and interactions of CRNDE, miR-181a, and LYRM1 in cardiac progenitor cells' proliferation and migration potentials. RESULTS: LncRNA CRNDE expressions were substantially promoted in the CoCl2-related hypoxia cardiac progenitor cell model. CRNDE suppression inhibited cardiac progenitor cell reproduction and migration under hypoxic conditions. The miR-181a-inhibitor restored the reproduction and migration potentials of cardiac progenitor cells after CRNDE knockdown in hypoxia. LYR motif containing 1 (LYRM1) was a target of miR-181a, and miR-181a negatively modulated its expressions. LYRM1 knockdowns inhibited miR-181a-inhibitor's protective effects for cardiac progenitor cell functions in hypoxia. CONCLUSIONS: Our experiments and analysis demonstrated that CRNDE could modulate cardiac progenitor cell proliferation and migration potentials via the miR-181a/LYRM1 axis in hypoxia.

MicroRNA-125a-3p participates in odontoblastic differentiation of dental pulp stem cells by targeting Fyn.

Fyn is a member of the protein tyrosine kinase family and its overexpression is associated with various types of inflammation. MicroRNAs can regulate the expression of target genes and play an important role in varied physiological and pathological processes. Based on the important role of Fyn and microRNA-125a-3p (miR-125a-3p) in inflammation, and combined with the bioinformatics studies, we performed in this study and chose miR-125a-3p as the focus of our research. During the progression of inflammation, we found that the expression of miR-125a-3p was decreased while the expression of Fyn was up-regulated. Fyn formed a complex with Neuropilin-1, which inhibited odontoblastic differentiation and expanded inflammatory responses through nuclear factor-κB signal pathways in dental pulp stem cells (DPSCs). These findings suggested that miR-125a-3p plays an important role in odontoblastic differentiation of DPSCs by targeting Fyn, implying its therapeutic potential in dental caries.

lncRNA GAS5 regulates myocardial infarction by targeting the miR-525-5p/CALM2 axis.

Long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of cardiovascular diseases, especially in myocardial infarction (MI). However, the underlying molecular mechanism of how lncRNA involves and affect MI still remains unclear. This study aimed to investigate the expression of lncRNA growth arrest-specific transcript 5 (GAS5) and its effects on myocardial cells' proliferation, cell cycle, and apoptosis. The possible mechanisms involved in GAS5, calmodulin 2 (CALM2), and microRNA (miR)-525-5p were also explored. The messenger RNA (mRNA) level of CALM2, GAS5, and miR-525-5p in postmyocardial infarction (MI) and normal cells were examined by quantitative real-time polymerase chain reaction (RT-qPCR). Western blot analysis assay was conducted to detect the protein levels of CALM2. The changes of cell cycle/apoptosis and cell viability of post-MI myocardial cells (PMMC) were determined by flow cytometry analysis and MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay after knockdown of GAS5 or CALM2, respectively. Dual luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were performed to verify the targeting relationship between miR-525-5p and GAS5, CALM2 in myocardial. Hypoxic preconditioning was performed in normal cells, which constructed a simulated MI environment, and the effect of GAS5 on cardiomyocyte apoptosis was detected. Our data showed that the expression of GAS5 and CALM2 in PMMC was significantly upregulated, while the expression of miR-525-5p was downregulated. Overexpression of GAS5 and CALM2 profoundly promoted the apoptosis of myocardial cell. However, the proliferation of myocardial cell was inhibited by the upregulation of GAS5 and CALM2. Moreover, GAS5 was proved to be the target of miR-525-5p and GAS5 downregulated the expression of miR-525-5p and CALM2. In addition, lncRNA GAS5 promotes MI, while CALM2 induced MI can be reversed by miR-525-5p. These data suggested that lncRNA GAS5 promoted the development and progression of MI via targeting of the miR-525-5p/CALM2 axis and it has the potential to be explored as a therapeutic target for the treatment of MI in the future.

Valproic acid regulates Ang II-induced pericyte-myofibroblast trans-differentiation via MAPK/ERK pathway.

Myocardial fibrosis (MF) plays an important part in cardiovascular diseases. The main cytological characteristics of MF is the increased number of myofibroblasts, which have multiple sources such as EMT, EndMT, myeloid progenitors, monocytes, and fibrocytes. Recent data showed that pericytes may represent a major source of myofibroblasts in kidney fibrosis. Valproic acid (VPA) is a kind of short-chain fatty acid. It was reported in recent studies that VPA regulates gene expression and influences various signal pathways. HDACs inhibitors can hinder the growth of tumor cells and differentiation of stem cells. And little is known about the effects of HDACs inhibitors on myofibroblasts transdiffererntiaton. This study focused on the role of HDACs in pericyte-myofibroblast trans-differentiation and how HDACs inhibitor VPA influenced proliferation, migration, viability and myofibroblast trans-differentiation of pericytes for the first time. Rat cardiac fibrosis model was induced by Ang II. Immunohistochemistry was employed to examine cardiac fibrosis and flow cytometry was used to analyze whether inflammatory cells involve VPA-induced trans-differentiation. Pericytes proliferation, migration and differentiation to myofibroblasts were performed to examine the role of VPA on pericyte trans-differentiation. Immunoblot and qPCR were applied to identify the signal transduction involving in VPA-induced trans-differentiation. In vivo study showed that HDAC inhibitor VPA blocks cardiac fibrosis, and inflammation inhibition was not involved in this process. VPA treatment inhibited Ang II pericyte proliferation, migration and transdifferentiation to myofibroblast. Furthermore, the inhibition of α-SMA expression by VPA was related to reduce phosphorylation of ERK, and a pharmacological inhibitor of MEK suppressed Ang II-induced α-SMA expression. HDAC4 knockdown resulted in inhibiting Ang II-mediated α-SMA expression as well as the phosphorylation of ERK. Moreover, the inhibitors of protein phosphatase 2A and 1 (PP2A and PP1) restored the Ang II-stimulated α-SMA expression from the inhibitory effect of VPA. Together, the current data indicate that the differentiation of pericytes to myofibroblasts is HDAC4 dependent and requires phosphorylation of ERK.

Expression pattern and functional analysis of fundc1 in rare minnow (Gobiocypris rarus).

Fundc1 is a mitochondrial outer membrane protein and plays important roles in mitochondria fission and hypoxia-induced mitophagy in mammalian cells. However, there is no relevant report of fundc1 in fish. In the present study, we cloned a 942bp fundc1 cDNA from rare minnow. The cDNA, designated as Grfundc1 cDNA, contains an open reading frame (ORF) of 459bp which encodes a polypeptide of 152 amino acid residues. Comparisons of deduced amino acid sequences demonstrated that Grfundc1 was highly homologous with those of other vertebrates. RT-PCR and real time PCR detection revealed that the transcripts of Grfundc1 were not detectable in the unfertilized eggs and had high levels at blastula and gastrula stages. Whole mount in situ hybridization analysis observed that Grfundc1 was ubiquitously expressed at early stage and later riched in specific regions, such as brain, branchial arch, eye and somite during embryogenesis. Grfundc1 was expressed in all the tissues of rare minnow adult, including brain, liver, gill, eyes, heart, kidney, intestine, muscle, testis and ovary. The expression of Grfundc1 in the brain, gill, heart and eye of rare minnow adult was significantly down-regulated by hypoxia. Similar hypoxic response was observed in the rare minnow embryos at 48hpf following hypoxia exposure. Functional analysis showed that knockdown of Grfundc1 significantly caused defects in the body axis and dorsal neural tissues of rare minnow embryos. These results indicate that Grfundc1 may play important roles in embryogenesis in fish.

A nested multiplex polymerase chain reaction assay for the differential identification of three zooanthroponotic chlamydial strains in porcine swab samples.

Porcine chlamydial infection is an enzootic infectious disease caused by multiple members of the family Chlamydiaceae (e.g. Chlamydophila abortus, Chlamydia suis, and Chlamydophila pneumoniae). Rapid and accurate differentiation of these pathogens is critical in the control and prevention of disease. The aim of the current study was to develop a nested multiplex polymerase chain reaction (nmPCR) assay to simultaneously detect the 3 chlamydial pathogens in clinical samples. In the first round of the nmPCR, 1 pair of family-specific primers were used to amplify the 1,100 base pair (bp) fragment of chlamydial ompA gene. In the second round of the nmPCR, 4 inner primers were designed for Ch. abortus, C. suis, and Ch. pneumoniae. Each pathogen produced a specific amplicon with a size of 340 bp, 526 bp, and 267 bp respectively. The assay was sensitive and specific for detecting target pathogens in both cell cultures and clinical specimens. The results, incorporated with the improved rapid DNA extraction protocol, suggest that the nmPCR could be a promising assay for differential identification of different chlamydial strains in pigs.