This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
Animals ; Humans ; Male ; Mice ; Rats ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Phosphodiesterase 5 Inhibitors ; Plasminogen Activator Inhibitor 1

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl

Objective: Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM Methods: EVs were isolated from the serum of healthy subjects, quantified Results: PM Conclusions EVs treatment promotes cell survival and attenuates PM
A549 Cells ; Air Pollutants/toxicity* ; Apoptosis/drug effects* ; Cell Survival/drug effects* ; Extracellular Vesicles ; Humans ; Male ; Middle Aged ; Particulate Matter/toxicity* ; Protective Agents/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Serum

According to the latest research progress at home and abroad, and the domestic situation, China Diabetic Cellular and Interventional Therapy Technology Alliance forDiabetic Foot developed and issued the fifth edition of clinical guidelines for comprehensive interventional diagnosis and treatment of diabetic foot, which covers domestic evidence,references foreign evidence, and reflects the progress in China. The interpretation focuses on the updated key points.

In recent years, the safety problems and events of traditional Chinese medicine represented by liver injury have occurred frequently. In particular, Polygonum multiflorum has been widely used and considered as a "non-toxic" tonic traditional Chinese medicine for thousands of years. However, in recent years, frequent reports of liver injury events have attracted widespread attention at home and abroad, which has made unfavorable impacts on traditional Chinese medicine and its international development. Some scho-lars have found that susceptible genes of P. multiflorum on liver injury lay a scientific foundation for formulating rational comprehensive prevention and control measures for liver injury risk of P. multiflorum and its relevant preparations. But what are the risk signals of adverse reactions of P. multiflorum in clinical application? Spontaneous reporting system is an important way to monitor and find adverse drug reaction(ADR) signals after the drug is launched in the market. It can find the ADR signals in time and effectively, and then effectively prevent and avoid the occurrence of adverse drug events. At present, the data mining technique has gradually become the main method of ADR/adverse event(AE) report analysis and evaluation at home and abroad. Specifically, Bayesian confidence propagation neural network in Bayesian method is a commonly used risk signal early warning analysis method. In this paper, BCPNN method was used to excavate the risk signals of adverse reactions of Xinyuan Capsules, a traditional Chinese medicine preparation containing P. multiflorum, such as nausea, diarrhea, rash, dizziness, vomiting, abdominal pain, headache, liver cell damage, so as to provide evidence-based evidence for clinical safe and rational use of drugs.
Adverse Drug Reaction Reporting Systems ; Bayes Theorem ; Capsules ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Neural Networks, Computer

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5

【Objective】 To explore the regulatory mechanism of miR-204-3p targeting EphB2 gene on proliferation, apoptosis and invasion of NSCLC. 【Methods】 A549 cells were cultured and divided into 5 groups: NC mimic group, miR-204-3p mimic group, OE NCgroup, OE EphB2 group, miR-204-3p mimic+ OE EphB2 group. MTT, flow cytometry, Transwell and scratch test were used to detect cell proliferation, cycle, apoptosis, invasion and migration. Double Luciferase Report was used to analyze the targeting relationship between mir-204-3p and EphB2. The mRNA and protein expression of miR-204-3p, EphB2 were detected by qPCR and WB. 【Results】 Innon-small lung cancer cells, the binding site of mir-204-3p and EphB2 3'UTR region, the high expression of miR-204-3p significantly inhibited the expression of EphB2 mRNA and protein(P<0.01). Compared with the Negtively control group(NC mimic group), the proliferation of A549 cells in miR-204-3p mimicgroup were significantly decrease(P<0.05), and the apototic rate was significantly increased(P<0.05). Also, the cell migration and invasion ability were also decreased significantly(P<0.05). Transfection of Ephb2 reversed the above changes. In addition, in non-small cell lung cancer tissues, miR-204-3p was negatively correlated with EphB2 expression(r=0.636, P<0.001), and the overall survival was shorter in EphB2 high expression groups than that in low expression groups(logrank χ²=3.899, P=0.049) . 【Conclusion】 MiR- 204- 3p inhibits proliferation, migration and invasion of non-small lung cancer cells and induces apoptosis by down-regulating EphB2.

OBJECTIVE: To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy. METHODS: Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms. RESULTS: (1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline. CONCLUSION Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.
Carcinoma, Hepatocellular ; Graft vs Host Disease ; Humans ; Killer Cells, Natural ; Leukocytes, Mononuclear ; Liver Neoplasms

Objective To investigate the cytotoxic effect mechanism of the unsaturated fatty acids on human cervical carcinoma of ME-180 cells.Methods The 2 × 108 cell · L-1 ME-180 cells were moved into the 96 hole culture plate,per hole 90 μL.Three concentrations of the drug groups:0.3,0.6,0.9 mg· L-1 unsaturated fatty acid (prepared with DMSO) per hole 90 μL.The 5-fluorouracil(5-FU) group:10mg · L-1 5-FU (prepared with phosphate buffer) per hole 10 μL.Control group:30 μL · L-1 DMSO per hole 10 μL.Each group set of four repeat hole,in saturated humidity condition of 37 ℃ and 5％ CO2 in 48 h.The inhibition rate and apoptosis rate of unsaturated fatty acids were detected with a trypan blue,thiazole blue (MTT),and flow cytometry method.Results When ME-180 cells were administered with the unsaturated fatty acids at the doses of 0.3,0.6,0.9 mg · L-1 for 48 h,ME -180 living cell count with the increase of drug concentration and action time is reduced.The cells proliferation inhibition rate were 43.35％,51.75％,66.45％ in three concentrations of the drug groups;apoptosis rate were 18.21％,23.11％,28.06％ in the three groups,respectively.Compared with the drug groups and the control group on the number of living cells,inhibition rate and apoptosis rate,the differences were statistically significant (P ＜0.01).Conclusion The unsaturated fatty acids has significant toxic effects on ME-180 cells.The toxic effect mechanism of the unsaturated fatty acids is related to inhibite proliferation on cell and induce-cell apoptosis.