Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Psittacosis caused severe community-acquired pneumonia accompanied by acute hypoxic respiratory failure: a multicenter retrospective cohort study from China.

INTRODUCTION: Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). METHODS: This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. RESULTS: This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. CONCLUSION: Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Risk factors of in-hospital mortality in patients with pneumocystis pneumonia diagnosed by metagenomics next-generation sequencing.

Objectives: The metagenomic next-generation sequencing (mNGS) test is useful for rapid and accurate detection and identification of pathogenic microorganisms. The aim of the present study was to investigate the factors associated with in-hospital mortality in pneumocystis pneumonia (PCP) patients with mNGS-assisted diagnosis. Methods: Our study enrolled 154 patients with mNGS-positive PCP from August 2018 to February 2022 at the First Affiliated Hospital of Zhengzhou University respectively. Patients were divided into the survivor group (n=98) and the death group (n=56) according to whether in-hospital death occurred. Baseline characteristics, patients' pre-hospital symptoms and patients' CT imaging performance during hospitalization were carefully compared between the two groups. Risk factors for the occurrence of in-hospital death were sought by selecting indicators that were significantly different between the two groups for modelling and performing multiple logistic regression analysis. Results: Compared with the in-hospital death patients, the survivors were younger and had higher levels of albumin (ALB) (age: 50.29 ± 14.63 years vs 59.39 ± 12.27 years, p<0.001; ALB: 32.24 ± 5.62 g/L vs 29.34 ± 5.42g/L, p=0.002; respectively), while the levels of lactate dehydrogenase (LDH) and C-reactive protein CRP were lower (LDH: 574.67 ± 421.24 U/L vs 960.80 ± 714.94 U/L, p=0.001; CRP: 54.97 ± 55.92 mg/L vs80.45 ± 73.26 mg/L, p=0.018; respectively). Multiple logistic regression analysis revealed that age, the baseline LDH and CRP levels were all positively associated with high in-hospital mortality [age: OR(95%CI): 1.115 (1.062-1.172), p<0.001; LDH: OR(95%CI): 1.002 (1.001-1.003), p<0.001; CRP: OR(95%CI): 1.008 (1.000-1.017), p=0.045; respectively] while the platelet counts was negatively associated with it [OR(95%CI): 0.986 (0.979-0.992), p<0.001]. Conclusions: Old age, high baseline levels of LDH and CRP and low platelet counts were risk factors of the in-hospital mortality in mNGS positive PCP patients.

The largest Se-4f cluster incorporated polyoxometalate with high Lewis acid-base catalytic activity.

A 4p-4f cluster incorporated polyoxometalate (POM), namely, H18{[(H4pic)4Eu10Se13O28(H2O)12](α-GeW9O34)4·40H2O (1-Eu, H4pic = isonicotinic acid), has been first synthesized and characterized. 1-Eu features an interesting four-shell structure, representing the largest Se-4f cluster incorporated POM known to date. Besides, 1-Eu exhibits excellent Lewis acid-base catalytic activity and reusablity in catalyzing the gram-scale dehydration condensation reaction of hydrazines and 1,3-diketones to synthesize polysubstituted pyrazoles.

Long non-coding RNA MALAT1 exacerbates acute respiratory distress syndrome by upregulating ICAM-1 expression via microRNA-150-5p downregulation.

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury in which severe inflammatory responses induce cell apoptosis, necrosis, and fibrosis. This study investigated the role of lung adenocarcinoma transcript 1 (MALAT1) in ARDS and the underlying mechanism involved. The expression of MALAT1, microRNA-150-5p (miR-150-5p), and intercellular adhesion molecule-1 (ICAM-1) was determined in ARDS patients and lipopolysaccharide (LPS)-treated human pulmonary microvascular endothelial cells (HPMECs). Next, the interactions among MALAT1, miR-150-5p, and ICAM-1 were explored. Gain- or loss-of-function experiments in HPMECs were employed to determine cell apoptosis and inflammation. Furthermore, a mouse xenograft model of ARDS was established in order to verify the function of MALAT1 in vivo. MALAT1 and ICAM-1 were upregulated, while miR-150-5p was downregulated in both ARDS patients and LPS-treated HPMECs. MALAT1 upregulated ICAM-1 expression by competitively binding to miR-150-5p. MALAT1 silencing or miR-150-5p overexpression was shown to suppress HPMEC apoptosis, decrease the expressions of pro-inflammatory cytokines (IL-6, IL-1ß and TNF-α) and E-selectin in HPMECs, as well as alleviated lung injury in nude mice. These findings demonstrated that MALAT1 silencing can potentially suppress HPMEC apoptosis and alleviate lung injury in ARDS via miR-150-5p-targeted ICAM-1, suggestive of a novel therapeutic target for ARDS.

microRNA-328 in exosomes derived from M2 macrophages exerts a promotive effect on the progression of pulmonary fibrosis via FAM13A in a rat model.

Currently, exosome-enclosed microRNAs (miRs) in exhaled breath have potential for biomarker discovery in patients with pulmonary diseases. This study was performed to investigate the roles of M2 macrophage-derived exosomes expressing miR-328 in pulmonary fibrosis (PF). Microarray-based analysis was used to screen differentially expressed genes (DEGs) and regulatory miRs in PF. The miR-target relationship between FAM13A and miR-328 was confirmed. The expression of FAM13A and miR-328 was measured in PF rats, and gain- and loss-of-function assays were conducted to determine the regulatory effects of FAM13A and miR-328 on PF. In addition, exosomes derived from M2 macrophages were isolated and then cocultured with pulmonary interstitial fibroblasts to identify the role of these exosomes in PF. Furthermore, the effects of M2 macrophage-derived exosomes overexpressing miR-328 on pulmonary fibroblast proliferation and the progression of PF were assessed in vivo. miR-328 might perform a vital function in PF by regulating FAM13A. FAM13A expression was downregulated while miR-328 expression was upregulated in rats with PF, and a miR-target relationship between miR-328 and FAM13A was observed. Additionally, miR-328 overexpression and FAM13A silencing each were suggested to promote pulmonary interstitial fibroblast proliferation and the expression of Collagen 1A, Collagen 3A and α-SMA. Then, in vitro experiments demonstrated that M2 macrophage-derived exosomes overexpressing miR-328 contributed to enhanced pulmonary interstitial fibroblast proliferation and promoted PF. Furthermore, in vivo experiments confirmed the promotive effects of M2 macrophage-derived exosomes overexpressing miR-328 on the progression of PF. Collectively, the results showed that M2 macrophage-derived exosomes overexpressing miR-328 aggravate PF through the regulation of FAM13A.

Emodin enhances cholesterol efflux by activating peroxisome proliferator-activated receptor-γ in oxidized low density lipoprotein-loaded THP1 macrophages.

Peroxisome proliferator-activated receptor (PPAR) γ is a nuclear receptor involved in the regulation of lipid metabolism. In the present study, we sought to investigate the effects of emodin, an anthraquinone derivative isolated from the roots of Rheum palmatum, on PPARγ signalling and cholesterol efflux in macrophage foam cells. Oxidized low-density lipoprotein (oxLDL)-stimulated THP1 macrophages were incubated with different concentrations of emodin (0-10 µmol/L) for 18 h. Western blot analysis and semiquantitative reverse transcription-polymerase chain reaction were used to assess the expression of key genes involved in cholesterol efflux, namely PPARγ, liver X receptor (LXR) α, ATP-binding cassette transporter (ABC) A1 and ABCG1. In addition, apolipoprotein (apo) A-I-mediated cholesterol efflux in emodin-treated cells was measured. Expresssion of PPARγ mRNA and protein was increased in emodin-treated cells in a time- and dose-dependent manner. Emodin treatment also concentration-dependently induced LXRα, ABCA1 and ABCG1 expression. Moreover, emodin promoted apoA-I-mediated cholesterol efflux from oxLDL-loaded THP1 macrophages, which was significantly abolished by pretreatment with the PPARγ-selective antagonist GW9662 or the specific small interfering RNA for PPARγ. Together, the results demonstrate that emodin promotes cholesterol efflux from THP1 macrophages via activation of the PPARγ signalling pathway and may represent a potential anti-atherosclerotic drug.

Prevalence of metabolic syndrome and its relationship with physical activity in suburban Beijing, China.

BACKGROUND: The present study aimed to estimate the up-to-date prevalence of metabolic syndrome and its relationship with physical activity among suburban adults in Beijing, China. METHODS: A cross-sectional survey in a representative sample of 19,003 suburban adults aged 18-76 years was carried out in 2007-2008. Data was collected via questionnaires and blood pressure, anthropometric, and laboratory measurements. RESULTS: Of the residents aged 18-76 years in suburban Beijing, 25.9% (27.3% in men and 25.1% in women), 21.3% (19.4% in men and 22.9% in women), and 25.3% (24.2% in men and 26.1% in women) had 1 component, 2 components, and 3 or more components of metabolic syndrome, respectively. The age-standardized prevalence of metabolic syndrome and its components, including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting plasma glucose, decreased across categories with increasing physical activity. After adjusting for age, sex, education level, smoking, and alcohol consumption, residents were more likely to have metabolic syndrome across categories with decreasing physical activity; a similar relationship also applied to components of metabolic syndrome. CONCLUSION: A high prevalence of metabolic syndrome and its components is commonly present in suburban Beijing. Increasing physical activity can reduce the relative risk of metabolic syndrome and it components.

Correlation of von Willebrand factor gene polymorphism and coronary heart disease.

To characterize von Willebrand factor (vWF) gene polymorphisms at site A1381T and the correlation of plasma vWF levels with coronary heart disease, the vWF genotypes at site A1381T were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients diagnosed with coronary heart disease and normal controls (n=110 per group), and plasma vWF levels were measured by enzyme­linked immunosorbent assay. The results showed that the plasma vWF levels were higher in the experimental group than in the control group and had no association with gender (t=11.69, p<0.05). In the experimental group, the plasma vWF levels were higher in the patients with the AG genotype than in those with the GG genotype (p<0.05). In the control group, the plasma vWF levels of the subjects with blood type O were significantly lower than those of the individuals with other blood types (p<0.05). In the experimental group, all blood types had significantly higher plasma vWF levels than the control group and the difference was significant among different blood types (p<0.05). In summary, vWF gene polymorphisms at site A1381T were not associated with coronary heart disease, but plasma vWF levels were influenced by vWF gene polymorphisms at site A1381T, blood type and coronary heart disease.

Association study of dimethylarginine dimethylaminohydrolase 2 gene polymorphisms and coronary heart disease.

While a number of genetic and environmental risk factors for coronary heart disease (CHD) have been identified, the list of potential risk factors remains long. One candidate is dimethylarginine dimethylaminohydrolase (DDAH2), which is known to be polymorphic in humans. The gene product indirectly increases the endogenous production of nitric oxide, an anti-atherogenic molecule. Therefore, alterations in DDAH2 activity may indirectly result in an increased risk of CHD. We studied allele and genotype distributions for two polymorphic loci of DDAH2, rs805305 and rs2272592, in 180 patients with CHD and 180 healthy controls. Disease history and other clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype at rs805305, and ligase detection reaction (LDR) was used to determine the genotype at rs2272592. Systolic blood pressure and blood triglyceride and glucose levels were higher, and history of hypertension, diabetes, smoking and alcohol use was more common in the patients with CHD (P<0.05). However, the genotype and allele frequencies at the two polymorphic loci of DDAH2 were not statistically different between the two groups. Therefore, no association was observed between the DDAH2 polymorphisms at rs805305 and rs2272592 and CHD.