[Research progress in preparations of Panax ginseng].

Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling.

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.

High-Efficiency 3D DNA Walker Immobilized by a DNA Tetrahedral Nanostructure for Fast and Ultrasensitive Electrochemical Detection of MiRNA.

Herein, by directly limiting the reaction space, an ingenious three-dimensional (3D) DNA walker (IDW) with high walking efficiency is developed for rapid and sensitive detection of miRNA. Compared with the traditional DNA walker, the IDW immobilized by the DNA tetrahedral nanostructure (DTN) brings stronger kinetic and thermodynamic favorability resulting from its improved local concentration and space confinement effect, accompanied by a quite faster reaction speed and much better walking efficiency. Once traces of target miRNA-21 react with the prelocked IDW, the IDW could be largely activated and walk on the interface of the electrode to trigger the cleavage of H2 with the assistance of Mg2+, resulting in the release of amounts of methylene blue (MB) labeled on H2 from the electrode surface and the obvious decrease of the electrode signal. Impressively, the IDW reveals a conversion efficiency as high as 9.33 × 108 in 30 min with a much fast reaction speed, which is at least five times beyond that of typical DNA walkers. Therefore, the IDW could address the inherent challenges of the traditional DNA walker easily: slow walking speed and low efficiency. Notably, the IDW as a DNA nanomachine was utilized to construct a sensitive sensing platform for rapid miRNA-21 detection with a limit of detection (LOD) of 19.8 aM and realize the highly sensitive assay of biomarker miRNA-21 in the total RNA lysates of cancer cell. The strategy thus helps in the design of a versatile nucleic acid conversion and signal amplification approach for practical applications in the areas of biosensing assay, DNA nanotechnology, and clinical diagnosis.

Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats.

OBJECTIVE: To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats. METHODS: Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- ß -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting. RESULTS: Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05). CONCLUSION: KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.

Network pharmacological investigation into the mechanism of Kaixinsan powder for the treatment of depression.

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).

Effectiveness of a nurse-led Mindfulness-based Tai Chi Chuan (MTCC) program on Posttraumatic Growth and perceived stress and anxiety of breast cancer survivors.

Background: With the development of positive psychology, posttraumatic growth research on cancer patients has attracted increasing attention from researchers. It is immensely important to effectively increase the posttraumatic growth level of cancer patients and improve their quality of life. Objectives: To investigate the effectiveness of a nurse-led mindfulness-based Tai Chi Chuan (MTCC) programme for increasing posttraumatic growth (PTG) and decreasing the perceived stress and anxiety of breast cancer survivors. Methods: A RCT was conducted. Participants were randomly assigned to either the MTCC group or the control group. The programme included 59 women with stage I-III breast cancer. Participants in the intervention group participated in a nurse-led 8-week, twice a week, one-hour per day mindfulness-based exercise programme. The effectiveness of the intervention was measured three times (T1 - before intervention; T2 - after intervention; T3 - one year after intervention) using validated scales, including the PTG inventory (PTGI), Perceived Stress Scale (PSS), and Self-rating Anxiety Scale (SAS). A repeated-measure analysis of variance model was used to analyse the data. Results: Compared with the wait-list control group, the PTG level in the MTCC group was much higher after the 8-week intervention and the follow-up (F = 374.98, P < .000). The results showed that MTCC increased the level of PTG, and the effect persisted 1 year after intervention. In addition, PSS (F = 55.22, P < .000) and SAS (F = 148.92, P < .000) scores were significantly decreased at T2 and T3. Conclusion: The research preliminarily revealed that the MTCC programme was simple, effective, and more suitable to clinical nurses which should be recommended to cancer survivors to promote their recovery.

Antecedentes: Con el desarrollo de la psicología positiva, la investigación de crecimiento postraumático en pacientes con cáncer ha atraído cada vez más la atención de los investigadores. Es sumamente importante aumentar de manera eficaz el nivel de crecimiento postraumático de los pacientes con cáncer y mejorar su calidad de vida.Objetivos: Investigar la efectividad de un programa de Tai Chi Chuan basado en mindfulness (MTCC en sus siglas en inglés) dirigido por enfermeras para aumentar el crecimiento postraumático (PTG en sus siglas en inglés) y disminuir la percepción de estrés y ansiedad de las sobrevivientes de cáncer de mama.Métodos: Se condujo un ECA. Las participantes fueron asignadas al azar al grupo MTCC o al grupo control. El programa incluyó a cincuenta y nueve mujeres con cáncer de mama en estadio I-III. Las participantes en el grupo de intervención participaron en un programa de ejercicios basados en mindfulness dirigido por enfermeras, de 8 semanas, dos veces por semana, de una hora diaria. La efectividad de la intervención se midió tres veces (T1 ­ antes de la intervención; T2 ­ después de la intervención; T3 ­ un año después de la intervención) usando escalas validadas, incluidas el inventario de PTG (PTGI), la Escala de Estrés Percibida (PSS) y la Escala de Ansiedad Auto-reportada (SAS). Para analizar los datos se utilizó un modelo de análisis de varianza de medidas repetidas.Resultados: En comparación con el grupo control de la lista de espera, el nivel de PTG en el grupo MTCC fue mucho más alto después de intervención de 8 semanas y al seguimiento (F = 374.98, P< 0.000). Los resultados mostraron que la MTCC aumentó los niveles de PTG y el efecto persistió un año después de la intervención. Además, las puntuaciones de PSS (F = 55.22, P< 0.000) y SAS (F = 148.92, P< 0.000) disminuyeron significativamente en T2 y T3.Conclusiones: Las investigaciones preliminares revelaron que el programa de MTCC era simple, efectivo y más adecuado para las enfermeras clínicas, lo que debería recomendarse a las sobrevivientes de cáncer para promover su recuperación.

A branched small molecule-drug conjugate nanomedicine strategy for the targeted HCC chemotherapy.

Off-target toxicity is one of the main challenges faced by anticancer chemotherapeutics. For tumor targeted and precision chemotherapy, we take the advantages of the ligand directed tumor active targeting of small molecule drug conjugates (SMDCs) and the passive tumor targeting of nanoparticles via the enhanced penetration and retention (EPR) effects, put forward a branched small molecule drug conjugate (BSMDC) nanomedicine design concept. In a proof of concept, we used pentaerythritol as the branched moiety, galactosamine (GalN) as the hepatocellular carcinoma (HCC) directing ligands, PTX as a payload, and a stearoyl moiety as the amphiphilic property adjusting group, designed and synthesized BSMDC 1 and prepared its NPs. In cellular level, the BSMDC 1 NPs targeted asialoglycoprotein receptor (ASGPR)-overexpressing HepG2 cells, were effectively taken up in the cells and released in tumor microenvironments, inhibited the HepG2 cell proliferation, arrested HepG2 cell in G2/M phase and induced tumor cell apoptosis. In HepG2 xenograft nude mice, the BSMDC 1 NPs were high specific to target the tumor and demonstrated a higher antitumor efficiency than BSMDC 1, having no apparent influences on mice body weights and major organs, supporting our BSMDC nanomedicine design concept. Therefore, this new strategy may find applications for cancer targeted and precision chemotherapy.

A simple approach to the prediction of soil sorption of organophosphorus pesticides.

Organophosphorus pesticides (OP) affect the crops and environments, and the reliable approach to the prediction of soil sorption of pesticides is required. In this respect, we proposed a simple Chemometrics approach, in which the Tchebichef image moment (TM) method was used to extract useful information from the greyscale images of molecular structures and the quantitative model was established by stepwise regression to predict the soil sorption of OPs. Different squared correlation coefficients including the leave-one-out cross-validation (LOO-CV) (Q2) that concerns the training set and the (R2test) which concerns the external independent test set are more than 0.96. This reflects that the established model has considerably high accuracy and reliability. Compared with the literature on the strategies of quantitative structure-property relationship (QSPR), the proposed method is more suitable, in which the established model shows a high predictive ability. Our study provides another effective approach to predict the soil sorption of OPs and also extends the innovative pathway of QSPR modelling.

Recent Advances in the Development of Casein Kinase 1 Inhibitors.

BACKGROUND: The casein kinase 1 (CK1) family is involved in regulating many cellular processes, including membrane trafficking, DNA damage repair, cytoskeleton dynamics, cytoskeleton maintenance and apoptosis. CK1 isoforms, especially CK1δ and CK1ε have emerged as important therapeutic targets for severe disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), familial advanced sleep phase syndrome and cancer. Due to the importance of CK1 for the pathogenesis of disorders, there are great interests in the development of CK1 inhibitors. METHODS: Using SciFinder® as a tool, the publications about the biology of CK1 and the recent developments of CK1 inhibitors were surveyed with an exclusion of those published as patents. RESULTS: This review presents the current state of knowledge on the development of CK1 inhibitors, including both synthetic small molecular inhibitors that were divided into 7 categories according to structural features, and the natural compounds. An overview of the advancement of CK1 inhibitors was given, with the introduction of various existing CK1 inhibitors, their inhibitory activities, and the structure-activity relationships. CONCLUSION: Through physicochemical characterization and biological investigations, it is possible to understand the structure-activity relationship of CK1 inhibitors, which will contribute to better design and discovery of potent and selective CK1 inhibitors as potential agents for severe disorders such as AD, ALS and cancer.

Study of the controversial resveratrol that interact with the endogenous glutathione thiyl radical in cancer cells.

Found in various natural food products, many in vitro evidence indicated that resveratrol (RES) has been linked to neuroprotective and cardioprotective effects and prevent cancer development. However, human clinical trials have been conducted with varying results, making the usage of RES controversial. In this paper, we demonstrated that the drug RES could be conjugated with the high levels of endogenous GS• in cancer cells. 5,5-Dimethyl-1-Pyrroline-N-Oxide (DMPO) was employed to capture the GS•. The molecular mechanism of the reaction between RES and GS• was further studied by UV-Vis spectrometry, mass spectrometry and Density Functional Theory (DFT) calculations. Besides, the formation of the adduct GS-RES in cancer cell was obtained when RES was added during incubation. Further study indicated that over 77.6% of the RES was consumed in cancer cells. This study suggested that endogenous GS• may be one of the important factors to cause the depletion of anti-tumour drugs during chemotherapy, which should be paid special attention in clinical therapeutics and drug development.

Quality of end-of-life care of advanced cancer patients in mainland China-a retrospective cohort of 441 hospital-death in a public funded comprehensive hospital.

BACKGROUND: Shenzhen is a rapidly growing city in China with a population of over 11 million. The Hong Kong University-Shenzhen Hospital (HKU-SZH) was established in 2012 as a new model of publicly funded health care in mainland China. The clinical oncology center of the HKU-SZH was launched in 2013 which pledged to provide integrated palliative care for advanced cancer patients. This study aims to retrospectively analyze the quality of end-of-life care amongst patients with advanced cancer during their last hospitalization in the HKU-SZH. METHODS: Consecutive patients with advanced solid cancer who passed away in the HKU-SZH from March 2013 to February 2016 were analyzed. Clinical information regarding cancer diagnosis, anticancer treatments, and the aggressiveness of the treatment during the last month of life was recorded. The discussions on the Do-Not-Resuscitate (DNR) order with family members were reviewed. RESULTS: From March 2013 to February 2016, 441 patients with advanced solid cancer passed away in the HKU-SZH. A minority of them (9.3%, 41/441) received cytotoxic chemotherapy in the last month of life. Younger patients had high odds of receiving chemotherapy in their last month of life (OR 2.6, P=0.006). Those who received chemotherapy in their last month of life showed a trend of higher odds of admission to the intensive care unit (OR 2.94, P=0.08). The vast majority of family members / care providers (92.3%, 407/441) consented to the DNR order suggested by oncologists. The rate of DNR acceptance in this cohort was higher than previous reports from mainland China. Within HKU-SZH, the rate was higher in the oncology center than in other departments (OR 5.1, P<0.001). The use of chemotherapy in the last month of life did not associated with the acceptance of DNR (OR 1.3, P=0.23). CONCLUSIONS: The integrated oncology service of the new public hospital HKU-SZH achieved a satisfactory level of end-of-life care in patients with advanced cancer. Further studies are warranted to improve the early integration of palliative care service and to investigate the impact of palliative care on costeffectiveness of oncology service.

Six new dammarane-type triterpene saponins from Panax ginseng flower buds and their cytotoxicity.

BACKGROUND: Panax ginseng has been used for a variety of medical purposes in eastern countries for more than two thousand years. From the extensive experiences accumulated in its long medication use history and the substantial strong evidence in modern research studies, we know that ginseng has various pharmacological activities, such as antitumor, antidiabetic, antioxidant, and cardiovascular system-protective effects. The active chemical constituents of ginseng, ginsenosides, are rich in structural diversity and exhibit a wide range of biological activities. METHODS: Ginsenoside constituents from P. ginseng flower buds were isolated and purified by various chromatographic methods, and their structures were identified by spectroscopic analysis and comparison with the reported data. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide method was used to test their cytotoxic effects on three human cancer cell lines. RESULTS: Six ginsenosides, namely 6'-malonyl formyl ginsenoside F1 (1), 3ß-acetoxyl ginsenoside F1 (2), ginsenoside Rh24 (6), ginsenoside Rh25 (7), 7ß-hydroxyl ginsenoside Rd (8) and ginsenoside Rh26 (10) were isolated and elucidated as new compounds, together with four known compounds (3-5 and 9). In addition, the cytotoxicity of these isolated compounds was shown as half inhibitory concentration values, a tentative structure-activity relationship was also discussed based on the results of our bioassay. CONCLUSION: The study of chemical constituents was useful for the quality control of P. ginseng flower buds. The study on antitumor activities showed that new Compound 1 exhibited moderate cytotoxic activities against HL-60, MGC80-3 and Hep-G2 with half inhibitory concentration values of 16.74, 29.51 and 20.48 µM, respectively.

Nomograms predicting long-term survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: A population-based study.

BACKGROUND: There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas. AIM: To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas. METHODS: Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance, Epidemiology, and End Results database, and randomly divided into the training (n = 853) and the validation (n = 366) cohorts. Based on the Cox regression model, nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient. The performance of the nomograms was measured according to discrimination, calibration, and clinical utility. Moreover, we compared the predictive accuracy of the nomograms with that of the traditional staging system. RESULTS: In the training cohort, age, marital status, histological type, T stage, N stage, M stage, and chemotherapy were selected to construct nomograms. Compared with the American Joint Committee on Cancer 7th staging system, the nomograms were generally more discriminative. The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction. Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system. With respect to decision curve analyses, the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities. CONCLUSION: The nomograms show improved predictive accuracy, discrimination capability, and clinical utility, which can be used as reliable tools for risk classification and treatment recommendations.

Simultaneous quantification of multiple endogenous biothiols in cancer cells based on a multi-signal fluorescent probe.

Although a large number of fluorescent probes have been developed, the simultaneous quantitative analysis of intracellular thiols is still difficult due to the spectral overlap and the complexity of the intracellular environment. In this study, a multi-signal fluorescent probe was employed for the simultaneous quantification of intracellular glutathione (GSH), cysteine (Cys) and homocysteine (Hcy). As the feature variables of the target components, the Tchebichef image moments (TMs) calculated from the grayscale images of the 3D fluorescence spectra were used to establish the quantitative linear models by stepwise regression. The intra-day and inter-day precisions of the proposed method were less than 5.6% and 8.7%, respectively. The recoveries ranged from 97.0% to 105.9%. In addition, the proposed approach was applied to the simultaneous quantitative determination of Cys, GSH and Hcy in the MCF-10A cell (a type of normal cell) and MDA-MB-231 cancer cell. The obtained results indicated that the concentrations of the three thiols in the cancer cell were higher than those in the normal cell. This study not only provides an effective approach for the quantification of multi-target bio-molecules in complicated intracellular environments, but also further extends the applications of multi-signal fluorescent probes, which will promote the design of new multi-signal fluorescent probes.

The rapid quantitative analysis of three pesticides in cherry tomatoes and red grape samples with Tchebichef image moments.

Diverse interferences often affect the determination of pesticide residues in various kinds of food, and complex pretreatments are necessary. An effective approach for the simultaneous quantitative analysis of multi-target components in different substrates was proposed, and applied to the determination of ternary pesticides in cherry tomatoes and red grape samples. By means of HPLC-DAD, the spectra were obtained under isocratic elution. Utilizing the Tchebichef image moments, unified quantitative models were established for the three target components in the samples with two different substrates, respectively. The correlation coefficients of leave-one-out cross-validation (Rloo-cv2) of the obtained models were more than 0.9975. The predictive correlation coefficients (Rp2) were more than 0.9831. Compared with the N-PLS and MCR-ALS methods, the proposed approach is not only more accurate and reliable, but also can extract essential information and expected to be a potential tool to rapidly quantify multi-component in different substrates without complex pretreatments.

Cytotoxic epimeric ginsenosides from the flower buds of Panax ginseng.

Three pairs of ginsenoside epimers, including three new compounds (2, 3 and 5), were isolated from the flower buds of Panax ginseng. The structures of the isolated compounds were elucidated on the basis of considerable spectroscopic analyses and comparison with the reported data. All six compounds were evaluated for their cytotoxicties against three human cancer cell lines, HL-60, MGC80-3 and Hep-G2. Compounds 1, 3, and 6 with S configurations at C-24 or C-20 showed moderate inhibitory activities with IC50 values of 25.32, 18.76, and 38.64 µM in HL-60 cells, respectively. Our findings showed that different configurations of these isolated ginsenosides had a significant impact on the antitumor activity, and S epimers were higher than R.

No significant association between PIK3CA mutation and survival of esophageal squamous cell carcinoma: A meta-analysis.

The prognostic value of phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) in patients with esophageal squamous cell carcinoma (ESCC) is controversial. We aimed to investigate the prognostic significance of PIK3CA mutation in patients with ESCC. EMBASE, PubMed, and Web of Science databases were systematically searched from inception through Oct. 3, 2016. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using a random effects model for overall survival (OS) and disease-free survival (DFS). Seven studies enrolling 1505 patients were eligible for inclusion of the current meta-analysis. Results revealed that PIK3CA mutation was not significantly associated with OS (HR: 0.90, 95% CI: 0.63-1.30, P=0.591), with a significant heterogeneity (I 2=65.7%, P=0.012). Additionally, subgroup analyses were further conducted according to various variables, such as types of specimen, the sample size, technique and statistical methodology. All results suggested that no significant relationship was found between PIK3CA mutation and OS in patients with ESCC. For DFS, there was no significant association between PIK3CA mutation and DFS in patients with ESCC (HR: 1.00, 95% CI=0.47-2.11, P=0.993, I 2=73.7%). Publication bias was not present and the results of sensitivity analysis were very stable in the current meta-analysis. Our findings suggest that PIK3CA mutation has no significant effects on OS and DFS in ESCC patients. More well-designed prospective studies with better methodology for PIK3CA assessment are required to clarify the prognostic significance of PIK3CA mutation in ESCC patients.

Ameliorating effect of Klotho on endoplasmic reticulum stress and renal fibrosis induced by unilateral ureteral obstruction.

INTRODUCTION: Expression of Klotho is decreased and endoplasmic reticulum (ER) stress is activated in patients with chronic kidney disease. This study aimed to investigate the effect of Klotho protein on ER stress-related apoptosis and renal fibrosis in rates with unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: Twenty-four rats were divided into the sham, UUO, and Klotho treatment groups. Renal interstitial fibrosis model was induced by UUO in the rats of the latter two groups. Soluble Klotho protein was injected into the abdominal cavity. Serum and kidney samples were collected 14 days after the UUO surgery for examination of renal injury and renal interstitial fibrosis using hematoxylin-eosin and Masson trichrome staining methods. The level of apoptotic cells was assessed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Expression of 3 ER stress-related proteins including glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, and caspase-12 were measured. RESULTS: Kidney dysfunction, increased renal injury index, and aggravated renal fibrosis were documented in the UUO group. Expression of Klotho in the UUO rats was remarkably decreased (P < .05) and expression of all three ER stress-related proteins were significantly upregulated, accompanied by increasing numbers of apoptotic cells (P < .05). Soluble Klotho administration improved kidney function, ameliorated pathological changes, decreased expressions of ER-stress related-proteins, and reduced the number of apoptotic cells. CONCLUSION: Unilateral ureteral obstruction decreased Klotho expression and activated ER stress and related apoptosis. Klotho administration ameliorated UUO-induced ER stress, inhibited apoptotic process, and attenuated renal fibrosis.

A new aurone glycoside from Veratrum dahuricum (Turcz.) Loes. f.

To study the chemical constituents of Veratrum dahuricum (Turcz.) Loes. f., a new aurone glycoside named as (Z)-7, 4'-dimethoxy-6-hydroxyl-aurone-4-O-ß-glucopyranoside was isolated from the 95% ethanol extracts of the rhizomes and roots of Veratrum dahuricum (Turcz.) Loes. f. by repeated column chromatography on silica gel and recrystallization. Its structure was established by extensive spectroscopic analyses, and its cytotoxicities against HepG-2, MCF7 and A549 cell lines were measured in vitro.

[Signal transducers and activators of transcription-3 modulates human squamous cell carcinoma invasion via targeting mircoRNA-21 in vitro].

OBJECTIVE: To investigate the effect and mechanism of signal transducers and activators of transcription 3 (STAT-3) modulates human tongue squamous cell carcinoma invasion ability via targeting mircoRNA-21. METHODS: Tscca and Tca8113P160 human tongue squamous cell carcinoma cell lines were used.WP1066 (STAT-3 inhibitor) , the small molecule inhibitor of STAT-3 was used to suppress the STAT-3 expression. The half maximal inhibitory concentration (IC50 value) of WP1066 in the two cell lines was determined by methyl thiazolyl tetrazolium (MTT) assay. The expression level of STAT-3 and phosphorylation of STAT-3 (pSTAT-3) was examined by Western blotting. Real-time PCR was used to detect the mircoRNA-21 expression after treated with WP1066. Matrigel matrix and transwell assay were used to determine cancer cell colony formation and invasion ability after treated with WP1066. Tumor invasion related proteins in Tscca and Tca8113P160 cell lines were measured by Western blotting. Luciferase reporter gene assay was conducted to detect the relationship between STAT-3 and mircoRNA-21. RESULTS: The IC50 to WP1066 in Tscca cell was 3.1 and 3.5 µmol/L for Tca8113P160 cell respectively. STAT-3/pSTAT-3 protein level was suppressed significantly (Tscca: STAT-3: F = 887.154, P = 0.000; pSTAT-3: F = 332.212, P = 0.000; Tca8113P160: STAT-3: F = 322.895, P = 0.000; pSTAT-3:F = 788.357, P = 0.000). mircoRNA-21 expression was down-regulated (Tscca:F = 32.157, P = 0.000; Tca8113P160: F = 11.349, P = 0.007). The diameters of culture clone in cell treated with WP1066 were less than control groups (Tscca:F = 15.751, P = 0.004; Tca8113P160: F = 12.964, P = 0.007). The number of tongue cancer cell migrating through the transwell membrane in WP1066 treated group was less than in control groups (Tscca: F = 1688.926, P = 0.000; Tca8113P160: F = 327.528, P = 0.000). In addition, MMP-2/9 protein expression was decreased in both of the cell lines treated with WP1066, while TIMP-3 was up regulated dramatically. STAT-3 could modulate mircoRNA-21 directly. CONCLUSIONS: Reduction of STAT-3 can inhibit tongue cancer cell invasion ability via targeting mircoRNA-21.