Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.

Objective: To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods: From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results: A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10-10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions: The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

Integrated genomics analysis highlights important SNPs and genes implicated in moderate-to-severe asthma based on GWAS and eQTL datasets.

BACKGROUND: Severe asthma is a chronic disease contributing to disproportionate disease morbidity and mortality. From the year of 2007, many genome-wide association studies (GWAS) have documented a large number of asthma-associated genetic variants and related genes. Nevertheless, the molecular mechanism of these identified variants involved in asthma or severe asthma risk remains largely unknown. METHODS: In the current study, we systematically integrated 3 independent expression quantitative trait loci (eQTL) data (N = 1977) and a large-scale GWAS summary data of moderate-to-severe asthma (N = 30,810) by using the Sherlock Bayesian analysis to identify whether expression-related variants contribute risk to severe asthma. Furthermore, we performed various bioinformatics analyses, including pathway enrichment analysis, PPI network enrichment analysis, in silico permutation analysis, DEG analysis and co-expression analysis, to prioritize important genes associated with severe asthma. RESULTS: In the discovery stage, we identified 1129 significant genes associated with moderate-to-severe asthma by using the Sherlock Bayesian analysis. Two hundred twenty-eight genes were prominently replicated by using MAGMA gene-based analysis. These 228 replicated genes were enriched in 17 biological pathways including antigen processing and presentation (Corrected P = 4.30 × 10- 6), type I diabetes mellitus (Corrected P = 7.09 × 10- 5), and asthma (Corrected P = 1.72 × 10- 3). With the use of a series of bioinformatics analyses, we highlighted 11 important genes such as GNGT2, TLR6, and TTC19 as authentic risk genes associated with moderate-to-severe/severe asthma. With respect to GNGT2, there were 3 eSNPs of rs17637472 (PeQTL = 2.98 × 10- 8 and PGWAS = 3.40 × 10- 8), rs11265180 (PeQTL = 6.0 × 10- 6 and PGWAS = 1.99 × 10- 3), and rs1867087 (PeQTL = 1.0 × 10- 4 and PGWAS = 1.84 × 10- 5) identified. In addition, GNGT2 is significantly expressed in severe asthma compared with mild-moderate asthma (P = 0.045), and Gngt2 shows significantly distinct expression patterns between vehicle and various glucocorticoids (Anova P = 1.55 × 10- 6). CONCLUSIONS: Our current study provides multiple lines of evidence to support that these 11 identified genes as important candidates implicated in the pathogenesis of severe asthma.

Effects of Ca2+-activated potassium and inward rectifier potassium channel on the differentiation of endothelial progenitor cells from human peripheral blood.

Endothelial progenitor cells (EPCs) are bone marrow-derived cells that have the propensity to differentiate into mature endothelial cells (ECs). The transplantation of EPCs has been shown to enhance in vivo postnatal neo-vasculogenesis, as well as repair infarcted myocardium. Via the whole-cell patch clamp technique, numerous types of ion channels have been detected in EPCs, including the inward rectifier potassium channel (IKir), Ca2+-activated potassium channel (IKCa), and volume-sensitive chloride channel, but their influence on the differentiation of EPCs has yet to be characterized. The present study was designed to investigate: (1) which ion channels have the most significant impact on the differentiation of EPCs; (2) what role ion channels play in the functional development of EPCs; (3) the mRNA and protein expression levels of related ion channel subunits in EPCs. In our study, EPCs were obtained from the peripheral blood of healthy adults and cultured with endothelial growth factors. When EPCs differentiate into mature ECs, they lose expression of the stem cell/progenitor marker CD133, as analyzed by flow cytometry (0.44±0.20 %). However, treatment with the potassium channel inhibitor, tetraethylammonium (TEA) results in an increase in CD133+ cells (25.50±7.55 %). In a functional experiment, we observed a reduction in the capacity of TEA treated ECs (differentiated from EPCs) to form capillary tubes when seeded in Matrigel. At the mRNA and protein levels, we revealed several K+ subtypes, including KCNN4 for IKCa, KCNNMA1 for BKCa and Kir3.4 for IKir. These results demonstrate for the first time that potassium channels play a significant role in the differentiation of EPCs. Moreover, inhibition of potassium channels may depress the differentiation of EPCs and the significant potassium channel subunits in EPCs appear to be IKCa, BKCa and Kir3.4.

SYNPO2 promotes the development of BLCA by upregulating the infiltration of resting mast cells and increasing the resistance to immunotherapy.

Synaptopodin 2 (SYNPO2) plays a pivotal role in regulating tumor growth, development and progression in bladder urothelial Carcinoma (BLCA). However, the precise biological functions and mechanisms of SYNPO2 in BLCA remain unclear. Based on TCGA database­derived BLCA RNA sequencing data, survival analysis and prognosis analysis indicate that elevated SYNPO2 expression was associated with poor survival outcomes. Notably, exogenous SYNPO2 expression significantly promoted tumor invasion and migration by upregulating vimentin expression in BLCA cell lines. Enrichment analysis revealed the involvement of SYNPO2 in humoral immune responses and the PI3K/AKT signaling pathway. Moreover, increased SYNPO2 levels increased the sensitivity of BLCA to PI3K/AKT pathway­targeted drugs while being resistant to conventional chemotherapy. In in vivo BLCA mouse models, SYNPO2 overexpression increased pulmonary metastasis of 5637 cells. High SYNPO2 expression led to increased infiltration of innate immune cells, particularly mast cells, in both nude mouse model and clinical BLCA samples. Furthermore, tumor immune dysfunction and exclusion score showed that patients with BLCA patients and high SYNPO2 expression exhibited worse clinical outcomes when treated with immune checkpoint inhibitors. Notably, in the IMvigor 210 cohort, SYNPO2 expression was significantly associated with the population of resting mast cells in BLCA tissue following PD1/PDL1 targeted therapy. In conclusion, SYNPO2 may be a promising prognostic factor in BLCA by modulating mast cell infiltration and exacerbating resistance to immune therapy and conventional chemotherapy.

Severe intracranial infection caused by community-acquired hypervirulent Klebsiella pneumoniae: A case report.

Hypervirulent Klebsiella pneumoniae (HvKp) is a dynamic pathotype characterized by heightened mucoviscosity and virulence, typically afflicting individuals within the community, who commonly exhibit good health. We presented a case study of a 65-year-old male with diabetes who developed community acquired pneumonia, septic shock, and intracranial infection. The diagnosis was established through cranial magnetic resonance imaging (MRI), typical clinical presentation, and biological culture. The presence of HvKp infection was confirmed by cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) and blood culture. Treatment consisted of Amikacin 0.8 g qd in combination with meropenem 2.0 g q8h, based on drug sensitivity testing. The patient experienced symptom relief, with the CSF becoming clear and the elimination of the pathogen, ultimately resulting in a successful recovery. The clinical data, diagnosis, and treatment of the patient were documented, and a review of the literature was conducted to offer clinical guidance regarding the intracranial infection resulting from community-acquired HvKp.

Clinical efficacy and safety of high-flow nasal cannula (HFNC) in acute hypoxaemic patients with COVID-19: a protocol for a systematic review and meta-analysis.

INTRODUCTION: When COVID-19 patients develop hypoxaemic respiratory failure, they often undergo early intubation. Such a potentially aerosol-generating approach places caregivers at increased risk of contracting COVID-19. This protocol aims to evaluate the clinical efficacy and safety of a high-flow nasal cannula (HFNC) for the treatment of COVID-19 patients with acute hypoxaemic respiratory failure. METHODS AND ANALYSIS: We intend to search MEDLINE, Embase, Web of Science and Cochrane Library to identify all randomised controlled trials (RCTs) on the use of HFNC in COVID-19 patients with acute respiratory failure. We will screen the RCTs against eligibility criteria for inclusion in our review. Two reviewers will independently undertake RCT selection, data extraction and risk of bias assessment. Primary outcome will be the rate of intubation, and secondary outcomes will be intensive care unit (ICU)/hospital mortality, ICU/hospital length of stay and risks of infection transmission. We will conduct meta-analyses to determine the risk ratio for dichotomous data and the mean difference (MD) or standardised MD for continuous data. Subgroup analyses will be performed based on the different quality of studies, different levels of disease severity, and the age and sex of participants. ETHICS AND DISSEMINATION: Ethical approval is not required for this study considering this is a systematic review protocol that uses only published data. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42021236519.

Long Non-coding RNA H19 Augments Hypoxia/Reoxygenation-Induced Renal Tubular Epithelial Cell Apoptosis and Injury by the miR-130a/BCL2L11 Pathway.

Acute kidney injury (AKI) is a severe kidney disease defined by partial or abrupt loss of renal function. Emerging evidence indicates that non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs), function as essential regulators in AKI development. Here we aimed to explore the underlying molecular mechanism of the lncRNA H19/miR-130a axis for the regulation of inflammation, proliferation, and apoptosis in kidney epithelial cells. Human renal proximal tubular cells (HK-2) were induced by hypoxia/reoxygenation to replicate the AKI model in vitro. After treatment, the effects of LncRNA H19 and miR-130a on proliferation and apoptosis of HK-2 cells were investigated by CCK-8 and flow cytometry. Meanwhile, the expressions of LncRNA H19, miR-130a, and inflammatory cytokines were detected by qRT-PCR, western blot, and ELISA assays. The results showed that downregulation of LncRNA H19 could promote cell proliferation, inhibit cell apoptosis, and suppress multiple inflammatory cytokine expressions in HK-2 cells by modulating the miR-130a/BCL2L11 pathway. Taken together, our findings indicated that LncRNA H19 and miR-130a might represent novel therapeutic targets and early diagnostic biomarkers for the treatment of AKI.

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have exhibited great potential in the therapy of cardiovascular disease. However, the application of MSCs is hampered by apoptosis, which reduces the number of cells in the host cardiac microenvironment. Ulinastatin (UTI), a broad­spectrum protease inhibitor that can be purified from human urine, has attracted attention for its protective effects through its immunomodulatory and anti­inflammatory properties. The present study aimed to evaluate the effects of UTI on serum deprivation­induced apoptosis of MSCs and investigate its molecular mechanisms. Cell viability was determined by the MTT assay. Apoptosis was assessed by flow cytometric analysis with Annexin V/propidium iodide staining. The protein levels of cleaved caspase­3, B­cell lymphoma­2 (Bcl­2) family proteins, total­Akt and phospho­Akt were evaluated by western blot. The results of the present study demonstrated that UTI exhibited a protective effect in serum deprived MSCs, as indicated by increased cell viability, and a reduction in the rate of apoptosis and caspase­3 activation. In addition, treatment with UTI significantly decreased the expression levels of Bcl­2, Bcl­extra large and Bcl­associated X protein. Furthermore, activation of the Akt signaling pathway was involved in the UTI­induced anti­apoptotic effects. The present findings indicated that UTI is able to promote the survival of MSCs under serum deprivation conditions. The present study may be helpful in improving the therapeutic efficacy of MSC transplantation used to cure chronic ischemic heart disease.

Challenges in diagnosing community-acquired carbapenem-susceptible Acinetobacter baumannii enterogenic sepsis: A case report.

INTRODUCTION: Community-acquired (CA) carbapenem-susceptible Acinetobacter baumannii (CSAB) enterogenic sepsis is very rare but has a high mortality. Although CA A. baumannii bloodstream infections have been known to develop from respiratory tract, urinary tract, and intravenous device-related infections, CA A. baumannii bloodstream infections from the gastrointestinal tract have not yet been reported. PATIENT CONCERNS: A 73-year-old male with the chief presentation of gastrointestinal symptoms was initially diagnosed with acute gastroenteritis and showed poor clinical response to empirical antibiotic therapy. DIAGNOSES: The diagnosis of CSAB enterogenic sepsis was established based on results of blood culture, elevated serum procalcitonin level, and specific hemodynamic changes related to septic shock. INTERVENTIONS: The patient initially received empirical antibiotic treatment (cefodizime 2.0 q12 hours plus moxifloxacin 0.4 qd); then, treatment was changed to the conventional dose of carbapenem (imipenem 0.5 q6 hour). OUTCOMES: Finally, CSAB was eliminated from the bloodstream, and the patient was discharged. LESSONS: Although severe, CA CSAB enterogenic sepsis is often misdiagnosed because of its clinical rarity. Early diagnosis and appropriate initial empirical antibiotic therapy are crucial for treating such cases.