Protective effects of leonurine hydrochloride on pyroptosis in premature ovarian insufficiency via regulating NLRP3/GSDMD pathway.

BACKGROUND: Premature ovarian insufficiency is common in clinically infertile patients. The NOD-like receptor family pyrin domain-containing 3 (NLRP3)/Gasdermin D (GSDMD) signaling pathway plays a key role in premature ovarian insufficiency. Leonurine (Leo) is one of the important active ingredients extracted from Leonurus japonicus Houttuyn, which can inhibit NLRP3 activation. However, whether leonurine hydrochloride plays a protective role in premature ovarian insufficiency through actions on NLRP3/GSDMD signaling is not yet known. METHODS: After cyclophosphamide-induced premature ovarian insufficiency was established in female mice, Leo was injected intraperitoneally over four weeks to evaluate the ovarian function and anti-pyroptosis effects using the metrics of fertility, serum hormone level, ovary weight, follicle number, expression of NLRP3/GSDMD pathway-related proteins, and serum IL-18 and IL-1ß levels. RESULTS: Intraperitoneal administration of leonurine hydrochloride was found to significantly protect fertility and maintain both serum hormone levels and follicle number in mice with premature ovarian insufficiency. Mice treated with leonurine hydrochloride consistently resisted cyclophosphamide-induced ovarian damage by inhibiting the activation of NLRP3 inflammasome, Caspase-1 and GSDMD in both ovarian tissue and granulosa cells, which led to lower levels of IL-18 and IL-1ß in the serum (p < 0.05, p < 0.01, p < 0.001). CONCLUSION: Intraperitoneal administration of leonurine hydrochloride prevents cyclophosphamide-induced premature ovarian insufficiency in mice by inhibiting NLRP3/GSDMD-mediated pyroptosis.

Fentanyl enhances HIV infection in vitro.

Acquired immunodeficiency syndrome (AIDS) caused by Human immunodeficiency virus type 1 (HIV-1) has a high tendency among illicit drug abusers. Recently, it is reported that abuse of fentanyl, a potent synthetic µ receptor-stimulating opioid, is an independent risk factor for HIV-1 infection. However, the mechanism of action in augmenting HIV-1 infection still remains elusive. In this study, we found that fentanyl enhanced infection of HIV-1 in MT2 cells, primary macrophages and Jurkat C11 cells. Fentanyl up-regulated CXCR4 and CCR5 receptor expression, which facilitated the entry of virion into host cells. In addition, it down-regulated interferon-ß (IFN-ß) and interferon-stimulated genes (APOBEC3F, APOBEC3G and MxB) expression in MT2 cells. Our findings identify an essential role of fentanyl in the positive regulation of HIV-1 infection via the upregulation of co-receptors (CXCR4/CCR5) and downregulation of IFN-ß and ISGs, and it may have an important role in HIV-1 immunopathogenesis.

A new scoring system to evaluate adjuvant chemotherapy for patients with T2N0M0 gastric cancer after D2 gastrectomy.

BACKGROUND: At present, there is insufficient medical evidence to determine whether adjuvant chemotherapy is necessary for T2N0M0 gastric cancer. AIM: To obtain a risk score to assess the need for adjuvant chemotherapy in patients with T2N0M0 gastric cancer. METHODS: We identified 325 patients with pathological T2N0M0 stage primary gastric cancer at the National Cancer Center between 2011 and 2018. Univariate and multivariate Cox regression analyses were performed to predict factors affecting prognosis. Vascular invasion, tumor site, and body mass index were assessed, and a scoring system was established. We compared the survival outcomes and benefits of adjuvant chemotherapy between the different subgroups. RESULTS: Five-year survival rates of the score 0, 1, 2, and 3 groups were 92%, 95%, 80%, and 50%, respectively (P < 0.001). In the score 2-3 group, five-year survival rates for patients in the adjuvant chemotherapy group and postoperative observation group were 95% and 61%, respectively (P = 0.021). CONCLUSION: For patients with T2N0M0 stage gastric cancer and two or more risk factors, adjuvant chemotherapy after D2 gastrectomy may have a survival benefit.

Adjuvant chemoradiotherapy vs adjuvant chemotherapy in locally advanced Siewert type II/III adenocarcinoma of gastroesophageal junction after D2/R0 resection.

BACKGROUND: For Siewert type II/III adenocarcinoma of gastroesophageal junction (AGE), the efficacy of adjuvant chemoradiotherapy (CRT) after D2/R0 resection remains uncertain. AIM: To determine whether CRT was superior to chemotherapy (CT) alone after D2/R0 resection for locally advanced Siewert type II/III AGE. METHODS: We identified 316 locally advanced Siewert type II/III AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018. 57 patients received adjuvant CRT and 259 patients received adjuvant CT. We followed patients for overall survival (OS), relapse-free survival, and recurrence pattern. RESULTS: Five-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9% (P = 0.010). Five-year OS rates of the CRT group and the CT group for Siewert type III AGE patients were 65.7% and 43.9% (P = 0.006). Among the 195 patients whose recurrence information could be obtained, 18 cases (34.6%) and 61 cases (42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively. The local and regional recurrence rates in the CRT group were lower than that in the CT group (22.2% vs 24.6%, 27.8% vs 39.3%). Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type III AGE. CONCLUSION: For locally advanced Siewert type III AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.

[Evolution Characteristics and Clinical Significance of Blood Separation in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the evolution of blood separation results by gel extraction of multiple myeloma (MM) patients, and to evaluate the clinical value of abnormal blood separation results for the evaluation of disease and prognosis. METHODS: The clinical data of 5 patients diagnosed newly MM patients with abnormal blood separation of gel collection vessels in our hospital were retrospectively analyzed, and the changes of blood separation results and blood index levels were followed up with the improvement of treatment effect, and the correlation of different blood index levels was analyzed. RESULTS: In 5 patients with newly diagnosed MM, the blood separation result showed floating phenomenon after centrifugation, which divided into three layers and the order from top to bottom is separator gel, serum, and red blood cells(RBC). With partial remission of clinical symptoms, the blood separation results were still abnormal, which were divided into three layers from top to bottom: serum, RBC and separator gel. Finally, with complete remission of the disease, blood separation results returned to normal, from top to bottom: serum, separator gel, RBC. With the blood separation results from abnormal to normal, the blood routine indicators: Hb, Hct levels gradually increased, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) gradually decreased; biochemical indexes: TP, GLB, Ig and ß2-MG levels gradually decreased. Tumor load related indicators: serum IL-6, TNF-α, IL-17 levels gradually decreased, and IL-35 levels gradually increased; and the differences were statistically significant (P<0.05). Pearson correlation analysis showed that serum ß2-MG was positively correlated with IL-6, TNF-α and IL-17 levels (r=0.710, 0.756, 0.581, P<0.05), and negatively correlated with IL-35 level (r=-0565, P<0.05). CONCLUSION: Abnormal blood separation exists in MM patients, and there are significant differences in blood, tumor load and immune balance related indexes in patients with different blood separation results, which provides partial experimental basis for evaluation of disease, efficacy and prognosis with different blood separation results.

Can Gastric Cancer Patients with High Mandard Score Benefit from Neoadjuvant Chemotherapy?

A high Mandard score may indicate the tumor is insensitive to chemotherapy. We analyzed tumor regression and lymph node response under different Mandard scores to assess the impact of Mandard score on prognosis. Methods. Mandard scores and ypN stage of postoperative pathological reports were recorded. The results were reviewed by a professional pathologist. The radiologist compared the tumor regression before and after chemotherapy by computed tomography (CT). The survival of all patients was obtained by telephone follow-up. Multivariate Cox regression was used to assess the relationship between overall risk of death and Mandard score, imaging evaluation, and ypN stage. Results. In the Mandard score (4-5) group, the median survival time for PR and ypN0 patients was 68.5 and 76.7 months. While in the Mandard score (1-2) group, the median survival time for PD and ypN3a patients was 15.6 and 14.5 months. Imaging evaluation of tumor regression (PR 68.5 months, SD 27.8 months, and PD 10.2 months) and lymph node remission (ypN0 76.7 months, ypN1 61.6 months, ypN2 18.0 months, ypN3a 18.7 months, and ypN3b 18.3 months) showed improved survival. Mandard score, imaging evaluation, and ypN stage are important prognostic factors affecting prognosis. Conclusion. A high Mandard score does not mean neoadjuvant chemotherapy is ineffective in gastric cancer. Patients with imaging evaluation of tumor regression and ypN stage reduction may benefit from neoadjuvant chemotherapy.

Laparoscopic vs open total gastrectomy for advanced gastric cancer following neoadjuvant therapy: A propensity score matching analysis.

BACKGROUND: Laparoscopic total gastrectomy (LTG) has drawn increasing attention over the years. Although LTG has shown surgical benefits compared to open TG (OTG) in early stage gastric cancer (GC), little is known about the surgical and oncological outcomes of LTG for advanced GC following neoadjuvant therapy (NAT). AIM: To compare the long- and short-term outcomes of advanced GC patients who underwent LTG vs OTG following NAT. METHODS: Advanced GC patients who underwent TG following NAT between April 2011 and May 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences were enrolled and stratified into two groups: LTG and OTG. Propensity score matching analysis was performed at a 1:1 ratio to overcome possible bias. RESULTS: In total, 185 patients were enrolled (LTG: 78; OTG: 109). Of these, 138 were paired after propensity score matching. After adjustment for propensity score matching, baseline parameters were similar between the two groups. Compared to OTG, LTG was associated with a significantly shorter length of hospital stay (P = 0.012). The rates of R0 resection, lymph node harvest, and postoperative morbidity did not significantly differ between the two groups. Overall survival (OS) outcomes were comparable between the two groups. Pathological T and N stages were found to be independent risk factors for OS. CONCLUSION: LTG can be a feasible method for advanced GC patients following NAT, as it appears to be associated with better short- and comparable long-term outcomes compared to OTG.

Establishment and evaluation of a BALBc mouse model of Burkholderia pseudomallei via nasal infection / 中国热带医学

@#Abstract: Objective To establish an animal model of BALB/c mice infected with Burkholderia pseudomallei through the nose (inhalation route), provides a reliable animal model for the follow-up studies on the virulence of melioidosis and the pathogenesis of acute melioidosis. Methods　The experiment was carried out through infecting with Burkholderia pseudomallei through the nose (inhalation route). The pathophysiological response, visceral pathological damage and bacterial colonization of the mice infected with Burkholderia pseudomallei were observed by gross anatomy, histopathology and tissue homogenate count, and the biological characteristics of the mouse model of acute melioidosis were analyzed accordingly. Then we compared the physiological responses in BALB/c mice between the Burkholderia pseudomallei and non-pathogenic Burkholderia thailandensis. Results　In the model of acute nasal infection with Burkholderia thailandensis, most death happened between the 3rd to 5th day after infection, 3×105-3×106 CFU was the suitable dose for acute fatal melioidosis model of BALB/c mice, and the medium lethal dose was about 3×104-3×105 CFU. Both gross anatomy and tissue HE staining showed that abscesses or necrosis were found in the lung, spleen and liver, especially in the spleen and lung, which was positively correlated with the challenge dose. Viable bacteria was isolated from the blood, lung, spleen and liver of Burkholderia pseudomallei-infected mice, and the bacteria account colonization was related to tissue specificity. The concentration of live bacteria isolated from in the blood was the highest [Log2 value: (10.28±0.34) CFU/mL], and the organ with the maximum quantity of bacteria was the lung [Log2 value: (7.54±2.11) CFU/total organ]. It has been reported that the biological effects of Burkholderia pseudomallei and its homologous non-pathogenic Burkholderia thailandensis were similar at the cellular level, like multi-nuclear giant cell formation and active intracellular replication, while it is still unclarrified in the differences of virulence in mice. In this study, it was proved that Burkholderia thailandensis was not fatal to mice even at a high dose (8×107CFU), or detected from mice infected with it via nasal. Conclusion　We successfully established a reliable BALB/c mouse model (acute lethal model) of melioidosis via nasal infection, described its biological characteristics, and identified the different biological responses between Burkholderia pseudomallei and its homologous non-pathogenic Burkholderia thailandensis in mice.

Retrospective analysis of surgically treated pT4b gastric cancer with pancreatic head invasion.

BACKGROUND: For advanced gastric cancer patients with pancreatic head invasion, some studies have suggested that extended multiorgan resections (EMR) improves survival. However, other reports have shown high rates of morbidity and mortality after EMR. EMR for T4b gastric cancer remains controversial. AIM: To evaluate the surgical approach for pT4b gastric cancer with pancreatic head invasion. METHODS: A total of 144 consecutive patients with gastric cancer with pancreatic head invasion were surgically treated between 2006 and 2016 at the China National Cancer Center. Gastric cancer was confirmed in 76 patients by postoperative pathology and retrospectively analyzed. The patients were divided into the gastrectomy plus en bloc pancreaticoduodenectomy group (GP group) and gastrectomy alone group (GA group) by comparing the clinicopathological features, surgical outcomes, and prognostic factors of these patients. RESULTS: There were 24 patients (16.8%) in the GP group who had significantly larger lesions (P < 0.001), a higher incidence of advanced N stage (P = 0.030), and less neoadjuvant chemotherapy (P < 0.001) than the GA group had. Postoperative morbidity (33.3% vs 15.3%, P = 0.128) and mortality (4.2% vs 4.8%, P = 1.000) were not significantly different in the GP and GA groups. The overall 3-year survival rate of the patients in the GP group was significantly longer than that in the GA group (47.6%, median 30.3 mo vs 20.4%, median 22.8 mo, P = 0.010). Multivariate analysis identified neoadjuvant chemotherapy [hazard ratio (HR) 0.290, 95% confidence interval (CI): 0.103-0.821, P = 0.020], linitis plastic (HR 2.614, 95% CI: 1.024-6.675, P = 0.033), surgical margin (HR 0.274, 95% CI: 0.102-0.738, P = 0.010), N stage (HR 3.489, 95% CI: 1.334-9.120, P = 0.011), and postoperative chemoradiotherapy (HR 0.369, 95% CI: 0.163-0.836, P = 0.017) as independent predictors of survival in patients with pT4b gastric cancer and pancreatic head invasion. CONCLUSION: Curative resection of the invaded pancreas should be performed to improve survival in selected patients. Invasion of the pancreatic head is not a contraindication for surgery.

Low body mass index is an independent predictor of poor long-term prognosis among patients with resectable gastric cancer.

BACKGROUND: The association between body mass index (BMI) and clinical outcomes remains unclear among patients with resectable gastric cancer. AIM: To investigate the relationship between BMI and long-term survival of gastric cancer patients. METHODS: This retrospective study included 2526 patients who underwent radical gastrectomy for gastric cancer between September 2013 and June 2018. The patients were divided into four groups: Group A (low BMI, < 18.5 kg/m2), group B (normal BMI, 18.5-24.9 kg/m2), group C (overweight, 25-29.9 kg/m2), and group D (obese, ≥ 30 kg/m2). Clinicopathological findings and survival outcomes were recorded and analyzed. RESULTS: Preoperative weight loss was more common in the low-BMI group, while diabetes was more common in the obese group. Upper-third gastric cancer accounted for a large proportion of cases in the higher BMI groups. Major perioperative complications tended to increase with BMI. The 5-year overall survival rates were 66.4% for group A, 75.0% for group B, 77.1% for group C, and 78.6% for group D. The 5-year overall survival rate was significantly lower in group A than in group C (P = 0.008) or group D (P = 0.031). Relative to a normal BMI value, a BMI of < 18.5 kg/m2 was associated with poor survival (hazard ratio: 1.558, 95% confidence interval: 1.125-2.158, P = 0.008). CONCLUSION: Low BMI, but not high BMI, independently predicted poor survival in patients with resectable gastric cancer.

Treatment strategies for gastric cancer during the COVID-19 pandemic.

The coronavirus disease 2019 pandemic has become a major global public health problem. Governments are taking the necessary steps to reduce the movement of people to contain the spread of the virus. However, these measures have caused considerable distress to patients with gastric cancer who are newly diagnosed or are undergoing treatment. In addition to the cancer, they must deal with longer waiting times for surgery and poor communication with doctors. Furthermore, gastric cancer patients generally have low immunity and a poor nutritional status, so they are a high-risk group for infection with the novel coronavirus. Therefore, it is necessary to formulate reasonable outpatient management strategies to reduce the adverse effects of the pandemic on their treatment. We summarize the management strategies for patients with gastric cancer during the pandemic.

Treatment of afferent loop syndrome using fluoroscopic-guided nasointestinal tube placement: Two case reports.

BACKGROUND: Afferent loop syndrome (ALS) is a rare mechanical complication that occurs after reconstruction of the stomach or esophagus to the jejunum, such as Billroth II gastrojejunostomy, Roux-en-Y gastrojejunostomy, or Roux-en-Y esophagoje-junostomy. Traditionally, an operation is the first choice for benign causes. However, for patients in poor physical condition who experience ALS soon after R0 resection, the type of treatment remains controversial. Here, we present an efficient conservative method to treat ALS. CASE SUMMARY: Case 1 was a 69-year-old male patient who underwent total gastrectomy with Roux-en-Y jejunojejunostomy. On postoperative day (POD) 10 he developed symptoms of ALS that persisted and increased over 1 wk. Case 2 was a 59-year-old male patient who underwent distal gastrectomy with Billroth II gastrojejunostomy. On postoperative day POD 9 he developed symptoms of ALS that persisted for 2 wk. Both patients underwent fluoroscopic-guided nasointestinal tube placement with maintenance of continuous negative pressure suction. Approximately 20 d after the procedure, both patients had recovered well and were discharged from hospital after removal of the tube. At 3-mo follow-up, there were no signs of ALS in these two patients. CONCLUSION: This is the first report of treating postoperative ALS by fluoroscopic-guided nasointestinal tube placement. Our cases demonstrate that this procedure is an effective and safe method to treat ALS that relieves patients' symptoms and avoids complications caused by other invasive procedures.

HTNV Sensitizes Host Toward TRAIL-Mediated Apoptosis-A Pivotal Anti-hantaviral Role of TRAIL.

Hantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and have led to public health threat in China. The pathogenesis of HFRS is complex and involves capillary leakage due to the infection of vascular endothelial cells. Accumulating evidence has demonstrated that hantavirus can induce apoptosis in many cells, but the mechanism remains unclear. Our studies showed that Hantaan virus (HTNV) infection could induce TNF-related apoptosis-inducing ligand (TRAIL) expression in primary human umbilical vein endothelial cells (HUVECs) and sensitize host cells toward TRAIL-mediated apoptosis. Furthermore, TRAIL interference could inhibit apoptosis and enhance the production of HTNV as well as reduce IFN-ß production, while exogenous TRAIL treatment showed reverse outcome: enhanced apoptosis and IFN-ß production as well as a lower level of viral replication. We also observed that nucleocapsid protein (NP) and glycoprotein (GP) of HTNV could promote the transcriptions of TRAIL and its receptors. Thus, TRAIL was upregulated by HTNV infection and then exhibited significant antiviral activities in vitro, and it was further confirmed in the HTNV-infected suckling mice model that TRAIL treatment significantly reduced viral load, alleviated virus-induced tissue lesions, increased apoptotic cells, and decreased the mortality. In conclusion, these results demonstrate that TRAIL-dependent apoptosis and IFN-ß production could suppress HTNV replication and TRAIL treatment might be a novel therapeutic target for HTNV infection.

Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages.

Opioid abuse alters the functions of immune cells in both in vitro and in vivo systems, including macrophages. Here, we investigated the effects of methadone, a widely used opioid receptor agonist for treatment of opiate addiction, on the expression of intracellular viral restriction factors and HIV replication in primary human macrophages. We showed that methadone enhanced the HIV infectivity in primary human macrophages. Mechanistically, methadone treatment of macrophages reduced the expression of interferons (IFN-ß and IFN-λ2) and the IFN-stimulated anti-HIV genes (APOBEC3F/G and MxB). In addition, methadone-treated macrophages showed lower levels of several anti-HIV microRNAs (miRNA-28, miR-125b, miR-150, and miR-155) compared to untreated cells. Exogenous IFN-ß treatment restored the methadone-induced reduction in the expression of the above genes. These effects of methadone on HIV and the antiviral factors were antagonized by pretreatment of cells with naltrexone. These findings provide additional evidence to support further studies on the role of opiates, including methadone, in the immunopathogenesis of HIV disease.

Novel secondary metabolites from the endobryophytic fungus Botrysphaeria laricina and their biological activity.

One novel polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid metabolite, laricinin A (1), two new meroterpenoids, tricycloalternarenes X and Y (2 and 3), one new coumarin, 3,4,7-trihydroxy-6-methylcoumarin (4), together with the known ethyl acetylorsellinate (5), diorcinol K (6), and tricycloalternarenes C and D (7 and 8) were obtained from culture of the fungus Botrysphaeria laricina isolated from the moss Rhodobryum umgiganteum. The structures of the new compounds were elucidated based on extensive spectroscopic techniques including HRMS and 1D and 2D NMR measurements. The absolute configuration of compound 1 was determined by ECD calculation and it was the first example of a novel group of PKS-NRPS hybrids possessing an unprecedented methyldihydropyran-isobutylpyrrolidinone skeleton. Compounds 2, 7, and 8 showed significant quinone reductase inducing activity in Hepa 1c1c7 cells.

Three new triterpenoids from Mallotus macrostachyus.

Three new triterpenoids, mallomacrostins A-C (1-3), and 11 known ones (4-14) were obtained from the twigs and leaves of Mallotus macrostachyus. Mallomacrostin A possessed a new trinor-D:B-friedobaccharane skeleton. The structures of the new compounds were elucidated on the basis of extensive spectroscopic techniques including HR-ESIMS and NMR and the structure of 1 was confirmed by single crystal X-ray diffraction analysis. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 2 and 10 exhibited significant anti-inflammatory activity by inhibiting LPS-induced release of nitric oxide with IC50 of 70.0 µM and 14.0 µM, respectively.

Selection of glucocorticoid-sensitive patients in interstitial lung disease secondary to connective tissue diseases population by radiomics.

PURPOSE: The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. METHODS: A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. RESULTS: Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%-60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. CONCLUSION: Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy.

Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease.

BACKGROUND/AIMS: Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown. METHODS: Genome-wide circRNA expression profiling was performed to identify pterygium -related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was performed to predict the function of differentially expressed circRNAs in pterygium. MTT assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI staining were performed to determine the effect of circRNA silencing on pterygium fibroblast and epithelial cell function. RESULTS: Approximately 669 circRNAs were identified to be abnormally expressed in pterygium tissues. GO analysis demonstrated that the host genes of differentially expressed circRNAs were targeted to extracellular matrix organization (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis showed that dysregulated circRNAs-mediated regulatory networks were mostly enriched in focal adhesion signaling pathway. Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability, proliferation, migration, and apoptosis of pterygium fibroblast and epithelial cells in vitro. CONCLUSIONS: This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium.

Long non-coding RNA MEG3 silencing protects against light-induced retinal degeneration.

Excessive light exposure leads to retinal degeneration and accelerates the progression and severity of several ocular diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa. Long non-coding RNAs (LncRNAs) have emerged as important regulators of photoreceptor development and ocular diseases. In this study, we investigated the role of lncRNA-MEG3 in light-induced retinal degeneration. MEG3 expression was significantly up-regulated after light insult in vivo and in vitro. MEG3 silencing protected against light-induced retinal degeneration in vivo and light-induced photoreceptor cell apoptosis in vitro. Mechanistically, MEG3 regulated retinal photoreceptor cell function by acting as p53 decoy. MEG3 silencing decreased caspase 3/7 activity, up-regulated anti-apoptotic protein (Bcl-2) expression, and down-regulated pro-apoptotic protein (Bax) expression. Taken together, this study provides a promising method of MEG3 silencing for treating light-induced retinal degeneration.

Significant elevation of serum caspase-3 levels in patients with intracerebral hemorrhage.

BACKGROUND: Caspase-3 is a potential marker of apoptosis. We investigated whether serum caspase-3 concentrations were increased and its association with severity and prognosis after intracerebral hemorrhage (ICH). METHODS: This prospective clinical study recruited 112 ICH patients and 112 healthy individuals. Serum was assayed for caspase-3 using enzyme-linked immunosorbent assay. Stroke severity was quantified by National Institute of Health Stroke Scale (NIHSS) and hematoma volume. Six-month outcome was measured by modified Rankin Scale. Analyses were performed using univariate and multivariate analyses. RESULTS: Patients had significantly higher serum caspase-3 concentrations than controls. Capase-3 concentrations correlated with NIHSS score and hematoma volume. Serum caspase-3 emerged as an independent predictor for 6-month mortality and bad prognosis (modified Rankin scale score>2). Based on receiver operating characteristic curve, caspase-3 concentrations showed similar prognostic value when compared with NIHSS score and hematoma volume. CONCLUSION: Serum caspase-3 concentrations are increased in ICH patients as well as correlate with clinical severity and prognosis.