Clinical observations in treatment of lower extremity varicose veins with trigger points acupuncture.

OBJECTIVES: To observe the effect of the acupuncture of myofascial trigger points (MTrPs) in the treatment of lower extremity varicose veins (LEVVs). METHODS: Overall, 260 patients with LEVVs participated in this study. LEVVs were selected based on diagnostic criteria of Clinical, Etiology, Anatomy, and Pathophysiology levels 2-5 and classified into six types on the basis of their anatomical positions. The MTrPs in the lower extremities were localized in accordance with the classification of LEVVs and treated by MTrPs acupuncture combined with self-massage and self-stretching. The interval between each treatment was 2 weeks to 1 month, depending on needling pain tolerance of each patient. An in-house evaluation was used to estimate the proportion of varicose veins in the lower limbs and their accompanying symptoms. The treatment effect was evaluated before each treatment and at 1-year follow-up. RESULTS: The mean evaluation score of LEVVs before the treatment course was 3.66 ± 1.19. After the course, this reduced to 1.18 ± 0.97, with the following response rates: 85% for excellent and good and 15% for medium. After 1-year follow-up, the mean evaluation score of all patients was 1.11 ± 0.92, with the following response rates: 87% for excellent and good, and 13% for medium. CONCLUSIONS: In some patients, MTrP acupuncture could cure LEVVs and its accompanying symptoms. These LEVVs are probably caused by fascia tension as a pre-pathology induced by the MTrPs.

Effect of Low-Load Blood Flow Restriction Training on Patients With Functional Ankle Instability: A Randomized Controlled Trial.

CONTEXT: Decreased muscle strength and balance in patients with functional ankle instability (FAI) can be effectively improved by ankle strength training. Low-load blood flow restriction (LL-BFR) training increases muscle size and strength, but there is limited evidence from studies on muscle strength and balance in FAI patients. OBJECTIVE: To study the effects of LL-BFR training versus high-load training (HLT) on muscle strength and balance in FAI patients. DESIGN: Randomized controlled trial. PARTICIPANTS: Forty-six young adults with a history of FAI. INTERVENTIONS: Participants in the LL-BFR and HLT groups performed 4 sets (30 × 15 × 15 × 15) of ankle training at 20% to 40% of the one-repetition maximum and 70% to 85% one-repetition maximum, respectively, twice a week for 6 weeks. MAIN OUTCOME MEASURE(S): Plantar flexion, dorsiflexion, inversion, and eversion muscle strength, and the Y-balance test scores were assessed at baseline and after 3 and 6 weeks; the thickness of the tibialis anterior, triceps surae, and peroneus longus muscles were assessed at baseline and after 6 weeks. RESULTS: Inversion, eversion, dorsiflexion, and plantar flexion muscle strength; tibialis anterior, triceps surae, and peroneus longus thickness; and Y-balance test scores were significantly increased in the LL-BFR group after 3 and 6 weeks compared with baseline (P < .05), with no significant difference between the LL-BFR and HLT groups after 6 weeks (P > .05). However, at the end of 3 weeks, eversion muscle strength and Y-balance test scores were significantly higher in the LL-BFR group than in the HLT group (P < .05). CONCLUSIONS: Over 6 weeks, LL-BFR training was as effective as HLT in improving ankle muscle strength, muscle thickness, and balance in FAI patients, but LL-BFR training improved the ankle eversion muscle strength and dynamic balance more than HLT did in the early stages of the intervention. This finding will provide a new intervention strategy for the clinical rehabilitation of FAI patients.

Morusinol extracted from Morus alba induces cell cycle arrest and apoptosis via inhibition of DNA damage response in melanoma by CHK1 degradation through the ubiquitin-proteasome pathway.

BACKGROUD: Flavonoids have a variety of biological activities, such as anti-inflammation, anti-tumor, anti-thrombosis and so on. Morusinol, as a novel isoprene flavonoid extracted from Morus alba root barks, has the effects of anti-arterial thrombosis and anti-inflammatory in previous studies. However, the anti-cancer mechanism of morusinol remains unclear. PURPOSE: In present study, we mainly studied the anti-tumor effect of morusinol and its mode of action in melanoma. METHODS: The anti-cancer effect of morusinol on melanoma were evaluated by using the MTT, EdU, plate clone formation and soft agar assay. Flow cytometry was used for detecting cell cycle and apoptosis. The É£-H2AX immunofluorescence and the alkaline comet assay were used to detect DNA damage and the Western blotting analysis was used to investigate the expressions of DNA-damage related proteins. Ubiquitination and turnover of CHK1 were also detected by using the immunoprecipitation assay. The cell line-derived xenograft (CDX) mouse models were used in vivo to evaluate the effect of morusinol on tumorigenicity. RESULTS: We demonstrated that morusinol not only had the ability to inhibit cell proliferation, but also induced cell cycle arrest at G0/G1 phase, caspase-dependent apoptosis and DNA damage in human melanoma cells. In addition, morusinol effectively inhibited the growth of melanoma xenografts in vivo. More strikingly, CHK1, which played an important role in maintaining the integrity of cell cycle, genomic stability and cell viability, was down-regulated in a dose- and time-dependent manner after morusinol treatment. Further research showed that CHK1 was degraded by the ubiquitin-proteasome pathway. Whereafter, morusinol-induced cell cycle arrest, apoptosis and DNA damage were partially salvaged by overexpressing CHK1 in melanoma cell lines. Herein, further experiments demonstrated that morusinol increased the sensitivity of dacarbazine (DTIC) to chemotherapy for melanoma in vitro and in vivo. CONCLUSION: Morusinol induces CHK1 degradation through the ubiquitin-proteasome pathway, thereby inducing cell cycle arrest, apoptosis and DNA damage response in melanoma. Our study firstly provided a theoretical basis for morusinol to be a candidate drug for clinical treatment of cancer, such as melanoma, alone or combinated with dacarbazine.

A bibliometric analysis study of blood flow restriction using CiteSpace.

[Purpose] To assess the current state-of-the-art and the prevailing trends regarding the global use of blood flow restriction (BFR) in the past 20 years. [Participants and Methods] We retrieved literature relating to BFR from 1999 to 2020 using Web of Science. We conducted a bibliometric analysis of countries/institutions, cited journals, authors/cited authors, cited references, and keywords using CiteSpace. An analysis of counts and centrality was used to examine publication output, countries/institutions, core journals, active authors, foundation references, hot topics, and frontiers. [Results] Seven hundred seventy five references were included and the total number of publications has been continually increasing over the investigated period. Representatives of important academic groups are the Japanese scholars from the University of Tokyo as represented by Takashi Abe. Jeremy Paul Loenneke's article (centrality: 0.15) was the most representative and symbolic reference with the highest centrality. The three topics identified were intervention (intensity resistance exercise, IRE), physiology (ischemia and muscular function) and behavior (adaptation and increase). The four frontier topics were phosphorylation, reduction, low intensity and arterial occlusion. [Conclusion] This study provides an insight into BFR and offers valuable information for BFR researchers to identify new perspectives for potential cooperation with collaborators and their related cooperative institutions.

Effectiveness of low-level gallium aluminium arsenide laser therapy for temporomandibular disorder with myofascial pain: A systemic review and meta-analysis.

PURPOSE: Temporomandibular disorder (TMD) causes masticatory muscle pain and mouth opening limitations and affects patients' ability to eat, practice oral health and perform other activities of daily living. Although the benefits of low-energy lasers in treating TMD have been reported, the results vary greatly depending on the equipment used and the energy output. This study systematically evaluated the efficacy of a low-level gallium aluminium arsenide (GaAlAs) laser treatment for TMD with myofascial pain and maxillary pain. METHODS: We searched the PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) published since database inception to April 5, 2020, that compared low-level laser treatment to sham/placebo treatment or no intervention in patients suffering from TMD with myofascial pain. Three reviewers independently screened the literature, extracted data, and assessed the quality of the included studies according to the risk-of-bias tool recommended by the Cochrane Handbook V.5.1.0 (Cochrane Collaboration, London, UK). Then, a meta-analysis was performed using RevMan 5.3 and Stata 15.1 software. RESULTS: The data from 8 randomized controlled trials including 181 patients were analyzed. The severity of myofascial TMD pain (measured on a visual analogue scale, VAS) at the end of treatment was significantly different between the control laser therapy and the low-level GaAlAs laser therapy (weighted mean difference [WMD] = -0.76, 95% confidence interval [CI] -1.51 to 0.01, P = .046); at 3 to 4 weeks after treatment, there was no significant difference (WMD = 1.24, 95% CI -0.04 to 2.51, P = .057). In addition, there was no significant improvement in maximum mouth opening (MMO) at the end of treatment (WMD = -0.03, 95% CI -4.13 to 4.06, P = .987) or at 3 to 4 weeks after treatment (WMD = 1.22, 95% CI -2.94 to 5.39, P = .565). CONCLUSIONS: The results of this study suggest that there is insufficient evidence to indicate an efficacy of low-level GaAlAs laser therapy in improving TMD pain and maximal oral opening. These results suggest that clinicians should make appropriate recommendations to inform patient decision-making.

The Impact of Air Pollution on Outpatient Visits of Children with Asthma in Xi'an, China.

INTRODUCTION: The number of children with asthma has increased significantly in China. In recent years, there has been a steady increase in outpatient visits of children with asthma, attributed to poor air quality and environmental pollution reported regionally and at our institution. This study aimed to assess the association between air pollution and the number of outpatient visits of children with asthma in Xi'an, the largest city in northwest China. METHODS: We searched the database of the largest children's hospital in Xi'an for related information from 2014 to 2018 and then acquired data on air pollution, including the daily average concentrations of fine particles (PM2.5), inhalable particles (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) of that same time period. Time-series generalized additive models were used to analyze the relationships. RESULTS: Our results revealed that air pollution was very serious in Xi'an, with elevated average concentrations of PM2.5, PM10, and NO2 from 2015 to 2018. The relative risk of outpatient visits due to asthma associated with PM2.5, PM10, and SO2 pollution rose significantly and reached 1.11 (1.02-1.21), 1.25 (1.01-1.55), and 1.71 (1.31-2.25), respectively, when there was a 10 ug·m-3 increase in concentration, during a lag of 21 d. CONCLUSIONS: A high concentration of particulate matter (PM2.5 and PM10) was the prominent feature of air pollution in Xi'an. Exposure to air pollutant (PM2.5, PM10, SO2) was positively associated with an increased risk of children's outpatient visits for asthma in Xi'an.

Ghrelin Affects Gastric Cancer Progression by Activating AMPK Signaling Pathway.

As the endogenous ligand for the GH secretagogue receptor (GHSR), Ghrelin is aberrant expressed in multiple malignant carcinoma, and involved in regulating a number of progression of cancer, especially in metastasis and proliferation. However, the precise role of Ghrelin in tumorigenesis of gastric cancer (GC) is still poorly understood. In this study, we extensively investigated the roles and mechanisms of Ghrelin in human gastric cancer. Ghrelin levels in cancer tissues and cell lines were analyzed by immunohistochemistry, qRT-PCR, and Western blot. Functional studies were performed after Ghrelin overexpressed or knockdown in AGS cell line. Cell proliferation was evaluated in by MTT and clone formation assays. The wound healing and Transwell system were used to assess the cell migration and invasive ability of GC cells. Cell apoptosis was detected by flow cytometry, and metabolic assays were performed to reveal the function of Warburg effect in the process. Ghrelin was lowly expressed in gastric cancer tissues and cell lines. Overexpression of Ghrelin inhibited gastric cancer cell proliferation, migration, invasion, and promoted apoptosis by activating the AMPK pathway, while D-[lys3]-GHRP-6 (a GHSR agonist) treatment relieved the effect, promoting tumorigenesis. Ghrelin knockdown increased the glucose uptake and lactic acid release, suggesting that Ghrelin elicited an anti-Warburg effect via AMPK pathway to inhibit gastric tumorigenesis. Ghrelin inhibits cell proliferation, migration, and invasion by eliciting an anti-Warburg effect via AMPK signaling pathway in gastric cancer cells.

FOXO3a­SIRT6 axis suppresses aerobic glycolysis in melanoma.

Melanoma, the most aggressive human skin tumor, has a very short survival time, and there are currently no effective treatments. Alterations in cell metabolism, such as enhanced aerobic glycolysis, have been identified as hallmarks of cancer cells. In the present study, bioinformatics studies using online databases revealed that FOXO3a expression was lower in melanoma tissues compared with normal tissues and nevus. Additionally, Kaplan­Meier analysis showed that high expression of FOXO3a predicted an improved prognosis for patients with melanoma. Furthermore, Pearson correlation analysis indicated that the expression of FOXO3a was positively correlated with SIRT6 expression and negatively correlated with the expression levels of a number of glycolysis­associated genes. Chromatin immunoprecipitation and luciferase assays showed that FOXO3a was enriched in the SIRT6 promoter region and promoted its transcription. Then, SIRT6 was overexpressed in FOXO3a­knockdown MV3 cells and downregulated in FOXO3a­overexpressing MV3 cells by using lentivirus­mediated stable infection. The results showed that SIRT6 knockdown or overexpression rescued the effects of FOXO3a overexpression or knockdown, respectively, on glycolysis, as determined by glucose uptake, glucose consumption and lactate production assays, the expression of glycolytic genes and glucose stress flux tests. SIRT6 overexpression also suppressed FOXO3a knockdown­induced tumor growth in a mouse model. The present findings indicated that the FOXO3a­SIRT6 regulatory axis inhibited glucose metabolism and tumor cell proliferation in melanoma, and provided novel insight into potential therapeutic strategies to treat this disease.

The application of musculoskeletal ultrasonography in sports injuries of lower limbs in Chongqing Marathon competition.

BACKGROUND: High incidence of sports injury occurring during marathon competitions urges a pressing demand for a convenient and accurate diagnostic tool of such injuries. However, contemporary information on the application of musculoskeletal ultrasonography (MSUS) in sports injury is not sufficient. METHODS: A repeated measures study was used to describe the distribution of lower limb injuries in the Chongqing marathon and the application of MSUS in assessing these sports injuries. To verify the diagnostic accuracy of MSUS for sports injury, participants were assigned to group A (MSUS group) or group B (Sports medicine physician, i.e. SMP group), each group had an independent procedure of making a diagnosis. That is, ultrasound physicians in group A made a diagnosis from the ultrasonographic images while sports medicine physicians in group B synthesizing symptoms and signs of patients to identify the exact injury. RESULTS: No statistically significant difference was found in the participants of the baseline characteristics between the two groups (P>0.05). In both groups, the knee was accounted as the vast majority of running injury sites, followed by the ankle (P=0.152). Tendons and ligaments injuries (χ2=48.437 and P=0.000) were the most common types of injury. Visual Analog Scale (VAS), a higher score of which indicates severer pain (0 to 10), was used to evaluate the severity of pain from injuries. VAS scores decreased significantly (P<0.05) in both groups after immediate treatment and the decrease in group A was significantly greater than group B (P=0.007). For athletes with pain sustained or exacerbated, further MRI exam showed a concordance rate of approximately 100% between MSUS and MRI diagnosis. CONCLUSIONS: Musculoskeletal ultrasonography could be applied as an efficient method for the diagnosis of sports injuries in the athletic competition field.

Effects of ß­hydroxybutyric acid and ghrelin on the motility and inflammation of gastric antral smooth muscle cells involving the regulation of growth hormone secretagogue receptor.

Ghrelin is an orexigenic hormone that is produced by gastric cells. Ghrelin stimulates food intake and increases gastric movement. In rat model, injected ß­hydroxybutyric acid (ß­HB) leads to a decrease in body weight. It has been reported that patients with gastric erosions are slower to evacuate the stomach. The aim of the present study was to investigate the effects of ghrelin and ß­HB on motility and inflammation in rat gastric antral smooth muscle cells (GASMCs). GASMCs were extracted from rat gastric antrum. Cell viability was determined using the Cell Counting Kit­8 assay. A reactive oxygen species (ROS) assay kit was used to analyze the levels of ROS using flow cytometry. Protein levels were determined using western blotting, and the expression levels of mRNAs were evaluated using reverse transcription­quantitative PCR. ß­HB inhibited the expression of myosin regulatory light polypeptide 9 (MYL9), myosin light chain kinase (MLCK), transforming protein RhoA (RhoA), Rho­associated protein kinase­1 (ROCK­1) and growth hormone secretagogue receptor (GHS­R). By contrast, ghrelin increased the expression of MYL9, MLCK, RhoA, ROCK­1 and GHS­R in ß­HB­treated GASMCs. ß­HB increased the levels of tumor necrosis factor (TNF)­α, interleukin (IL)­6 and ROS, and decreased the levels of manganese (Mn) superoxide dismutase (SOD), copper/zinc (Cu/Zn)SOD and catalase. Ghrelin decreased the expression of TNF­α, IL­6, ROS and catalase, whereas ghrelin promoted the expression of MnSOD and Cu/ZnSOD in ß­HB­treated GASMCs. Short interfering RNA targeting GHS­R inhibited the expression of MYL9, MLCK, RhoA and ROCK­1, and increased the levels of TNF­α, IL­6 and ROS in ß­HB­treated or ghrelin­treated GASMCs. The present study provided preliminary evidence that ß­HB inhibits the motility of GASMCs and promotes inflammation in GASMCs, whereas ghrelin decreases these effects. GHS­R acted as a primary regulator of motility and inflammation in GASMCs treated with ß­HB and ghrelin.

[Effect of electroacupuncture on degradation of myosin heavy chain of gastrocnemius muscle in diabetes rats].

OBJECTIVE: To explore the effect of electroacupuncture（EA）on the expression of muscle-specific ring finger protein 1（MuRF1/Trim63），F-box only protein 32（Fbxo32），myosin heavy chain-IIa（Myh2），myosin heavy chain-IIb（Myh4）and myosin heavy chain-I（Myh7）in diabetes rats. METHODS: Thirty-six male Wistar rats were equally randomized into control, model and EA groups. The diabetes model was established by intraperitoneal injection of 0.1% Streptozocin (STZ) solution (50 mg/kg). After that, EA (2 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36), "Yinlingquan" (SP9) and "Shenshu" (BL23) for 10 min, once a day, 6 times a week for 2 weeks. The fasting blood glucose (FBG) and fasting serum insulin (FINS) contents were assayed by using ELISA, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The body weight, and wet weight of bilateral gastrocnemius muscles were measured. The cross-sectional area (CSA) of the gastrocnemius muscle was measured after H.E. stai-ning. The expression of MuRF1, Fbxo32, Myh2, Myh4 and Myh7 mRNAs in the gastrocnemius tissue was tested using quantitative real time-PCR. RESULTS: Compared with the control group, the FBG and HOMA-IR were significantly higher (P<0.05), and the FINS, body weight were significantly lower (P<0.05) after intravenous injection of STZ for 1, 2, 3, 4, 5 weeks respectively. Following EA treatment and compared with the model group, the FBG and HOMA-IR were significantly down-regulated (P<0.05), and the FINS and body weight were considerably increased (P<0.05). Following modeling and compared with the control group, the wet weight of gastrocnemius muscle, CSA, and expression levels of Myh2, Myh4 and Myh7 mRNAs were obviously decreased, and the expression of MuRF1 and Fbxo32 mRNA was obviously increased in the model group (P<0.05). After EA treatment, the gastrocnemius muscle wet weight, CSA, expression levels of Myh2, Myh4 and Myh7 mRNA were significantly up-regulated (P<0.05), and the expression levels of MuRF1 and Fbxo32 mRNA were markedly down-regulated in comparison with those of the model group (P<0.05). CONCLUSION: EA treatment can delay the atrophy of gastrocnemius muscle (skeletal muscle) in diabetes rats possibly by improving the degradation of myosin heavy chain via regulating the expression of muscular MuRF1, Fbxo32, Myh2, Myh4 and Myh7 mRNAs.

[Functionalized genetic engineered silk-based biomaterials and their applications].

Silk-based biomaterials are featured with excellent mechanical properties, good biocompatibility and biodegradability, which contribute to their potential applications in biomedical field. The current recognition of silk protein materials in structure and function provides a basic theory for the transformation of silk protein into new types of biomaterials. In addition, exogenous sequences encoding new peptide or structural domain can be inserted into the maternal gene sequences encoding silk proteins through genetic engineering technology to synthesize novel silk-based biomaterials with unique functions. This review summarizes the current trend and development perspective of genetically engineered functional silk-based materials for biomedical applications.

DC Shifts-fMRI: A Supplement to Event-Related fMRI.

Event-related fMRI have been widely used in locating brain regions which respond to specific tasks. However, activities of brain regions which modulate or indirectly participate in the response to a specific task are not event-related. Event-related fMRI can't locate these regulatory regions, detrimental to the integrity of the result that event-related fMRI revealed. Direct-current EEG shifts (DC shifts) have been found linked to the inner brain activity, a fusion DC shifts-fMRI method may have the ability to reveal a more complete response of the brain. In this study, we used DC shifts-fMRI to verify that even when responding to a very simple task, (1) The response of the brain is more complicated than event-related fMRI generally revealed and (2) DC shifts-fMRI have the ability of revealing brain regions whose responses are not in event-related way. We used a classical and simple paradigm which is often used in auditory cortex tonotopic mapping. Data were recorded from 50 subjects (25 male, 25 female) who were presented with randomly presented pure tone sequences with six different frequencies (200, 400, 800, 1,600, 3,200, 6,400 Hz). Our traditional fMRI results are consistent with previous findings that the activations are concentrated on the auditory cortex. Our DC shifts-fMRI results showed that the cingulate-caudate-thalamus network which underpins sustained attention is positively activated while the dorsal attention network and the right middle frontal gyrus which underpin attention orientation are negatively activated. The regional-specific correlations between DC shifts and brain networks indicate the complexity of the response of the brain even to a simple task and that the DC shifts can effectively reflect these non-event-related inner brain activities.

Single-Trial EEG-fMRI Reveals the Generation Process of the Mismatch Negativity.

Although research on the mismatch negativity (MMN) has been ongoing for 40 years, the generation process of the MMN remains largely unknown. In this study, we used a single-trial electro-encephalography (EEG)-functional magnetic resonance imaging (fMRI) coupling method which can analyze neural activity with both high temporal and high spatial resolution and thus assess the generation process of the MMN. We elicited the MMN with an auditory oddball paradigm while recording simultaneous EEG and fMRI. We divided the MMN into five equal-durational phases. Utilizing the single-trial variability of the MMN, we analyzed the neural generators of the five phases, thereby determining the spatiotemporal generation process of the MMN. We found two distinct bottom-up prediction error propagations: first from the auditory cortex to the motor areas and then from the auditory cortex to the inferior frontal gyrus (IFG). Our results support the regularity-violation hypothesis of MMN generation.

[Advances in mesenchymal to epithelial transition factor signaling pathway and inhibitors].

As a receptor tyrosine kinase, mesenchymal to epithelial transition factor (MET) is the membrane receptor for hepatocyte growth factor (HGF), which is related with a series of biological functions, such as cell proliferation, progression, apoptosis, metastasis and morphological changes. As research continues, MET is amplified or overexpressed in a wide range of human cancers and closely related with worse prognosis. Therefore, various MET inhibitors are currently being developed as potential treatments for a variety of cancers. Based on our current study we summarize the existing knowledge on structure, biological function and its inhibitors of MET and provide a data phase for future researchers.

Demethylzeylasteral inhibits cell proliferation and induces apoptosis through suppressing MCL1 in melanoma cells.

Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells. MCL1 is an anti-apoptotic protein in BCL2 family, and amplifies frequently in multiple human cancers. MCL1 is also known as a potential contributor for the resistance of BCL2 inhibitors, as well as various chemotherapeutic drugs. MCL1 is, therefore, regarded as a potential target for cancer therapy. Here, for the first time, we unveil that demethylzeylasteral suppresses the expression of MCL1. Interestingly, MCL1 interacts with S phase-related protein CDK2, and thereby inhibits it's ubiquitin-dependent degradation. Together, demethylzeylasteral is a promising anti-tumor compound in melanoma cells. Demethylzeylasteral is also a potential inhibitor of MCL1.

MicroRNA-9 expression is a prognostic biomarker in patients with osteosarcoma.

BACKGROUND: The purpose of the present study was to examine the expression levels of microRNA-9 (miR-9) in osteosarcoma tissues and normal bone tissues, and investigate the relationships between miR-9 expression, clinicopathological features and the prognosis of patients with osteosarcoma. METHODS: The expression levels of miR-9 in osteosarcoma tissues and corresponding non-cancerous tissues were detected using a real-time quantitative assay. Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. RESULTS: Compared to non-cancerous bone tissues, the expression levels of miR-9 in osteosarcoma tissues were significantly elevated (P < 0.001). We found that the expression level of miR-9 was significantly associated with tumor size (P = 0.011), clinical stage (P = 0.009) and distant metastasis (P < 0.001). The Kaplan-Meier curve showed that patients with low miR-9 expression survived significantly longer than patients with high miR-9 expression (P = 0.0017). Multivariate analysis suggested that miR-9 expression level (P = 0.002) is an independent prognostic factors for overall survival. CONCLUSIONS: The findings of our study suggest that increased miR-9 expression has a strong correlation with the aggressive progression of osteosarcoma and its overexpression is a statistically significant risk factor affecting overall survival, suggesting that increased miR-9 expression could be a valuable marker of tumor progression and for prognosis of osteosarcoma.

ZIP1 and zinc inhibits fluoride-induced apoptosis in MC3T3-E1 cells.

Excess fluoride intake could induce apoptosis in the cells. As an essential micronutrient and cytoprotectant, zinc is involved in many types of apoptosis. Here, we studied the effects of zinc and ZIP1 on fluoride-induced apoptosis in mouse MC3T3-E1 cells and examined the underlying molecular mechanisms. Our study found that fluoride not only inhibited cell proliferation and increased the intracellular reactive oxygen species (ROS) but also induced cell apoptosis. Whereas pretreatment with zinc significantly attenuated fluoride-induced ROS production and partly protected cells against fluoride-induced apoptosis through MAPK/ERK signaling pathway. Our study also found that fluoride upregulated the expression of ZIP1 in a time-dependent manner. Moreover, overexpression of ZIP1 also inhibited fluoride-induced apoptosis by activation of PI3K/Akt pathway. This cytoprotective effect of zinc and ZIP1 may be new factors that affect the physiological activity of fluoride and need study further.

[Synthesis of baicalin-copper and baicalin-aluminium complex and its bioactivity].

OBJECTIVE: To study synthesis of baicalin-copper and baicalin-aluminium complex and its antimicrobial, anti-tumor activity and anti-tumor effect against macrophages. METHOD: Baicalin was reacted with metallic salt under a weak base condition to produce baicalin-copper and baicalin-aluminium complex. Baicalin and its synthesized complex were detected for antimicrobial activity against Staphylococcus aureus, Hay bacillus, Escherichia coli, Salmonella and Candida albicans by twofold broth dilution technique. Their anti-tumor activity against A549 and IC50 of HepG2 cells and anti-tumor effect against macrophages were detected by the MTT. And their phagocytic effect on macrophages was determined by the neutral red assay. RESULT: The yields of baicalin-copper and baicalin-aluminium complex were 73.93% and 91.08%, respectively. The minimum inhibitory concentration (MIC) value against Staphylococcus aureus, Hay bacillus, Escherichia coli, Salmonella and Candida albicans was 0.0004, 0.0009, 0.0004, 0.0009, 0.000 4 mol x L(-1) for baicalin-copper complex and 0.0011, 0.0011, 0.0011, 0.0011, 0.0005 mol x L(-1) for baicalin-aluminium complex. The IC50 values against A549 and HepG2 cells were 89.6, 22.6 micromol x L(-1) for baicalin-copper complex, and 138.8, 97.2 micromol x L(-1) for baicalin-aluminium complex. The inhibitory ratio of macrophage on A549 cell was 43.52%, 80.89%, 52.66%, respectively, after the macrophages were stimulated by baicalin, baicalin-copper and baicalin-aluminium complex at a concentration of 160 micromol x L(-1). CONCLUSION: The acute toxicity test in mice showed that the complex was nontoxic to mice. Baicalin-copper complex showed the highest antimicrobial, anti-tumor activity, and the strongest effect on the anti-tumor activity of macrophage, while baicalin showed the lowest activities compared with baicalin-copper and baicalin-aluminium complex.

[Effect of danshensu on JNK and NF-kappaB signal transduction of rat hepatic stellate cells induced by interleukin-1beta].

OBJECTIVE: To investigate the inhibitory effect of danshensu on c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-kappaB) signaling in activated rat hepatic stellate cells (HSCs) and explore the mechanisms of danshensu for inhibiting hepatic fibrosis. METHODS: MTT colorimetric assay was used to detect the proliferation of rat HSCs treated with danshensu, and the apoptosis of the cells was analyzed with Annexin- V-FITC/PI and AO/EB staining. The expressions of P-IkappaB-alpha, NF-kappaBP65 and JNK in HSCs stimulated by IL-1beta with subsequent danshensu treatment were observed by Western blotting. Type III collagen in the medium of HSCs was detected by ELISA and immunocytochemistry. RESULTS AND CONCLUSIONS: Danshensu inhibited the activation and proliferation of HSCs, and increased the apoptotic rate of HSCs and reduced the synthesis and secretion of type III collagen. Danshensu showed obvious inhibitory effect on JNK and P-IkappaB-alpha phosphorylation and NF-kappaBP65 expression in HSCs stimulated by IL-1beta. The mechanism of the actions of dansgensu may be mediated by inhibition of JNK and NF-kappaB signal transduction.