[17ß-estradiol inhibits interleukin-1ß-induced rat nucleus pulposus cell apoptosis through the PI3K/Akt/mTOR signal pathway].

The apoptosis of nucleus pulposus cells (NPCs) is the main cellular process of intervertebral disc degeneration (IVDD). Our previous studies showed that 17ß-estradiol (E2) protects rat NPCs from interleukin-1ß (IL-1ß)-induced apoptosis via the PI3K/Akt signaling pathway. This study was aimed to investigate whether downstream proteins of PI3K/Akt pathway were involved in inhibition of E2 on NPCs' apoptosis. Primary culture of rat NPCs was isolated by trypsin digestion. Being pretreated with E2 and different inhibitors of downstream proteins of PI3K/Akt pathway, the NPCs were treated with IL-1ß. Cellular apoptosis was detected by Annexin V/PI staining. Cell viability was detected by CCK-8. Cell adhesion was evaluated by cell-collagen binding assay. Phosphorylation levels of mammalian target of Rapamycin (mTOR), glycogen synthase kinase-3ß (GSK-3ß) and nuclear factor κB (NF-κB) were detected by Western blot. The results showed that E2 significantly inhibited the IL-1ß-induced apoptosis of NPCs, reversed the decrease of cell viability and adhesion induced by IL-1ß, and inhibited the down-regulation of mTOR phosphorylation level induced by IL-1ß. Rapamycin could block these protective effects of E2. These results suggest that E2 may inhibit IL-1ß-induced NPCs' apoptosis through the PI3K/Akt/mTOR signaling pathway.

Factors associated with post-traumatic stress disorder of nurses exposed to corona virus disease 2019 in China.

Quantitative studies using validated questionnaires on post-traumatic stress disorder (PTSD) of Nurses exposed to corona virus disease 2019 (COVID-19) in China are rare and the baseline PTSD must first be evaluated before prevention. This study aimed to investigate the factors potentially involved in the level of PTSD of Nurses exposed to COVID-19 in China.In this cross-sectional study, male and female Nurses (n = 202) exposed to COVID-19 from HuBei China were included in the final sample. The PTSD Checklist-Civilian (PCL-C) questionnaire and Simplified Coping Style Questionnaire (SCSQ) were used for evaluation. Multivariate stepwise linear regression analysis and spearman correlation test were performed to assess the association between various factors associated with PTSD.The incidence of PTSD in Nurses exposed to COVID-19 was 16.83%, the PCL-C score was 27.00 (21.00-34.00), and the highest score in the three dimensions was avoidance dimension 9.50 (7.00-13.25); multivariable stepwise linear regression analysis showed that job satisfaction and gender were independently associated with lower PCL-C scores (both P < .001); PCL-C scores were correlated with positive coping (r = -0.151, P = .032), negative coping (r = 0.154, P = .029).Nurses exposed to COVID-19 from HuBei China with job satisfaction, male and positive coping had low PCL-C scores which necessitate reducing the PTSD level by ways of improving job satisfaction, positive response, and strengthening the psychological counseling of female nurses in order to reduce the risk of psychological impairment.

Preoperative SCC-Ag as a predictive marker for the use of adjuvant chemotherapy in cervical squamous cell carcinoma with intermediate-risk factors.

BACKGROUND: For cervical cancer patients whose tumors display a combination of intermediate risk factors, postoperative radiation with or without adjuvant chemotherapy is suggested for them. However, who should be administered with adjuvant chemotherapy is unknown. The current study was designed to explore the clinical value of squamous cell carcinoma antigen (SCC-Ag) in guiding the use of adjuvant chemotherapy in cervical cancer patients. METHODS: A total of 301 cervical cancer patients were included in the present study from March 2006 to March 2016. There were 156 patents who received adjuvant chemotherapy, while the rest of 145 patents did not receive it. The survival analysis including Overall survival (OS) and disease-free survival (DFS) was assessed by using the Kaplan-Meier method. Cox proportional hazards regression was done to detect factors in predicting the tumor prognosis. RESULTS: In patients with high pre-treatment SCC-Ag level, those who received adjuvant chemotherapy acquired better prognosis than patients who did not receive it. Particularly, a lower rate of distant metastasis was found in the group of adjuvant chemo-radiotherapy than that in the group of adjuvant radiotherapy. As for patients with low pre-treatment SCC-Ag level, we observed no differences in both the OS and DFS between patients who were given and not given with adjuvant chemotherapy. In the multivariable analysis, adjuvant chemotherapy was significantly correlated with DFS and distant metastasis-free survival (DMFS) in patients with high SCC-Ag level. CONCLUSION: Preoperative SCC-Ag can be a predictive marker for the use of adjuvant chemotherapy in cervical squamous cell carcinoma with intermediate-risk factors.

17ß­Estradiol protects against interleukin­1ß­induced apoptosis in rat nucleus pulposus cells via the mTOR/caspase­3 pathway.

Intervertebral disc degeneration (IVDD) is the main pathological basis of spinal degenerative diseases, and aberrant apoptosis of nucleus pulposus cells (NPCs) is the main cellular process that causes IVDD. In our previous studies, 17ß­estradiol (E2) was demonstrated to protect rat NPCs from interleukin­1ß (IL­1ß)­induced apoptosis via the PI3K/Akt signaling pathway. However, the downstream signaling pathway of PI3K/Akt is currently unclear. The present study aimed to explore the signaling pathways that are downstream of the PI3K/Akt pathway, including mTOR, NF­κB and glycogen synthase kinase­3ß (GSK­3ß). Annexin V/propidium iodide double staining was used to determine the incidence of apoptosis. Cell Counting kit­8 and MTS assays were used to determine the proliferation and viability of NPCs, respectively. Cellular binding was evaluated using a cell­collagen binding assay. Western blotting was used to determine the protein expression levels of mTOR, NF­κB and GSK­3ß, and their phosphorylation levels, as well as the expression levels of active caspase­3. The results revealed that IL­1ß induced NPC apoptosis and increased the early apoptotic rate of NPCs. However, E2 reduced the early apoptosis of NPCs induced by IL­1ß. In addition, E2 suppressed the decrease in cell viability and binding ability caused by IL­1ß cytotoxicity. Western blotting revealed that E2 also reduced the expression of activated caspase­3, and increased the expression of activated mTOR. As a specific inhibitor of mTOR, rapamycin effectively attenuated the effects of E2. These findings indicated that E2 protected NPCs against apoptosis via activation of the mTOR/caspase­3 pathway.

Systems-Based Interactome Analysis for Hematopoiesis Effect of Angelicae sinensis Radix: Regulated Network of Cell Proliferation towards Hemopoiesis.

OBJECTIVE: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix (ASR) with systems-based interactome analysis. METHODS: This systems-based interactome analysis was designed to enforce the workflow of "ASR (herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments. RESULTS: The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase (SYK), Janus kinase 2 (JAK2), and interleukin-2-inducible T-cell kinase (ITK). The hematopoietic function of ASR was also validated by colony-forming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated. CONCLUSION: This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.

Text Mining of Rheumatoid Arthritis and Diabetes Mellitus to Understand the Mechanisms of Chinese Medicine in Different Diseases with Same Treatment.

OBJECTIVE: To identify the commonalities between rheumatoid arthritis (RA) and diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in different diseases with the same treatment. METHODS: A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention. RESULTS: Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. CONCLUSION: Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.

Corrigendum: Safety Profiles of Tripterygium wilfordii Hook F: A Systematic Review and Meta-Analysis.

[This corrects the article on p. 402 in vol. 7, PMID: 27877128.].

Safety Profiles of Tripterygium wilfordii Hook F: A Systematic Review and Meta-Analysis.

Objective:Tripterygium wilfordii Hook F (TwHF) is a widely used and effective treatment for inflammatory diseases. There have been concerns about its toxicity but no adequate synthesis of the evidence for adverse events (AEs). We aimed to undertake a clinically informative, systematic safety profile of TwHF. Methods: We undertook a systematic review and meta-analysis of experimental studies and observational studies. We searched electronic databases and conference abstracts. Safety outcomes were rates of common AEs. Results: We screened 4137 abstracts for eligibility and included 594 studies in the analysis. The overall incidence of AEs was 26.7% (95% CI 24.8%, 28.8%) in 23,256 TwHF users. The estimates did vary markedly when stratified by specific study types. The incidence of gastrointestinal symptoms, adverse reproductive outcomes, adverse skin reactions, hematologic events and cardiovascular events were 13.3% (95% CI 11.9%, 14.9%), 11.7% (95% CI 10.3%, 13.3%), 7.8% (95% CI 6.3-9.5%), 6.5% (95% CI 5.7-7.4 %) and 4.9% (95% CI 1.6 %, 14.3 %), respectively. The prevalence of irregular menstruation (IM) was increased in patients taking TwHF compared with those given control (odds ratio [OR] 4.65, 95% CI 3.08 to 7.03). TwHF use has lower risk of weight gain (OR 0.12 [95% CI 0.04 to 0.39]) and hair loss (OR 0.37 [95% CI 0.18 to 0.78]). Furthermore, long-term aspirin use (>6 months) has a higher AEs incidence (31.0% [95% CI 24.5%-38.5%]). Conclusion: Our findings suggest that more than one in four patients who were taking TwHF had experienced AEs. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to improve patients' tolerance for TwHF.

[Effect of Combination Therapy of Tetramethylpyrazine with Methotrexate on Inflammatory Reac- tions and Hemorheology in Collagen-induced Arthritis Rats].

OBJECTIVE: To explore the effect of combination therapy of tetramethylpyrazine (TMP) with methotrexate (MTX) on collagen induced arthritis (CIA) rats. METHODS: Totally 55 male SD rats were stratified by body weight. Nine of them were randomly recruited as the normal control group. The rest 46 were immunized with type II bovine collagen (C II) for establishing rheumatoid arthritis (RA) model. Forty successfully modeled rats were randomly divided into 4 groups according to swollen toe degree, i.e., the CIA group, the TMP group, the MTX group, and the TMP plus MTX group, 10 in each group. Rats in the MTX group were administered with MTX (1. 2 mg/kg) , once per week for 4 continuous weeks. Those in the TMP group were administered with 40 mg/kg TMP, once per day for 10 continuous days, and then discontinued for 7 successive days, and continued for another 10 successive days. Rats in the TMP plus MTX group were administered with a mixture of equal dose MTX and TMP, and when MTX was discontinue, TMP was administered according to the way in the TMP group. Equal volume of saline solution was given to rats in the normal control group and the CIA group. Clinical parameters including ankle width (mediolateral diameter) and hindpaw swelling were measured at day 0, 4, 11, 18, and 26 after treatment. Rats were sacrificed 28 days after treatment, their knee joints and ankle joints were collected for pathological analyses. Serum levels of IL-1ß, IL-6, and IL-17A were detected by ELISA. Changes of fibrinogen (FIB) and platelet aggregation rate (PAg) were detected. RESULTS: Compared with the normal control group, the ankle width and hindpaw swelling increased significantly (P < 0.01), contents of FIB and PAg increased obviously (P < 0.05, P < 0.01), serum levels of IL-1ß, IL-6, and IL-17 increased remarkably (P <0. 01) in the CIA group. Obvious cell proliferation, inflammatory cell infiltration, hyperemia and edema of synovial tissues could be seen. Pannus formed and immerged in cartilages, resulting in necrosis. Compared with the model group, changes of ankle width and hindpaw swelling were all alleviated in each medicated group (P <0. 05, P <0. 01). Of them, the effect was superior in the MTX group to that of the TMP group and the MTX plus TMP group (P < 0.05, P < 0.01). Contents of FIB, serum levels of IL-1ß and IL-6 decreased significantly in the MTX group (P < 0.05). Contents of FIB, serum levels of IL-1ß and IL-6 decreased significantly in the TMP group and the MTX plus TMP group (P < 0.05). Besides, serum levels of FIB and IL-6 were obviously lower in the MTX plus TMP group than in the TMP group and the MTX group (P < 0.01). Levels of PAg and IL-17A were more significantly lowered in the TMP group than in the MTX plus TMP group and the MTX group. Pathological changes could be alleviated in each medicated group, with the optimal effect obtained in the MTX plus TMP group. CONCLUSION: Combination of TMP with MTX could significantly ameliorate inflammatory reactions and FIB contents of CIA rats.

[Exploring the association rules of clinical application of shenmai injection through text mining].

OBJECTIVE: To explore the rules of clinical application of Shenmai Injection (SI). METHODS: The data sets of SI were downloaded from CBM database by the method of literature retrieved from Jan. 1980 to May 2012. Rules of Chinese medical patterns, diseases, symptoms, Chinese patent medicines (CPM), and Western medicine (WM) were mined out by data slicing algorithm, and they were demonstrated in frequency tables and two-dimension based network. RESULTS: Totally 3 159 literature were recruited. Results showed that SI was most frequently correlated with stasis syndrome and deficiency syndrome. Heart failure, arrhythmia, myocarditis, myocardial infarction, and shock were core diseases treated by SI. Symptoms such as angina pectoris, fatigue, chest tightness/pain were mainly relieved by SI. For CPM, SI was most commonly used with Compound Danshen Injection, Astragalus Injection, and so on. As for WM, SI was most commonly used with nitroglycerin, fructose, captopril, and so on. CONCLUSIONS: The syndrome types and mining results of SI were the same with its instructions. Stasis syndrome was the potential Chinese medical pattern of SI. Heart failure, arrhythmia, and myocardial infarction were potential diseases treated by SI. For CPM, SI was most commonly used with Danshen Injection, Compound Danshen Injection, and so on. And for WM, SI was most commonly used with nitroglycerin, fructose, captopril, and so on.

Apoptin sensitizes radiation-induced cell death via classic mitochondrial, caspase and p53-dependent signaling in HepG2 cells.

Resistance or insensitivity to radiation therapy is one of the hallmarks of hepatocellular carcinoma. Sensitizing radioresistant cancer by combining radiation with other therapeutics to induce apoptosis has been widely investigated. Our previous study showed that chicken anaemia virus-derived apoptin protein induced the apoptosis of hepatic carcinoma HepG2 cells. In the present study, we demonstrated that apoptin sensitizes cells to radiation-induced apoptosis using a lentivirus-apoptin expression system in hepatic carcinoma HepG2 cells. Combination therapy with radiation and apoptin dramatically induced mitochondrial cytochrome c release and the cleavage of caspases -9, -3 and -7. Our findings are also the first to show that the combination of radiation and apoptin up-regulates p53 expression. Thus, apoptin treatment represents a potential method for enhancing the effectiveness of radiotherapy in poorly responding hepatocellular carcinoma.

CDK5 regulates cell adhesion and migration in corneal epithelial cells.

CDK5 and its activator, p35, are expressed in mouse corneal epithelium and can be coimmunoprecipited from corneal epithelial cell lysates. Immunostaining shows CDK5 and p35 in all layers of the corneal epithelium, especially along the basal side of the basal cells. Stable transfection of corneal epithelial cells with CDK5, which increases CDK5 kinase activity by approximately 33%, also increases the number of cells adhering to fibronectin and the strength of adhesion. CDK5 kinase activity seems to be required for this effect, because the kinase inactive mutation, CDK5-T33, either reduces adhesion or has no significant effect, depending on the level of expression. Using an in vitro scrape wound in confluent cultures of stably transfected cells to examine the effect of CDK5 on cell migration, we show that reoccupation of the wound area is significantly decreased by CDK5 and increased by CDK5-T33. These findings indicate that CDK5 may be an important regulator of adhesion and migration of corneal epithelial cells.