Ethnobotanical study on medicinal plants used by the Yi people in Xiaoliangshan, Yunnan Province, SW China.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yi people in the Xiaoliangshan region in southwest China have a unique practice of combining ritual treatment and traditional medicine to care for patients. Despite increasing urbanization in the area, they have managed to preserve their distinctive lifestyle and extensive knowledge of traditional medicinal plants, setting them apart from other regions. However, there is a lack of systematic documentation on the knowledge of traditional medicinal plants used by the Yi people in Xiaoliangshan. AIM OF THE STUDY: This research aims to achieve the following objectives: 1. Document the diversity of medicinal plants used by the Yi people and explore their therapeutic usages. 2. Evaluate and analyze the main types of diseases with a high incidence in the local area and identify the types of medicinal plants used to treat these diseases. 3. Explore the underlying geographical and human factors influencing both disease prevalence and medicinal plant usage. METHODS: Ethnobotanical research methods were used to record and analyze the medicinal plants used by the Yi in Xiaoliangshan. Experts identified all plant specimens collected during ethnobotanical field surveys. The types of diseases treated by medicinal plants were classified according to the International Classification of Primary Care -2nd. RESULTS: A total of 125 medicinal plants were recorded after interviewing 193 participants. Of the medicinal plants identified, those with over 100 use reports were Paris polyphylla (202 use reports), Taxillus sutchuenensis (183), Artemisia indica (149), and Papaver somniferum (113). A total of 14 disease categories were recorded, with those related to the following categories having higher Informant Consensus factor values (ICF ≥0.85): Pregnancy, Childbearing, Family Planning, General and Unspecified, Urological, Respiratory, Musculoskeletal, and Skin. The highest quantity of medicinal plants is utilized to improve specific diseases and health problems, namely those related to Digestion, Skin, and Musculoskeletal. Fewer plant species were utilized for diseases or health issues associated with Eyes, Psychological, or Pregnancy, Childbearing, and Family Planning. The use reports from the informants also revealed how some medicinal plants are used to treat a variety of diseases or health issues. For instance, Malva pusilla is used for inducing abortion, treating postpartum hemorrhage, and joint sprains; Artemisia indica is used for treating malaria; Argentina lineata is used to remedy tuberculosis and malaria. Taxillus sutchuenensis is used for dealing with cold, pneumonia, and other ailments. CONCLUSIONS: The Yi people in Xiaoliangshan have a rich knowledge of traditional medicinal plants. Decoction and wine brewing are the most common processing methods used for these plants, which are utilized to treat a wide range of diseases. The characteristics of the medicinal use of the Yi people reflects the alpine mountainous environment in which they live, and their medical practices are closely related to traditional healing culture. This study enhances our understanding of the Yi traditional medicine via documentation and offers a valuable reference for future research and the development of new drugs.

High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer: A single-center study.

BACKGROUND: The prognostic assessment of patients after surgical resection of gastric cancer (GC) patients is critical. However, the role of the circadian clock gene NPAS2 expression in GC remains unknown. AIM: To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis. METHODS: The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve, the ROC area under the curve, the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient. RESULTS: Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with tumor-node-metastasis (TNM) stage (P < 0.05), pN stage (P < 0.05), metastasis (P < 0.05), venous invasion (P < 0.05), lymphatic invasion (P < 0.05), and lymph node positive (P < 0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P < 0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P = 0.009), metastasis (P = 0.009), and NPAS2 expression (P = 0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95%CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P < 0.0001). CONCLUSION: NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.

NPM1 is a diagnostic and prognostic biomarker associated with the clinicopathological characteristics of gastric cancer.

NPM1 plays an important role in the occurrence and development of leukemia and various solid tumors. This study aimed to investigate the expression of NPM1 in gastric cancer (GC) and adjacent normal tissues, study the relationship between NPM1 expression and clinicopathological characteristics in GC patients, and explore the impact of NPM1 expression on the diagnosis and prognosis of GC. We used tissue microarray immunohistochemical analysis to examine the expression level of NPM1 in GC and adjacent tissues and analyzed the relationship between NPM1 expression, clinicopathological factors, and GC prognosis. Prognostic values of NPM1 mRNA were also investigated using an online database. qRT-PCR was used to detect the expression of NPM1 mRNA in cancer and adjacent tissues. According to microarray immunohistochemical analysis and qRT-PCR results, NPM1 had a high expression in all adjacent normal tissues. Microarray immunohistochemical analyses demonstrated that the NPM1 was lowly expressed in 75.5% of GC tissues but highly expressed in 24.5% of GC tissues. qRT-PCR results showed NPM1 mRNA low expression in most GC tissues. NPM1 high expression group was associated with a better overall survival rate and disease-free survival rate than the NPM1 low expression group (p<0.01). This result is consistent with that of the online database. The receiver operating characteristics curve showed that NPM1 was valuable in the diagnosis of GC. The assessment of NPM1 expression in GC samples may represent a useful tool for GC diagnosis and prognosis assessment.

Esmolol inhibits inflammation and apoptosis in the intestinal tissue via the overexpression of NF-κB-p65 in the early stage sepsis rats.

BACKGROUND/AIMS: Accumulating evidence reveals esmolol could protect the gut mucosa through the regulation of immune response and inflammation in patients with sepsis. However, its underlying mechanism is not fully understood. MATERIALS AND METHODS: Diamine oxidase (DAO), intestinal fatty acid-binding protein (I-FABP), interleukin (IL)-6, and IL-10 in the plasma of rats were detected by ELISA assay. Western blotting was utilized to measure the expression levels of NF-kappa B-p65, Bcl-2, and cleaved caspase-3 in the intestinal tissues. The survival analysis was performed in each group. RESULTS: The plasma levels of DAO and IL-10 levels were increased, whereas that of I-FABP and IL-6 were decreased in the sepsis rats after esmolol treatment, indicating that after the esmolol treatment, the intestinal inflammation and damages were remarkably reduced as compared to those in the normal saline treated sepsis rats. NF-κB-p65 and Bcl-2 were highly expressed, but cleaved caspase-3 showed lower expression in the esmolol treated groups. However, at the same time, we observed contrasting results in the normal saline treated group. Western blotting data indicated that the esmolol treatment inhibited the inflammation and apoptosis in the intestinal tissue due to the overexpression of NF-κB-p65 in the celiac sepsis rats. The survival analysis results indicate that the esmolol infusion should be used in the early stages sepsis rats. CONCLUSION: Esmolol can suppress inflammation and apoptosis in the intestinal tissue via the overexpression of NF-kappa B-p65 in the early stage sepsis rats. kappa BEarly-stage use of esmolol might be an ideal treatment method for sepsis.

Identification of key candidate genes and pathways in anaplastic thyroid cancer by bioinformatics analysis.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a refractory and poor prognosis tumor Present study aimed to investigate the underlying biological functions and pathways involved in the development of ATC and to identify potential hub genes and candidate biomarkers of ATC. MATERIALS AND METHODS: Bioinformatics analyses were performed to identify the differentially expressed genes (DEGs) between ATC tissue samples and adjacent normal tissue samples. Protein-protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape software and divided into sub-networks using the Molecular Complex Detection (MCODE) plug-in. DEGs in each module was analyzed by enrichment analysis of the KEGG Orthology Based Annotation System (KOBAS) web software version 3.0. Eventually, the hub genes from bioinformatics analysis were verified by qRT-PCR assay in different ATC cell lines. RESULTS: Thirty hub genes were selected and three modules were built by the Cytoscape software from the PPI network. Seven genes (CDK1, CCNB2, BUB1B, CDC20, RRM2, CHEK1 and CDC45) were screened from thirty hub genes. Enrichment analysis showed that these hub genes were primarily accumulated in 'cell cycle', 'p53 signaling pathway', 'viral carcinogenesis', 'pyrimidine metabolism' and 'ubiquitin mediated proteolysis'. The results of qRT-PCR indicated that seven hub genes were unregulated in three ATC cell lines compared with normal thyroid gland cell. CONCLUSIONS: These findings suggest that CDK1, CCNB2, BUB1B, CDC20, RRM2, CHEK1 and CDC45 may serve as novel diagnosis biomarkers and potential therapeutic target for ATC.

Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer.

BACKGROUND: Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown. METHODS: We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development. RESULTS: AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC. CONCLUSIONS: AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC.

Systematic assessment of complications after robotic-assisted total versus distal gastrectomy for advanced gastric cancer: A retrospective propensity score-matched study using Clavien-Dindo classification.

BACKGROUND: Despite increasing evidence demonstrated robot-assisted distal gastrectomy (RADG) is safe and feasible for the treatment of advanced gastric cancer (AGC), robot-assisted total gastrectomy (RATG) remains a challenging procedure due to its technical difficulties and possible postoperative complications (POCs). This study aimed to systematically evaluate POCs following RATG. METHODS: Between January 2017 and January 2019, 319 AGC patients with pathological stage T2-4aN0-3M0 who underwent RADG or RATG were enrolled. POCs were stratified using the Clavien-Dindo classification. One-to-one propensity score matching was performed to reduce confounding differences. RESULTS: After matching, 266 patients met the criteria for further analysis. Ultimately, 64 patients (24.1%) who developed POCs had 126 clinical manifestation events. Overall the POCs rate was significantly greater after RATG in comparison with RADG (29.3% vs. 18.8%; P = 0.045), and more major POCs (Clavien-Dindo grade ≥ IIIa) were observed in the RATG group (14.3% vs. 5.3%; P = 0.013). The POCs were then classified into local and systemic POCs. The rates of local POCs (35.3% vs. 19.5%; P = 0.004) and systemic POCs (24.8% vs. 15.0%; P = 0.046) were significantly higher in the RATG group than the RADG group. Subgroup analysis showed that the anastomotic leakage rate was higher after RATG (5.3% vs. 0.8%; P = 0.031), whereas the remaining POCs were similar between the two groups. Patients with higher POCs significantly had longer postoperative length of stay (R = 0.895, P = 0.003). Multivariate analysis confirmed age, extent of resection, and TNM stage were risk factors for all POCs. CONCLUSIONS: These findings demonstrated that RATG is technically feasible and safe for treatment of AGC with acceptable morbidity and mortality rates. The POCs rate of RATG was higher than RADG, especially for anastomotic leakage. More effective anastomotic techniques are needed in RATG to prevent leakage.

Long non-coding RNA CASC19 is associated with the progression and prognosis of advanced gastric cancer.

Evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) are involved in the development and progression of advanced gastric cancer (AGC). Using RNA sequencing data and clinical information obtained from The Cancer Gene Atlas, we combined differential lncRNA expression profiling and weighted gene co-expression network analysis to identify key lncRNAs associated with AGC progression and prognosis. Cancer susceptibility 19 (CASC19) was the top hub lncRNA among the lncRNAs included in the gene module most significantly correlated with AGC's pathological variables. CASC19 was upregulated in AGC clinical samples and was significantly associated with higher pathologic TNM stage, pathologic T stage, lymph node metastasis, and poor overall survival. Multivariable Cox analysis confirmed that CASC19 overexpression is an independent prognostic factor for overall survival. Furthermore, quantitative real-time PCR assay confirmed that CASC19 expression in four human gastric cancer cells (AGS, BGC-823, MGC-803, and HGC-27) was significantly upregulated compared with human normal gastric mucosal epithelial cell line (GES-1). Functionally, CASC19 knockdown inhibited GC cell proliferation and migration in vitro. These findings suggest that CASC19 may be a novel prognostic biomarker and a potential therapeutic target for AGC.

Interleukin-6 derived from cutaneous deficiency of stearoyl-CoA desaturase- 1 may mediate metabolic organ crosstalk among skin, adipose tissue and liver.

Stearoyl-CoA desaturase 1 (SCD1), a lipogenic enzyme that adds a double bond at the delta 9 position of stearate (C18: 0) and palmitate (C16: 0), has been proven to be important in the development of obesity. Mice with skin-specific deficiency of SCD1 (SKO) display increased whole-body energy expenditure, which is protective against adiposity from a high-fat diet because it improves glucose clearance, insulin sensitivity, and hepatic steatosis. Of note, these mice also display elevated levels of the "pro-inflammatory" plasma interleukin-6 (IL-6). In whole skin of SKO mice, IL-6 mRNA levels are increased, and protein expression is evident in hair follicle cells and in keratinocytes. Recently, the well-known role of IL-6 in causing white adipose tissue lipolysis has been linked to indirectly activating the gluconeogenic enzyme pyruvate carboxylase 1 in the liver, thereby increasing hepatic glucose production. In this study, we suggest that skin-derived IL-6 leads to white adipose tissue lipolysis, which contributes to the lean phenotype of SKO mice without the incidence of meta-inflammation that is associated with IL-6 signaling.

Severity and incidence of complications assessed by the Clavien-Dindo classification following robotic and laparoscopic gastrectomy for advanced gastric cancer: a retrospective and propensity score-matched study.

BACKGROUND: Robot-assisted gastrectomy (RAG) has been increasingly used for the treatment of advanced gastric cancer (AGC), and many advantages over laparoscopy-assisted gastrectomy (LAG) have been reported. However, its postgastrectomy complications still under investigation and the results remain controversial. This study aimed to objectively assess the incidence and severity of complications following RAG vs. LAG using Clavien-Dindo (C-D) classification and to identify risk factors related to complications. METHODS: Five hundred and twenty-seven patients with AGC who underwent RAG or LAG between January 2016 and May 2018 were enrolled in this study. Complications were categorized according to the C-D classification. The complications following RAG and LAG were compared using one-to-one propensity score matching (PSM) analysis and subgroup analyses. Logistic regression analyses were performed to identify risk factors related to complications. RESULTS: RAG was performed in 251 patients (47.6%) and LAG in 276 patients (52.4%). Before PSM, the RAG group had a smaller tumour size (P = 0.004) and less patients with previous abdominal operation (P = 0.013). After PSM, a well-balanced cohort of 446 patients (223 in each group) was further analyzed. Of interest, the incidence of overall and severe complications (C-D grade ≥ IIIa) following the RAG group were significantly fewer than the LAG group (overall, 24.5% vs. 18.8%, P < 0.001; severe, 8.9% vs. 17.5%, P = 0.002). Subgroup analyses showed statistically significant difference were also observed in most stratified parameters. Multivariable analysis identified age ≥ 65 years, total gastrectomy, stage T3-T4a, stage II-III, and operation time ≥ 250 min as independent predictors of overall complications. Additionally, age ≥ 65 years, stage II-III, and operation time ≥ 250 min were confirmed as independent risk factors for severe complications. CONCLUSIONS: RAG with D2 lymphadenectomy is feasible and safe for the treatment of AGC in terms of the lower incidence and severity of complications.

Rifampin suppresses osteoclastogenesis and titanium particle-induced osteolysis via modulating RANKL signaling pathways.

Wear particles liberated from the surface of prostheses are considered to be main reason for osteoclast bone resorption and that extensive osteoclastogenesis leads to peri-implant osteolysis and subsequent prosthetic loosening. The aim of this study was to assess the effect of rifampin on osteoclastogenesis and titanium (Ti) particle-induced osteolysis. The Ti particle-induced osteolysis mouse calvarial model and bone marrow-derived macrophages (BMMs) were used. Rifampin, at dose of 10 or 50 mg/kg/day, was respectively given intraperitoneally for 14 days in vivo. The calvariae were removed and processed for Further histological analysis. In vitro, osteoclasts were generated from mouse BMMs with receptor activator of nuclear factor-κB ligand (RANKL) and the macrophage colony stimulating factor. Rifampin at different concentrations was added to the medium. The cell viability, tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity and resorption on bone slices were analysis. Osteoclast-specific genes and RANKL-induced MAPKs signaling were tested for further study of the mechanism. Rifampin inhibited Ti-induced osteolysis and osteoclastogenesis in vivo. In vitro data indicated that rifampin suppressed osteoclast differentiation and bone resorption in a dose-dependent manner. Moreover, rifampin significantly reduced the expression of osteoclast-specific markers, including TRAP, cathepsin K, V-ATPase d2, V-ATPase a3, c-Fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that rifampin inhibited osteoclast formation by specifically abrogating RANKL-induced p38 and NF-κB signaling. Rifampin had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.

Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical for Lymphatic Vascular Development and Function.

The molecular mechanisms underlying lymphatic vascular development and function are not well understood. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and atherosclerosis. Here, we show that constitutive loss of EC Map4k4 in mice causes postnatal lethality due to chylothorax, suggesting that Map4k4 is required for normal lymphatic vascular function. Mice constitutively lacking EC Map4k4 displayed dilated lymphatic capillaries, insufficient lymphatic valves, and impaired lymphatic flow; furthermore, primary ECs derived from these animals displayed enhanced proliferation compared with controls. Yeast 2-hybrid analyses identified the Ras GTPase-activating protein Rasa1, a known regulator of lymphatic development and lymphatic endothelial cell fate, as a direct interacting partner for Map4k4. Map4k4 silencing in ECs enhanced basal Ras and extracellular signal-regulated kinase (Erk) activities, and primary ECs lacking Map4k4 displayed enhanced lymphatic EC marker expression. Taken together, these results reveal that EC Map4k4 is critical for lymphatic vascular development by regulating EC quiescence and lymphatic EC fate.

Clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation: a meta-analysis of seven case-control studies.

The purpose of this study was to evaluate the clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation. We searched the PubMed, Embase and Web of Science databases and included all case-control trials that reported on the clinical outcomes of osteonecrosis progression, incidence of total hip arthroplasty and improvement in Harris hip scores. Overall, seven case-control trials were included. Compared with the controls, patients treated with the bone marrow stem cells implantation treatment showed improved clinical outcomes with delayed osteonecrosis progression (odds ratio = 0.17, 95% CI: 0.09 - 0.32; p <0.001), a lower total hip arthroplasty incidence (odds ratio = 0.30, 95% CI: 0.12 - 0.72; p <0.01) and increased Harris hip scores (mean difference = 4.76, 95% CI: 1.24 - 8.28; p<0.01). The heterogeneity, publication bias, and sensitivity analyses showed no statistical difference significant differences between studies. Thus, our study suggests that autologous bone marrow stem cells implantation has a good therapeutic effect on osteonecrosis of the femoral, resulting in beneficial clinical outcomes. However, trials with larger sample sizes are needed to confirm these findings.

Clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation: a meta-analysis of seven case-control studies

The purpose of this study was to evaluate the clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation. We searched the PubMed, Embase and Web of Science databases and included all case-control trials that reported on the clinical outcomes of osteonecrosis progression, incidence of total hip arthroplasty and improvement in Harris hip scores. Overall, seven case-control trials were included. Compared with the controls, patients treated with the bone marrow stem cells implantation treatment showed improved clinical outcomes with delayed osteonecrosis progression (odds ratio = 0.17, 95% CI: 0.09 - 0.32; p <0.001), a lower total hip arthroplasty incidence (odds ratio = 0.30, 95% CI: 0.12 - 0.72; p <0.01) and increased Harris hip scores (mean difference = 4.76, 95% CI: 1.24 - 8.28; p<0.01). The heterogeneity, publication bias, and sensitivity analyses showed no statistical difference significant differences between studies. Thus, our study suggests that autologous bone marrow stem cells implantation has a good therapeutic effect on osteonecrosis of the femoral, resulting in beneficial clinical outcomes. However, trials with larger sample sizes are needed to confirm these findings.

Involvement of MicroRNA-210 Demethylation in Steroid-associated Osteonecrosis of the Femoral Head.

Angiogenesis is an important event in steroid-associated osteonecrosis of the femoral head (SONFH). Here we performed miRNA microarray with SONFH tissues (ONs) and the adjacent normal tissues (NLs) to select the angiogenic miRNA. The results showed that miR-210 was differentially expressed in SONFH versus normal tissues. Unexpectedly, its specific transcription factor, hypoxia-inducible factor-1α, was shown of no significant changes in ONs compared with NLs. Further Bisulfite sequencing revealed that miR-210 is embedded in a CpG island and miR-210 gene has 2 CpG sites with lower methylation percentage in ONs compared with NLs. Additionally, ONs with lower miR-210 gene methylation exhibited higher miR-210 expression. Next, we found that the endothelial cells treated with demethylating agents could significantly increase the expression of miR-210, along with promoted cell viability and differentiation. Some angiogenic genes (VEGF, bFGF, TNF-α and PCNA) were up-regulated as well. In addition, the supernatant of the cells after demethylation treatment displayed an enhanced ability of recruiting new microvessels in vivo. Taken together, our study not only provides novel insights into the regulation of angiogenesis in this disease, but also reveals a therapeutic opportunity for treatment of SONFH patients with demethylating agents.

Role of mimic of manganese superoxide dismutase in proliferation and apoptosis of gastric carcinoma BGC-823 cells in vitro and in vivo.

The aim of this study was to investigate the anti-cancer effect and mechanism of mimic of manganese superoxide dismutase (MnSODm) in gastric carcinoma cells in vitro and in vivo. The MTT was used to measure cytotoxicity of the MnSODm. The appearance of apoptotic BGC-823 cells was detected by flow cytometry analysis. Apoptosis proteins, caspase family and Bcl-2 family were viewed by Western blotting. The phosphoinositide 3 kinase (PI3K)/Akt signaling pathway and the NF-κB pathway were also examined. PI3K inhibitor LY294002 was used to examine the involvement of the PI3K/Akt signaling pathway in this apoptosis-inducing effect. BGC-823 cell xenograft serious combined immunodeficiency disease mice were used for the in vivo study. The result showed that MnSODm could induce growth arrest and apoptosis of BGC-823 cells in vitro and in vivo. Further analysis demonstrated the involvement of activation of caspase cascade in MnSODm induced apoptosis. The expression of anti-apoptotic Bcl-2 was decreased, whereas the expression of pro-apoptotic Bax protein was increased. The main mechanisms on MnSODm-induced apoptosis were related to the inhibition of PI3K expression, which inactivated the phosphorylation of Akt involving the prevention of NF-κB phosphorylation and nuclear translocation. This phenomenon could be inhibited by the PI3K inhibitor LY294002. We demonstrated that the mechanisms of MnSODm inhibited the BGC-823 cell proliferation in vitro primarily are related to the induced apoptosis, which appears to be regulated by the PI3K/Akt pathway involving the prevention of NF-κB nuclear translocation, and then triggering the activation of the caspase cascades. Moreover, the anticancer effect in vivo on BGC-823 cells xenografted mice was also due to MnSODm-mediated apoptosis.

A "two-incision" approach for en bloc resection of periacetabular tumors with illustrations from a cadaver.

A "two-incision" approach for en bloc resection of periacetabular tumors and prosthesis reconstruction is described. The first incision begins in the middle of the iliac crest, continues over the inguinal ligament, extends to the symphysis pubis and then turns down to ischial tuberosity. The muscles attached to the iliac crest are only separated from its internal side. All the attachments of the abductor muscles to the iliac crest are left intact. The second incision runs from the sacroiliac joint to the greater trochanter and is curved in shape, providing external exposure of the sciatic notch and ischial tuberosity. Communication between the two approaches is possible inside and outside under the abductor muscles or through the sciatic notch. En bloc resection of the tumor is performed by cutting the pubic symphysis and iliac as planned preoperatively. The iliac osteotomy is performed by using a Gigli saw that has been led through the sciatic notch and under the abductor muscles. This "two-incision" approach not only provides enough exposure to perform en bloc resection of periacetabular tumors, but also protects the continuity of the abductor muscles between the pelvis and greater trochanter, thus preventing prosthesis dislocation.

CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance.

The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation in adipose tissue and liver. The CD40 receptor and its ligand CD40L initiate immune cell signaling promoting inflammation, but conflicting data on CD40L-null mice confound its role in obesity-associated insulin resistance. Here, we demonstrate that CD40 receptor-deficient mice on a high-fat diet display the expected decrease in hepatic cytokine levels but paradoxically exhibit liver steatosis, insulin resistance, and glucose intolerance compared with their age-matched wild-type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40-null mice compared with wild-type mice. In contrast to liver, adipose tissue in CD40-deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8(+) effector T cells. In addition, ex vivo explants of epididymal adipose tissue from CD40(-/-) mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that 1) CD40-null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate its inflammation in obesity, thereby protecting against hepatic steatosis.

Stat3 upregulates leucine-rich repeat-containing g protein-coupled receptor 4 expression in osteosarcoma cells.

The activation of signal transducer and activator of transcription 3 (Stat3) signaling is the common hallmark in various human cancers including osteosarcoma. In the present study, according to PCR-based microarrays using cDNA prepared from interleukin-6 (IL-6) treated osteosarcoma cells, we found that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) was a transcriptional target of Stat3. Overexpression of Stat3 promoted LGR4 expression, while its deficiency using small interfering RNA (siRNA) reduced LGR4 expression. Furthermore, we identified a Stat3 binding motif located at -556 to -549 bp in the LGR4 promoter that is able to interact with Stat3. Thus, our results suggest a previously unknown Stat3-LGR4 molecular network, which may control osteosarcoma development and progression.

[FAK/c-Src signaling pathway mediates the expression of cell surface HSP90 in cultured human prostate cancer cells and its association with their invasive capability].

OBJECTIVE: To investigate the expression of heat shock protein 90 (HSP90) on the cell surface of highly invasive human prostate cancer cells PC3 and its possible molecular mechanisms of its effect on cell invasion through analyzing FAK/Src signaling pathway. METHODS: The expression of cell surface HSP90 on PC3 cells was studied by immunofluorescence staining and surface biotinylation assay respectively. A specific HSP90 antibody was used to inhibit the cell surface HSP90. In vitro cell invasion was assessed by modified Boyden chambers. Phosphorylated FAK on tyr 397, 576, 577 and 925, and phosphorylated c-Src on tyr 416 were examined by Western blot assay. The association between FAK and c-Src was analyzed by immunoprecipitation. The effects of FAK knockdown by siRNA or Src kinases inhibitor PP2, with or without anti-HSP90 antibody, on PC3 cell invasion were also evaluated. RESULTS: A pool of HSP90 was detected on the cell surface of PC3 cells. A specific HSP90 antibody significantly retarded tumor cell invasion. Concomitant with this finding, targeting cell surface HSP90 significantly inhibited the phosphorylations of FAK and c-Src, and also the interactions between FAK and c-Src. FAK knockdown or PP2 dramatically suppressed cell invasion, however, anti-HSP90 antibody didn't further inhibit cell invasion. CONCLUSIONS: Cell surface HSP90 promotes human prostate cancer cell invasion through a FAK/c-Src signaling, with may be a novel therapeutic target against metastatic tumors.