Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. Osteopontin (OPN) is thought to be closely related to the occurrence, metastasis and prognosis of many types of tumors. AIM: To investigate the effects of OPN on the proliferation, invasion and migration of GC cells and its possible mechanism. METHODS: The mRNA and protein expression of OPN in the GC cells were analyzed by real-time quantitative-reverse transcription polymerase chain reaction and western blotting, and observe the effect of varying degree expression OPN on the proliferation and other behaviors of GC. Next, the effects of OPN knockdown on GC cells migration and invasion were examined. The short hairpin RNA (shRNA) and negative control shRNA targeting OPN-shRNA were transfected into the cells according to the manufacturer's instructions. Non transfected cells were classified as control in the identical transfecting process. 24 h after RNA transfection cell proliferation activity was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay, and cell invasiveness and migration were detected by Trans well assay. Meanwhile, the expression of protein kinase B (AKT), matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) in the human GC cell lines was detected by reverse transcription polymerase chain reaction and western blotting. RESULTS: The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells. OPN knockdown by specific shRNA noticeably reduced the capabilities of proliferation, invasion and migration of SGC-7901 cells. Moreover, in the experiments of investigating the underlying mechanism, results showed that OPN knockdown could down-regulated the expression of MMP-2 and VEGF, it also decreased the phosphorylation of AKT. Meanwhile, the protein expression levels of MMP-2, VEGF and phosphorylated AKT was noticeable lower than that in control group in the GC cells after they were added to phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002). CONCLUSION: These results suggested that OPN though PI3K/AKT/mammalian target of rapamycin signal pathway to up-regulate MMP-2 and VEGF expression, which contribute SGC-7901 cells to proliferation, invasion and migration. Thus, our results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.

A novel risk model for predicting early relapse in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem-cell transplantation.

Relapse remains the leading cause of death in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem-cell transplantation (allo-HSCT), limiting the efficacy of allo-HSCT. Thus, the ability to identify high-risk patients in a manner that permits early intervention has the potential to improve survival outcomes. We retrospectively enrolled 414 younger patients (aged 14-60 years) with AML who received allo-HSCT between January 2014 and May 2020. From June 2020 to June 2021, 110 consecutive patients were included prospectively in the validation cohort. The primary outcome was early relapse (relapse within 1 year). The cumulative incidence of early relapse after allo-HSCT was 11.8%. The overall survival rate for patients who relapsed within 1-year was 4.1% at 3 years after relapse. After multivariable adjustment, statistically significant associations between primary resistance, pre-transplantation measurable residual disease, DNMT3A mutation, or white blood cell count at diagnosis and early relapse were observed. An early relapse prediction model was developed based on these factors and the model performed well. Patients deemed to have a high risk or a low risk of early relapse had early relapse rates of 26.2% and 6.8%, respectively (P < 0.001). The prediction model could be used to help identify patients at risk for early relapse and to guide personalized relapse prevention.

[Effect of modified holmium laser enucleation of the prostate on postoperative urinary control and sexual function in elderly patients with benign prostatic hyperplasia].

OBJECTIVE: To investigate the impact of retaining part of the urethral mucosa on postoperative urinary control, erectile function, and ejaculatory function in patients undergoing holmium laser enucleation of the prostate (HoLEP) surgery. METHODS: A retrospective analysis was conducted on 176 benign prostatic hyperplasia (BPH) patients who underwent surgical treatment at our hospital from January 2019 to January 2022, including 80 cases of modified HoLEP surgery and 96 cases of standard HoLEP surgery. Preoperative and postoperative clinical data were collected and analyzed. RESULTS: At 3 months postoperatively, both groups showed significant improvement in maximum flow rate (Qmax), International Prostate Symptom Score (IPSS) , residual urine volume (RUV) , and quality of life (QOL) compared to pre-treatment values, with statistically significant differences (P<0.05) . There was a significant difference in QOL scores between the experimental and control groups (P<0.05) . At 3 months postoperatively, the incidence of urinary incontinence was significantly lower in the experimental group compared to the control group (P<0.05) . At 6 months postoperatively, both groups showed a significant increase in International Index of Erectile Function-5 (IIEF-5) scores compared to preoperative values (P<0.05) , with no significant difference between the two groups. The incidence of retrograde ejaculation in the experimental group was significantly lower than that in the control group (P<0.05) . CONCLUSIONS: Retaining part of the urethral mucosa in HoLEP surgery can effectively treat BPH, providing significant advantages in terms of urinary control and playing a positive role in overall postoperative sexual function recovery.

A Ratiometric Fiber Optic Sensor Based on CdTe QDs Functionalized with Glutathione and Mercaptopropionic Acid for On-Site Monitoring of Antibiotic Ciprofloxacin in Aquaculture Water.

A ratiometric fluorescence fiber-optical sensor system (RFFS) merging a Y-type optical fiber spectrometer and CdTe QDs composite functionalized with glutathione and mercaptopropionic acid (GMPA@CdTe-QDs) for highly selective and on-site detection of ciprofloxacin (CIP) in environmental water samples was designed. Our preliminary results suggested that the red fluorescence of the synthesized GMPA@CdTe-QDs was effectively quenched by CIP. Based on this, the RFFS/GMPA@CdTe-QDs system was successfully fabricated and used for highly selective and rapid detection of CIP on site in the concentration range from 0 to 45 µM with the detection limit of 0.90 µM. The established method exhibited good interference resistance to the analogues of CIP and provided a great potential platform for real-time detection of CIP residues in environmental water. In addition, the fluorescence quenching mechanism of GMPA@CdTe-QDs by CIP was also investigated by means of temperature effect, fluorescence lifetime, ultraviolet (UV) visible absorption, and fluorescent spectra. Our results suggested clearly that the red fluorescence of GMPA@CdTe-QDs was quenched by CIP via the photoinduced electron-transfer (PET) mode.

National Nutrition and Health Systematic Survey for Children 0-17 Years of Age in China.

The main purpose of the National Nutrition and Health Systematic Survey for children 0-17 years of age in China (CNHSC) was to collect basic data on the nutrition, development, and health status for children in different regions across China using evidence-based, reliable, and cost-effective approaches. Children and their parents or guardians from seven regions (south, southwest, north, northwest, eastern, central, and northeast China) in China were recruited. A multi-stage stratified randomized sampling method was used. Two provinces were randomly sampled from each of the seven regions, from which one urban district and one rural country were also randomly sampled, resulting in a total of 28 survey counties/districts. Dietary surveys, health examinations, laboratory testing, and questionnaires were used to collect dietary intake, nutritional status, child development, and health status information. Nutrition, health, and lifestyle assessment of children and their parents was determined using the Knowledge Attitude Practice (KAP) survey. Greater than 100,000 children (38,000 children < 6 years of age and 66,000 children 6-17 years of age) completed the survey. The survey provided comprehensive data on child nutrition and health status for future studies and will serve as the basis for an integrated nutrition and health improvement strategies proposal for children in China.

Preemptive low-dose interleukin-2 or DLI for late-onset minimal residual disease in acute leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.

Minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) heralds high risk of relapse. Whether preemptive recombinant interleukin-2 (pre-IL2) is effective for patients with late-onset MRD (LMRD) remains unknown. We retrospectively compared the efficacy and safety of pre-IL2 (n = 30) and pre-DLI (n = 25) for LMRD in patients receiving allo-HSCT for acute leukemia or myelodysplastic syndrome. The 1-year overall survival (OS) and disease-free survival (DFS) rates were 86.7% and 78.4% (P = 0.267), 83.3% and 75.6% (P = 0.329), the cumulative incidence of grades III-IV acute graft-versus-host disease (aGVHD) at 100 days post-preemptive intervention was 3.3% and 12.0% (P = 0.226) in the pre-IL2 group and pre-DLI group, respectively. The 1-year cumulative incidence of moderate/severe chronic GVHD (cGVHD), relapse (CIR), and non-relapse mortality (NRM) were 7.7% and 27.9% (P = 0.018), 13.6% and 20.0% (P = 0.561) and 3.3% and 5.5% (P = 0.321) in the two groups, respectively. No remarkable differences in CIR, OS, and DFS between the two intervention groups were found in multivariate analysis. The GVHD-free and relapse-free survival (GRFS) were better in the pre-IL2 group than in the pre-DLI group (HR = 0.31, 95% confidence interval (CI), 0.12-0.76; P = 0.011). In conclusion, preemptive low-dose IL2 and preemptive DLI yield comparable outcomes for patients with LMRD receiving allo-HSCT, in terms of aGVHD, NRM, relapse, OS, and DFS. However, preemptive low-dose IL2 has a lower incidence of moderate/severe cGVHD and a higher CRFS. Preemptive low-dose IL2 may be an alternative method for patients who develop LMRD after allo-HSCT, particularly for patients who cannot receive preemptive DLI.

Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic ß-Cell Growth and Insulin Secretion.

In the past 15 years, gut microbiota emerged as a crucial player in health and disease. Enormous progress was made in the analysis of its composition, even in the discovery of novel species. It is time to go beyond mere microbiota-disease associations and, instead, provide more causal analyses. A key mechanism of metabolic regulation by the gut microbiota is through the production of short-chain fatty acids (SCFAs). Acting as supplemental nutrients and specific ligands of two G-protein-coupled receptors (GPCRs), they target the intestines, brain, liver, and adipose tissue, and they regulate appetite, energy expenditure, adiposity, and glucose production. With accumulating but sometimes conflicting research results, key questions emerged. Do SCFAs regulate pancreatic islets directly? What is the effect of ß-cell-specific receptor deletions? What are the mechanisms used by SCFAs to regulate ß-cell proliferation, survival, and secretion? The receptors FFA2/3 are normally expressed on pancreatic ß-cells. Deficiency in FFA2 may have caused glucose intolerance and ß-cell deficiency in mice. However, this was contrasted by a double-receptor knockout. Even more controversial are the effects of SCFAs on insulin secretion; there might be no direct effect at all. Unable to draw clear conclusions, this review reveals some of the recent controversies.

Clinical Effects of CpG-Based Treatment on the Efficacy of Hepatocellular Carcinoma by Skewing Polarization Toward M1 Macrophage from M2.

OBJECTIVE: This study aims to explore the clinical efficacy of CpG-based therapy for treating hepatocellular carcinoma (HCC) by skewing polarization toward M1 macrophage from M2. METHODS: Pulmonary metastasis rate, overall survival time, and remission rate of 10 patients with HCC treated with transcatheter arterial chemoembolization (TACE) combined with CpG therapy and 10 age-, gender-, and TNM0-matched patients treated with TACE (control group) were compared. RESULTS: No pulmonary metastasis rate was 70% in the combined treatment group and 40% in the control group, respectively; and the differences between the two groups were statistically significant (p < 0.05). Median overall survival time was 22 months in the combined treatment group, compared with 6.65 months in the control group (p < 0.05). Remission rate in the combined treatment group (70%) was higher than in the control group (30%), but the differences between these two groups were not statistically significant (p > 0.05). CONCLUSION: Compared with TACE, CpG combined with TACE can decrease the pulmonary metastasis rate. This combined therapy can also improve the overall survival time of patients.

Tumor necrosis factor alpha-238G/A polymorphism and risk of breast cancer: An update by meta-analysis.

BACKGROUND: The association between the tumor necrosis factor-alpha gene (TNF-a) -238G/A polymorphism and the breast cancer has been analyzed in several studies, but the results have been inconclusive. We then performed a meta-analysis to get a precise estimation of the association. METHODS: Eight case-control studies with a total of 37,257 cases and 39,564 controls were identified by searching the ISI Web of Knowledge database and the PubMed database up to August 2014. RESULTS: Overall, no association was found between TNF-alpha-238G/A polymorphism and breast cancer in any of genetic model (additive model OR = 1.06, 95%CI: 0.94-1.21, Pheterogeneity = .02; homozygous model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98; dominant model OR = 1.06, 95%CI: 0.92-1.21, Pheterogeneity = .01; recessive model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98). Furthermore, no significant association was identified when stratified by ethnicity (Caucasian, Asian). CONCLUSION: This meta-analysis indicated that the TNF-alpha-238G/A polymorphism is not associated with breast cancer risk in the overall population.

Inhibitory effects of tanshinones towards the catalytic activity of UDP-glucuronosyltransferases (UGTs).

CONTENTS: Danshen is a popular herb employed to treat cardiovascular and cerebrovascular diseases worldwide. Danshen-drug interaction has not been well studied. OBJECTIVE: The inhibitory effects of four major tanshinones (tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone I) on UDP-glucuronosyltransferases (UGTs) isoforms were determined to better understand the mechanism of danshen-prescription drugs interaction. MATERIALS AND METHODS: In vitro recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed. Tanshinones (100 µM) was used to perform the initial screening of inhibition capability. High-performance liquid chromatography (HPLC) was used to separate 4-MU and its glucuronide. In vitro-in vivo extrapolation (IV-IVE) was employed to predict in vivo inhibition situation. RESULTS: Cryptotanshinone inhibited UGT1A7 and UGT1A9 with IC50 values of 1.91 ± 0.27 and 0.27 ± 0.03 µM, respectively. Dihydrotanshinone I inhibited UGT1A9-catalyzed 4-MU glucuronidation reaction with the IC50 value of 0.72 ± 0.04 µM. The inhibition of cryptotanshinone towards UGT1A7 and UGT1A9 was best fit to competitive inhibition type, and UGT1A9 was non-competitively inhibited by dihydrotanshinone I. Using in vitro inhibition kinetic parameters (Ki) and in vivo maximum plasma concentration (Cmax) of cryptotanshinone and dihydrotanshinone I, the change of area-under-the-concentration-time curve (AUC) was predicted to be 0.4-4.2%, 3.7-56.3%, and 0.6-6.4% induced by cryptotanshinone and dihydrotanshinone inhibition towards UGT1A7 and UGT1A9, respectively. DISCUSSION AND CONCLUSION: The inhibitory effects of tanshinones towards important UGT isoforms were evaluated in the present study, which provide helpful information for exploring the mechanism of danshen-clinical drugs interaction.

350-560 µm gelatin sponge particles combined with transcatheter arterial chemoembolization for the treatment of elderly hepatocellular carcinoma: The safety and efficacy.

To retrospectively analyze the safety and efficacy of 350-560 µm gelatin sponge particles combined with single-chemotherapy drug transcatheter arterial chemoembolization (Gs-TACE) for the treatment of elderly hepatocellular carcinoma without surgical resection.Thirty elderly hepatocellular carcinoma patients without surgical resection, who received Gs-TACE in our hospital, were selected. Slowly injected gelatin sponge particles (350-560 µm)+ 10 mg lobaplatin injection into the regional embolization tumor target vessel. The Response Evaluation Criteria for Solid Tumors could be used to evaluate the tumor response after intervention surgery.Eighty-nine times of intervention TACE were conducted on the 30 patients. The average size of tumor was 8.3 cm. The median survival time was 28 months, and the 1 and 2-year survival rates were 89% and 58%, respectively. The Response Evaluation Criteria for Solid Tumors was used to evaluate the tumor response, and found that the complete response, partial response, and OR were 30%, 56.67%, and 86.67%, respectively, at 1 month after intervention surgery. The patients were divided into groups: 60 to 65 years age group (A), >65 to 75 years age group (B), and >75 years age group (C); the median survival times were 16, 32, and 33 months, respectively, and there was statistical difference between A group, B group, and C group. The analysis of prognosis factors showed that there was statistical significance in age, Barcelona Clinic Liver Cancer stage, portal vein invasion, and alpha fetal protein (AFP), and age was the protective factor.Gelatin sponge particles (350-560 µm), combined with transcatheter arterial chemoembolization, provide an alternative method for the treatment of elderly hepatocellular carcinoma without surgical resection.

Effects of Sishen Pills on Ghrelin-CaM-MLCK Signaling Pathway in Sinuses Ventriculi of Rats with Diarrhea of Yang Deficieney of Spleen and Kidney / 中国中医药信息杂志

Objective To explore the effects of Sishen Pills on Ghrelin-CaM-MLCK signaling pathway with sinuses ventriculi in diarrhea rats of yang deficieney of spleen and kidney; To discuss its mechanism of action. Methods A model rats with diarrhea model of yang deficieney of spleen and kidney was established by treated with intragastric administration of adenine and Senna water decoction to replicate. 72 SD rats were randomly divided into normal group, model group, positive medicine group, Sishen Pills high-, medium- and low-dose groups, with 12 rats in each group. Each medication group was given relevant medicine for gavage, for 14 days. Immunohistochemistry and Western blot were used to detect the expressions of Ghrelin and GHSR, CaM, and MLCK protein in the sinuses ventriculi. Results In the model group, Ghrelin, GHSR, CaM and MLCK protein expressions of the sinuses ventriculi significantly increased (P<0.01). In each medication group, protein expression of the indexes was lower than the model group (P<0.05, P<0.01). The Sishen Pills high-dose group was particularly obvious. Conclusion The effect of Sishen Pills on diarrhea model rats of yang deficieney of spleen and kidney may be associated with regulation of index protein expression in Ghrelin-CaM-MLCK signaling pathway.

Osthole inhibits histamine-dependent itch via modulating TRPV1 activity.

Osthole, an active coumarin isolated from Cnidium monnieri (L.) Cusson, has long been used in China as an antipruritic herbal medicine; however, the antipruitic mechanism of osthole is unknown. We studied the molecular mechanism of osthole in histamine-dependent itch by behavioral test, Ca(2+) imaging, and electrophysiological experiments. First, osthole clearly remitted the scratching behaviors of mice induced with histamine, HTMT, and VUF8430. Second, in cultured dorsal root ganglion (DRG) neurons, osthole showed a dose-dependent inhibitory effect to histamine. On the same neurons, osthole also decreased the response to capsaicin and histamine. In further tests, the capsaicin-induced inward currents were inhibited by osthole. These results revealed that osthole inhibited histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how osthole exerts anti-pruritus effects and suggests that osthole may be a useful treatment medicine for histamine-dependent itch.

Neovibsanin B inhibits human malignant brain tumor cell line proliferation and induces apoptosis.

The present study was designed to examine the effect of neovibsanin B on glioma cell viability, apoptosis and on the survival time in mice bearing tumor xenografts. The results demonstrated that neovibsanin B significantly reduced the cell viability of GL261-NS and GL261-AC cells in a dose-dependent manner. However the inhibition of proliferation was more significant in GL261-NS cells. The IC50 value of neovibsanin B against GL261-NS and GL261-AC cells is 5 and 25 nM, respectively. The inhibitory effect of neovibsanin B on cell growth was more effective than that of vincristine (VCR) (P < 0.05). We also observed a significant decrease in sphere-forming ability of GL261-NS cells on treatment with neovibsanin B. The number of colonies formed by GL261-NS cells on treatment with neovibsanin B, VCR and DMSO were 3.34 ± 1.02, 12.53 ± 3.46 and 61.34 ± 9.89% respectively after 7 days. The flow cytometry revealed a marked increase in apoptotic cell death of GL261-NS cells on treatment with neovibsanin B. The western blots showed a significant decrease in the level of activated caspase-3 on treatment with neovibsanin B after 24 h. In addition, neovibsanin B increased the median survival time of glioma-bearing mice (P < 0.05). Therefore, neovibsanin B effectively inhibits glioma cell viability by inducing apoptosis, and can be a potent therapeutic agent for the treatment of malignant glioma.

[Clinical effects of the circumcision stapler, foreskin cerclage, and traditional circumcision: A comparative study].

OBJECTIVE: To compare the clinical effects of the circumcision stapler, circumcision cerclage, and traditional circumcision in the treatment of phimosis and redundant prepuce. METHODS: Using the circumcision stapler (group A), foreskin cerclage (group B), and traditional circumcision (group C), we treated 276 patients with phimosis or redundant prepuce. We made comparisons among the three groups in the operation time, intraoperative blood loss, intraoperative and 24-hour postoperative pain scores, and incidence of postoperative complications. Results: The operation time, intraoperative blood loss, and intraoperative pain score were (6.52 ± 2.45) min, (1.93 ± 0.82) ml, and 1.37 ± 0.68 in group A and (7.24 ± 1.86) min, (1.51 ± 0.72) ml, and 1.20 ± 0.79 in group B, all significantly lower than (28. 36 ± 4.22) min, (9.52 ± 3.29) ml, and 3.06 ± 0.75 in group C (P <0.05). The 24-hour postoperative pain score was remarkably higher in group B than in A and C (3. 18 ± 0. 82 vs 1. 85 ± 0. 63 and 1. 82 ± 0. 75, P <0. 05). The incidence rate of postoperative complications was markedly lower in group A than in B (5. 43% vs 14. 13%, P < 0.05), but with no significant differences between either A and C or B and C (P >0.05). CONCLUSION: The circumcision stapler, with its advantages of simple operation, minimal invasiveness, fewer complications, and better cosmetic result, deserves a wider clinical application.

Daucosterol protects neurons against oxygen-glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway.

We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3ß(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.

Daucosterol promotes the proliferation of neural stem cells.

Neural stem cells (NSCs) are self-regenerating cells, but their regenerative capacity is limited. The present study was conducted to investigate the effect of daucosterol (a sterolin) on the promotion of NSC proliferation and determine the corresponding molecular mechanism. Results of cell counting kit-8 (CCK-8) assay showed that daucosterol significantly increased the quantity of viable cells and the effectiveness of daucosterol was similar to that of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Flow cytometry detection of CFSE-labeled (CFSE, carboxyfluorescein diacetate succinimidyl ester) NSCs showed that Div Index (or the average number of cell divisions) and % Divided (or the percentage of cells that divided at least once) of the cells were increased, indicating that daucosterol increased the percentage of NSCs re-entering the cell cycle. mRNA microarray analysis showed that 333 genes that are mostly involved in the mitotic cell cycle were up-regulated. By contrast, 627 genes that are mostly involved in differentiation were down-regulated. In particular, insulin-like growth factor I (IGF1) was considered as an important regulatory gene that functionally promoted NSC proliferation, and the increased expression of IGF1 protein was validated by ELISA. In addition, the phosphorylation of AKT was increased, indicating that the proliferation-enhancing activity of daucosterol may be involved in IGF1-AKT pathway. Our study provided information about daucosterol as an efficient and inexpensive growth factor alternative that could be used in clinical medicine and research applications.

Pinching spine: A potential treatment for depression.

OBJECTIVE: To investigate whether pinching spine (PS, i.e. , a traditional Chinese manipulative therapy) is beneficial to ameliorating the depressive state (including behavioral deficit, retardative weight gain and decreased sucrose consumption) in a rat model of depression induced by chronic unpredictable stress (CUS) and to explore the candidate mechanism of action. METHODS: PS was performed on rats' spine once daily for 1 week after exposure to CUS. The open-field test, body weight measuring, and sucrose intake test were applied on different dates: before stress (d0), at the end of stress (d21) and after PS treatment (d28), respectively. Then the rats' hippocampuses were performed genome-wide microarray analysis, and the expression levels of several genes were evaluated by real-time polymerase chain reaction (PCR). RESULTS: Exposure to CUS resulted in decreases of behavioral activity and sucrose consumption, which were reversed significantly after PS treatment. The expression of several genes relevant to energy metabolism, anti-oxidation, and olfactory receptor, etc., were down-regulated, while the expression of those relevant to hemostasis, immunity-inflammation, and restriction of activities and ingestion, etc., were up-regulated in hippocampuses of rats exposed to CUS. PS treatment significantly inverted these changes. Furthermore, increase or decrease in gene expression evaluated by realtime PCR was concordant with up-regulated or down-regulated expression evaluated by microarray analysis. CONCLUSION: PS showed a potential antidepressant-like effect, of which the action mechanism might be due to gene expression regulation in hippocampus.

Microarray Analysis of mRNA and MicroRNA Expression Profile Reveals the Role of ß -Sitosterol-D-glucoside in the Proliferation of Neural Stem Cell.

Neural stem cells (NSCs) are self-regenerating cells, but their regenerative capacity is limited. The present study was conducted to investigate the effect of ß -sitosterol-D-glucoside (BSSG) on the proliferation of hippocampal NSCs and to determine the corresponding molecular mechanism. Results of CCK-8 assay showed that BSSG significantly increased NSC proliferation and the effectiveness of BSSG was similar to that of basic fibroblast growth factor and epidermal growth factor. mRNA expression profiling showed that 960 genes were differentially expressed after NSCs were treated with BSSG. Among the 960 genes, IGF1 is considered as a key regulatory gene that functionally promotes NSC proliferation. MicroRNA (miRNA) expression profiling indicated that 30 and 84 miRNAs were upregulated and downregulated, respectively. miRNA-mRNA relevance analysis revealed that numerous mRNAs including IGF1 mRNA were negatively regulated by miRNAs with decreased expression, thereby increasing the corresponding mRNA expression. The increased expression of IGF1 protein was validated by ELISA. Picropodophyllin (PPP, an inhibitor of IGF-1R) inhibition test confirmed that the proliferation-enhancing effect depended on IGF1. This study provided information about BSSG as an efficient and inexpensive growth factor alternative, of which the effect is closely involved in IGF1.