High mobility group AT-hook 2 promotes tumorigenicity of pancreatic cancer cells via upregulating ANLN.

HMGA2 is associated with the regulation of cellular biological processes in various human disorders and cancer progression, yet little is known about how HMGA2 controls tumorigenesis. This study uncovered the mechanism of HMGA2-mediated regulation of tumorigenicity in pancreatic cancer. We showed that HMGA2 was highly expressed in pancreatic cancer cells and correlated with poor prognosis. HMGA2 expression knockdown inhibited the tumorigenicity of pancreatic cancer cells. Conversely, overexpression of HMGA2 promoted tumorigenicity. Combination of ChIP-Seq, RNA-Seq and dual-luciferase reporter assays revealed HMGA2 could directly regulate ANLN expression. Furthermore, we found ANLN could mediate the HMGA2-induced effects on pancreatic cancer cells. The identification of the regulatory mechanism of HMGA2 and ANLN will provide insights into the progression for human pancreatic cancer.

α1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation.

Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by ß-adrenergic receptors (ß-ARs). However, α1-adrenergic receptors (α1-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α1-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α1-AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 µM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/- mice compared with wild-type mice. In conclusion, α1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

Is ERAS effective and safe in laparoscopic gastrectomy for gastric carcinoma? A meta-analysis.

BACKGROUND: It is still unclear whether enhanced recovery after surgery is effective and safe in laparoscopic gastrectomy for gastric carcinoma. METHODS: Cochrane library databases, Medline, Embase, and Pubmed were searched from January 1, 1986, to December 31, 2016. Randomized controlled trials (RCTs) comparing fast-track recovery with conventional recovery strategies in laparoscopic radical gastrectomy for gastric carcinoma were included. The main outcomes measured were postoperative hospital stay, time to first flatus, hospital charge, and overall complication rate. RESULTS: Six RCTs with 400 patients were included in this study. Fast-track surgery has shorter postoperative hospital stays (weighted mean difference (WMD) - 2.65; 95% CI, - 4.01 to - 1.29, z = 3.82, P < 0.01) and less hospitalization expenditure (WMD - 523.43; 95% CI, - 799.79 to - 247.06, z = 3.71, P < 0.01) than conventional recovery strategies. There was no significant difference with respect to duration to first flatus (WMD - 17.72; 95% CI, - 39.46-4.02, z = 1.60, P = 0.11) and complication rate (OR 1.57; 95% CI, 0.82-2.98, z = 1.37, P = 0.17). CONCLUSIONS: Enhanced recovery after surgery is effective and safe and is thus recommended in laparoscopic radical gastrectomy for gastric carcinoma.

[Current status of animal experiment report of acupuncture intervention in chronic fatigue syndrome based on ARRIVE guidelines and GSPC list].

OBJECTIVE: To analyze the current status of animal experiments of acupuncture in intervening chronic fatigue syndrome, so as to search formethods to improve the quality of animal experiment reports. METHODS: From the databases, such as CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, the literature of animal experiment on acupuncture treatment for chronic fatigue syndrome was searched from January 1st, 2011 to April 2nd, 2022. Data were extracted according to the animal research reporting in vivo experiment (ARRIVE) guidelines 2.0 and gold standard publication checklist (GSPC), and statistical analysis was performed using Excel 2019. RESULTS: A total of 16 studies were finally included. The satis-faction rate of essential items in the ARRIVE guidelines 2.0 is 41.76%，while the satisfaction rate of recommended items is only 27.73% and of the GSPC is 25.89%. Out of 16 studies, 13 of them explained the reasons for animal exclusion in the experiment, 8 provided specific randomized methods, 8 described detailed information on animal species, strains, and quantities, 3 basically indicated that they had passed ethical review, 7 explained the limitations of the research. All 16 studies reported the main findings and elucidated their potential clinical or scientific value. CONCLUSION: Current animal studies on acupuncture in intervening the chronic fatigue syndrome are of certain limitation. Descriptions of multiple items are incomplete or missing, which prevents rea-ders from assessing reliability and authenticity of the animal experiment. It is recommended that in future research, experimental design, execution and report should be carried out according to the report guidelines for animal experiment to improve research quality.

Mechanism of action of Daqinjiao decoction in treating cerebral small vessel disease explored using network pharmacology and molecular docking technology.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinically commonly-seen slow-progressing cerebral vascular disease. As a classic Chinese formula for the treatment of stroke, Daqinjiao Decoction (DQJD) is now used to treat CSVD with desirable effect. Since the mechanism of action is still unclear, this article will explore the therapeutic effect and mechanism of action of the formula using network pharmacology technology. METHODS: The major chemical components and potential target genes of DQJD were screened by bioinformatics. The key targets in CSVD were identified based on network modules. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Pharmacodynamics of the decoction was evaluated by establishing a rat model with bilateral common carotid artery occlusion in the brain. Molecular docking, Western blot analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to confirm the effectiveness of targets in related pathways. RESULTS: Network pharmacology showed that 16 targets and 30 pathways were involved in the DQJD-targeted pathway network. Results revealed that DQJD might play a role by targeting the key targets including Caspse3 and P53 and regulating the P53 signaling pathway. Cognitive function and neuronal cell changes of rats were evaluated using Morris water maze, open field test and HE staining. It was indicated that DQJD could keep the nerve cells intact and neatly arranged. The decoction could improve the memory and learning ability of rats compared with the model group. It decreased the protein and mRNA expression levels of Caspse3 and P53 significantly (p<0.01). CONCLUSION: The study shows that baicalein, quercetin and wogonin, the effective components of DQJD, may regulate multiple signaling pathways by targeting the targets like Caspse3 and P53 and treat CSVD by reducing the damage to brain nerve cells.

Minimally invasive surgery versus laparotomy of nonmetastatic pT4a colorectal cancer: a propensity score analysis.

AIM: The aim was to compare short-term and long-term oncological outcomes between minimally invasive surgery (MIS group) and laparotomy (lap group) in nonmetastatic pT4a colorectal cancer (CRC). MATERIALS AND METHODS: The study retrospectively analyzed the outcomes of 634 patients treated with radical operation from January 2015 to December 2021 for nonmetastatic pT4a CRC, with propensity score matching. RESULTS: The conversion rate from the MIS group to laparotomy is 3.5%. Intraoperative blood loss, time to first anal exhaust, defecation and drainage tube removal, and complication rate were significantly less in the MIS group. After 5 years, the outcomes of the MIS group were no inferior to laparotomy outcomes [overall survival (OS): 72.7 vs. 77.8%, P =0.285; disease-free survival (DFS): 72.2 vs. 75.0%, P =0.599]. And multivariate analysis showed that age greater than or equal to 60 years old, lymph node metastasis and the carcinoembryonic antigen levels were independent variables for OS, while lymph node metastasis and CA125 levels were independent variables for DFS. The results of the graph show the relationship between the sum of scores of sex, age, complications, BMI, carcinoembryonic antigen, age, CA125, tumor site, N stage and tumor length diameter and 1-year, 3-year, and 5-year mortality and DFS of patients. Among them, tumor length diameter and N stage are significantly correlated with long-term survival and disease-free of patients. CONCLUSION: MIS is safe and feasible for nonmetastatic pT4a CRC, with the added benefit of accelerated postoperative recovery. In oncology, MIS did not affect OS and DFS.

Meta-analysis of laparoscopic versus open colorectal surgery within fast-track perioperative care.

BACKGROUND: Both laparoscopic surgery and fast-track perioperative care have demonstrated advantages in patients undergoing elective colorectal resections. It is unclear whether there is an additive effect by combining these 2 procedures. OBJECTIVE: The study aimed to conduct a meta-analysis of the randomized evidence to compare laparoscopic with open colorectal surgery within fast-track perioperative care. DATA SOURCES: PubMed, MEDLINE, Embase, and the Cochrane library databases were electronically searched (January 1985 to August 2011). STUDY SELECTION: Randomized clinical trials compared laparoscopic with open colorectal resections within fast-track programs. INTERVENTION: Investigators independently reviewed articles, extracted data, and assessed study quality according to standardized criteria. MAIN OUTCOME MEASURES: The main outcomes measured were postoperative hospital stay, overall hospital stay, readmission rate, morbidity, and mortality. RESULTS: Three trials were considered suitable for meta-analysis. A total of 171 patients underwent laparoscopic surgery, and 142 had open surgery. Meta-analysis showed that laparoscopic colorectal surgery had shorter postoperative hospital stays (weighted mean difference -1.06; 95% CI, -2.06 to -0.06, z = 2.08, p = 0.04) and shorter overall hospital stays (weighted mean difference -2.04; 95% CI, -3.50 to -0.58, z = 2.74, p < 0.01). No significant differences were noted for readmission rate (OR 0.54; 95% CI, 0.26-1.12, z = 1.65, p = 0.10), morbidity (OR 0.68; 95% CI, 0.42-1.10, z =1.58, p = 0.11), and mortality (OR 0.33; 95% CI, 0.09-1.18, z =1.70, p = 0.09). No publication bias and no significant heterogeneity were noted. LIMITATIONS: This study was limited because of its small sample size. CONCLUSIONS: Laparoscopic colorectal surgery has shorter postoperative hospital stays and overall hospital stays than open surgery within fast-track perioperative care. There is no significant difference with respect to readmission rate, morbidity, and mortality. Because the number of patients included in the present trials was small, further studies should be undertaken to confirm these findings.

[Influence of clinical characteristics on health-related quality of life after mid-low rectal cancer surgery].

OBJECTIVE: The present study aims to investigate health-related quality of life (HRQOL) in disease-free survivors after radical surgery for mid-low rectal cancer. METHODS: A retrospective cross-sectional study was performed in patients with rectal cancer who underwent primary surgery between August 2002 and February 2011 by use of the European Organization for Research and Treatment of Cancer QLQ-C30 and CR-38 questionnaires (n = 330). The impact of clinical characteristics on HRQoL were assessed and compared by univariate and multivariate regression analyses. RESULTS: Two hundred and four effective responses were received. Patients with stoma were more impaired in HRQoL than those without stoma, especially in the field of social psychology, such as emotional function (M(50) = 91.67, U = 2668.5, P = 0.026), social function (M(50) = 83.33, U = 2095.5, P < 0.001), financial difficulties (M(50) = 0, U = 2240.5, P < 0.001) and body image (M(50) = 88.89, U = 2507.0, P = 0.013). Only in the constipation scale (M(50) = 14.29, U = 2376.0, P = 0.001), nonstoma patients had a better score. The analysis in different types of surgical procedure paralleled those of stoma. Patients with complication had a poorer function in some symptom scales such as dyspnoea (M(50) = 0, U = 1505.0, P < 0.001), gastro-intestinal symptom (M(50) = 6.67, U = 1766.0, P = 0.034) and financial difficulties (M(50) = 33.33, U = 1795.5, P = 0.044), and in some functioning scales such as emotional function (M(50) = 83.33, U = 1608.5, P = 0.009), cognitive function (M(50) = 66.67, U = 1612.5, P = 0.010) and body image (M(50) = 66.67, U = 1617.0, P = 0.012). In our study, HRQoL after rectal cancer surgery improved with time. Our multivariate analysis displayed that stoma and postoperative time were the most significant characteristics. Variables associated with worse financial status were less postoperative months, occurrence of complications and presence of stoma. CONCLUSIONS: Different scales of HRQoL in patients of China after curative surgery for mid-low rectal cancer are significantly influenced by different clinical characteristics.

[Construction and evaluation of a gradient stress model of PC12 cells induced by corticosterone].

Objective: A gradient stress model of PC12 cells induced by corticosterone was established to provide a basis for the evaluation and regulation of cell stress. Methods: The effect of corticosterone on cell viability was observed by measuring PC12 cell viability at different concentrations of corticosterone (0~1 000 µmol/L) after different intervention times (8~48 h) to screen the cell models for optimal intervention conditions. Key stress indicators (MDA, SOD, NADH, LDH) were measured spectrophotometrically and microscopically to evaluate the models. Results: When the concentration of corticosterone was below 200 µmol/L and the intervention time was 12 h, the cell viability was below half inactivation rate, which could reduce the confounding factors due to the decrease of cell viability in each group. Compared with the blank control group, corticosterone increased the levels of MDA, NADH and LDH,and decreased the levels of SOD in the model group in a concentration-dependent manner (P＜0.01), which was consistent with the construction of the gradient stress model. Conclusion: A gradient stress injury model of PC12 cells was successfully established, with intervention concentrations of 0 µmol/L, 25 µmol/L, 50 µmol/L, 100 µmol/L, 150 µmol/L and 200 µmol/L corticosterone at an intervention time of 12 h. The degree of stress injury of the cell model was increased gradually, which could be used as a basis and object for conducting cell stress injury assessment and regulation experiments.

Metal-Organic Framework Modified MoS2 Nanozyme for Synergetic Combating Drug-Resistant Bacterial Infections via Photothermal Effect and Photodynamic Modulated Peroxidase-Mimic Activity.

Bacterial infections have become major threats to public health all over the world. With the emergence of antibiotic resistance, it is urgent to develop novel antimicrobial materials to efficiently overcome drug resistance with high bactericidal activity. In this work, UiO-66-NH-CO-MoS2 nanocomposites (UNMS NCs) are constructed through the amidation reaction. The UNMS NCs are positively charged which is beneficial for capturing and restricting bacteria. Significantly, UNMS NCs possess a synergistic bactericidal efficiency based on near-infrared irradiation (808 nm) regulated combination of photothermal, photodynamic, and peroxidase-like enzymatic activities. Both the photodynamic property and nanozymatic activity of UNMS NCs can lead to the generation of reactive oxygen species. The UNMS NCs show high catalytic activity in a wide pH range and exhibit excellent antibacterial ability against ampicillin-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus with negligible cytotoxicity. Interestingly, due to the 808 nm irradiation-induced hyperthermia in the presence of UNMS NCs, the glutathione oxidation process can be accelerated, resulting in bacterial death more easily. Mice wound models are established to further manifest that UNMS NCs can promote wound healing with good biosafety in living systems.

The Impact of Quarantine on Pain Sensation among the General Population in China during the COVID-19 Pandemic.

During the pandemic era, quarantines might potentially have negative effects and disproportionately exacerbate health condition problems. We conducted this cross-sectional, national study to ascertain the prevalence of constant pain symptoms and how quarantines impacted the pain symptoms and identify the factors associated with constant pain to further guide reducing the prevalence of chronic pain for vulnerable people under the pandemic. The sociodemographic data, quarantine conditions, mental health situations and pain symptoms of the general population were collected. After adjusting for potential confounders, long-term quarantine (≥15 days) exposures were associated with an increased risk of constant pain complaints compared to those not under a quarantine (Odds Ratio (OR): 1.26; 95% Confidence Interval (CI): 1.03, 1.54; p = 0.026). Risk factors including unemployment (OR: 1.55), chronic disease history (OR: 2.38) and infection with COVID-19 (OR: 2.15), and any of mental health symptoms including depression, anxiety, insomnia and PTSD (OR: 5.44) were identified by a multivariable logistic regression. Additionally, mediation analysis revealed that the effects of the quarantine duration on pain symptoms were mediated by mental health symptoms (indirect effects: 0.075, p < 0.001). These results advocated that long-term quarantine measures were associated with an increased risk of experiencing pain, especially for vulnerable groups with COVID-19 infection and with mental health symptoms. The findings also suggest that reducing mental distress during the pandemic might contribute to reducing the burden of pain symptoms and prioritizing interventions for those experiencing a long-term quarantine.

Clinical features and risk factors for primary surgery in 205 patients with Crohn's disease: analysis of a South China cohort.

BACKGROUND: The frequency of Crohn's disease in China is increasing, but few reports are available on clinical features, phenotypes according to the Montreal classification, or risk factors for surgery in mainland China. OBJECTIVE: This study aimed to assess clinical presentation, phenotypes according to the Montreal classification, and potential risk factors for initial surgery in patients with Crohn's disease in southern China. DESIGN: This was an observational study designed as a retrospective analysis of a historical cohort. SETTINGS: The study was conducted at a tertiary referral hospital, Guangzhou, China. PATIENTS: Medical records of 212 consecutive patients with Crohn's disease were reviewed; data from 205 patients who met inclusion criteria were analyzed. MAIN OUTCOME MEASURES: The value of age, location, and behavior of disease according to the Montreal system, smoking behavior, and other clinical variables as potential risk factors in predicting the requirement for initial surgery was assessed by use of Cox regression analysis. RESULTS: A total of 205 patients were studied. Abdominal pain (181 patients, 88.3%) was the most common clinical presentation. At the time of diagnosis, age was between 17 and 40 years in 145 patients (70.7%). The Montreal classification of disease location was L3 (ileocolonic) in 114 patients (55.6%), disease behavior was classified as inflammatory in 133 patients (64.9%). During the course of their disease (median, 4 years; range, 1-21 years), 79 patients (38.5%) required bowel resection. Kaplan-Meier analysis showed that the overall cumulative rate of primary bowel surgery was 17.6% at 1 year after onset of symptoms, 20.3% at 2 years, 35.2% at 5 years, and 58.3% at 10 years. In our final Cox model, stricturing (HR, 3.67; 95% CI, 2.14-6.29; P < .001), penetrating behavior (HR, 4.60; 95% CI, 2.58-8.22; P < .001), and smoking habit (HR, 2.02; 95% CI, 1.15-3.53; P = .014) were significantly associated with an increased risk for bowel resection. LIMITATIONS: The study was limited by its retrospective nature. CONCLUSIONS: In Chinese patients with Crohn's disease, abdominal pain is the most common clinical presentation, and the most common phenotypes are age 17 to 40 years at diagnosis, ileocolonic disease location, and inflammatory disease behavior. More than one-third of patients require surgery at a median of 4 years after onset of symptoms. Stricturing, penetrating disease, and smoking are associated with an increased risk of requiring bowel resection.

Membrane nanotubes facilitate the propagation of inflammatory injury in the heart upon overactivation of the ß-adrenergic receptor.

Acute sympathetic stress quickly induces cardiac inflammation and injury, suggesting that pathogenic signals rapidly spread among cardiac cells and that cell-to-cell communication may play an important role in the subsequent cardiac injury. However, the underlying mechanism of this response is unknown. Our previous study demonstrated that acute ß-adrenergic receptor (ß-AR) signaling activates inflammasomes in the heart, which triggers the inflammatory cascade. In the present study, ß-AR overactivation induced inflammasome activation in both the cardiomyocytes and cardiac fibroblasts (CFs) of mice hearts following a subcutaneous injection of isoproterenol (ISO, 5 mg/kg body weight), a selective agonist of ß-AR. In isolated cardiac cells, ISO treatment only activated the inflammasomes in the cardiomyocytes but not the CFs. These results demonstrated that inflammasome activation was propagated from cardiomyocytes to CFs in the mice hearts. Further investigation revealed that the inflammasomes were activated in the cocultured CFs that connected with cardiomyocytes via membrane nanotubes (MNTs), a novel membrane structure that mediates distant intercellular connections and communication. Disruption of the MNTs with the microfilament polymerization inhibitor cytochalasin D (Cyto D) attenuated the inflammasome activation in the cocultured CFs. In addition, the MNT-mediated inflammasome activation in the CFs was blocked by deficiency of the inflammasome component NOD-like receptor protein 3 (NLRP3) in the cardiomyocytes, but not NLRP3 deficiency in the CFs. Moreover, ISO induced pyroptosis in the CFs cocultured with cardiomyocytes, and this process was inhibited by disruption of the MNTs with Cyto D or by the NLRP3 inhibitor MCC950 and the caspase-1 inhibitor Z-YVAD-FMK (FMK). Our study revealed that MNTs facilitate the rapid propagation of inflammasome activation among cardiac cells to promote pyroptosis in the early phase of ß-adrenergic insult. Therefore, preventing inflammasome transfer is a potential therapeutic strategy to alleviate acute ß-AR overactivation-induced cardiac injury.

Interference with the C-terminal structure of MARF1 causes defective oocyte meiotic division and female infertility in mice.

Meiosis-arrest female 1 (MARF1) is a recently identified key oogenic regulator essential for the maintenance of female fertility and genome integrity in mice. However, the detailed functions and the underlying mechanisms of MARF1 remain elusive. Here, in an attempt to create a mouse model expressing fluorescent protein-tagged MARF1 to facilitate further exploration of the roles of MARF1 in oocytes, we produced a Marf1-eGFP knockin (KI) mouse line in which the C-terminal structure and function of MARF1 were interfered by its fusing eGFP peptide. Using these Marf1-eGFP-KI mice, we revealed, unexpectedly, the functions of MARF1 in the control of oocyte meiotic division. We found that the Marf1-eGFP-KI females ovulated mature oocytes with severe meiotic and developmental defects, and thus were infertile. Moreover, meiotic reinitiation was delayed while meiotic completion was accelerated in the KI-oocytes, which was coincident with the increased incidence of oocyte aneuploidy. Therefore, MARF1 is indispensable for maintaining the fidelity of homolog segregation during oocyte maturation, and this function relies on its C-terminal domains.

Variation of plantaris muscle: a case report with clinical significance / Variación del músculo plantar: reporte de un caso con significado clínico

SUMMARY: The plantaris muscle is located between the soleus and gastrocnemius muscles, within the posterior calf group. Due to degeneration and its loss of plantar-flexion function, the muscle is vestigial in human beings, but it retains clinical significance. Few cases of variation in the plantaris muscle have been reported, and this, therefore, appears to be rare. Nonetheless, absence of this muscle was identified via the dissection of a left lower limb (male), which also indicated the absence of an attachment in the usual position. The present report, which addresses such variation, may provide both inspiration and reference points for the clinical treatment of so-called "tennis leg", and for the use of plantaris muscle for the purposes of clinical, autologous graft repair.

RESUMEN: El músculo plantar se ubica entre los músculos sóleo y gastrocnemio, dentro del grupo posterior de la pierna. Debido a la degeneración y la pérdida de la función de flexión plantar, el músculo es un vestigio en los seres humanos, pero conserva su importancia clínica. Se han informado pocos casos de variación en el músculo plantar y, por lo tanto, esto parece ser raro. No obstante, se observó la ausencia de este músculo durante la disección de un miembro inferior izquierdo (masculino). El presente informe, que aborda dicha variación, puede proporcionar puntos de referencia para el tratamiento clínico de la llamada "pierna de tenista" y para el uso del músculo plantar con fines de reparación clínica con injerto autólogo.

Effects of rhBMP-2 gene transfection to periodontal ligament cells on osteogenesis.

The present study aims to investigate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteogenesis of periodontal ligament (PDL) cells. The expression vector of rhBMP-2 (pcDNA3.1-rhBMP-2) was established. PDL cells were obtained through the enzymatic digestion and tissue explant methods and verified by immunohistochemistry. Cells were classified into experimental (cells transfected with pcDNA3.1/rhBMP-2-EGFP), blank (cells with no transfection) and control group (cells transfected with empty plasmid). rhBMP-2 expression was assessed via Western blotting analysis. The mineralization ability, alkaline phosphatase (ALP) activity and level of related osteogenic biomarkers were detected to evaluate the osteogenic characteristics of PDL cells. The rhBMP-2 expression vector (pcDNA3.1-rhBMP-2) was successfully established. Primary PDL cells displayed a star or long, spindle shape. The cultured cells were long, spindle-shaped, had a plump cell body and homogeneous cytoplasm and the ellipse nucleus contained two or three nucleoli. Cells displayed a radial, sheaf-like or eddy-like arrangement after adherence growth. Immunohistochemical staining confirmed that cells originated from mesenchymal opposed to epithelium. The experimental group exhibited an enhanced mineralization ability, higher ALP activity and increased expression of rhBMP-2 and osteogenic biomarkers (Runx2, collagen type I and osteocalcin) than the blank and control group. The present study demonstrated that rhBMP-2 transfection enhances the osteogenesis of PDL cells and provides a possibility for the application of rhBMP-2 expression products in dental disease treatment.

ZEB2 promotes tumor metastasis and correlates with poor prognosis of human colorectal cancer.

Colorectal cancer remains the most common cause of cancer-related deaths worldwide and it continues to lack an effective treatment. Here, we found that zinc finger E-box binding homeobox 2 (ZEB2) was overexpressed in several colorectal cancer cell lines and colorectal cancer specimens relative to adjacent non-cancerous tissues. Although ZEB2 has been reported to be associated with several tumors, its involvement in colorectal cancer progression remains unclear. In this study, we investigated the biological functions and molecular mechanisms of ZEB2 underlying colorectal carcinoma metastasis and angiogenesis. HCT116 colorectal cancer cells were treated with ZEB2 shRNA or recombinant ZEB2, and the expression of ZEB2 was assessed using reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting, respectively. Ectopic expression of ZEB2 induced proliferation and epithelial-mesenchymal transition (EMT), and increased the metastatic capacity of HCT116 cells in vitro and in vivo. Furthermore, endothelial cell tube formation and angiogenesis in chick embryo chorioallantoic membrane (CAM) were accelerated by conditioned medium from ZEB2-overexpressing HCT116 cells. Further, overexpression of ZEB2 accelerated tumor growth and angiogenesis in xenotransplantation models. However, silencing endogenous ZEB2 caused an opposite outcome. Our results provide new evidence that ZEB2 promotes the progression of colon cancer, and thereby might represent a novel therapeutic target for colorectal carcinoma.

Nanosize of zinc oxide and the effects on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets.

The aim of this study was to investigate the effect of dietary supplementation of nanosize zinc on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. Ninety-six LYD weanling piglets were assigned to control, zinc oxide (ZnO), organic-Zn (Zn-methionine) and nanosize ZnO (nano-Zn) groups with four replicates. The zinc was at the 120 mg/kg level in the treatment group's diet, while the control group's was 80 mg/kg Zn. The experiment results indicated that the nano-Zn and organic-Zn groups had significantly higher Zn digestibility compared to the ZnO and control groups. For the immune response traits, the IgG level and goat red blood cells (GRBC) antibody titer were nano-Zn and organic-Zn>ZnO>control; in the phytohemagglutinin (PHA) challenge test result, nano-Zn>organic-Zn>ZnO>control; in regard to the γ-globulin level, nano-Zn and organic-Zn>ZnO and control, with significant difference between groups. In the serum parameters aspect, serum Zn concentration in nano-Zn and organic-Zn groups were higher than in the ZnO and control groups, serum growth hormone concentration was increased in the nano-Zn group than in the other groups. In conclusion, nanosize zinc oxide for dietary supplementation can increase zinc digestibility, serum growth hormone levels and carbonic anhydrase activity and enhance the immune response of weanling piglets.

IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway.

Periodontal ligament stem cells (PDLSCs) are tissue-specific mesenchymal stem cells (MSCs), having an important role in regenerative therapy for teeth loss. Interleukin-7 (IL-7) is a key cytokine produced by stromal cells including MSCs, and exhibits specific roles for B and T cell development and osteoblasts differentiation of multiple myeloma. However, the effect of IL-7 on osteogenic differentiation of PDLSCs remains unclear. Therefore, in the present study we determined whether IL-7 affects the proliferation and osteogenic differentiation of PDLSCs in vitro and explored the associated signaling pathways for IL-7-mediated cell differentiation. The results demonstrated that the isolated human PDLSCs possessed MSCs features, highly expressing CD90, CD44, CD105, CD29 and CD73, and almost did not expressed CD34, CD45, CD11b, CD14 and CD117. IL-7 could not significantly affect the proliferation of PDLSCs, but it decreased their osteogenic differentiation and inhibited alkaline phosphatase (ALP) activity. The results of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting exhibited that the expression levels of Runx-2, SP7 and osteocalcin (OCN) were significantly reduced by IL-7. Further studies indicated that IL-7 did not significantly change JNK, ERK1/2 and p38 protein production, but markedly suppressed their phosphorylation levels. These data suggest that IL-7 inhibits the osteogenic differentiation of PDLSCs probably via inactivation of mitogen-activated protein kinase (MAPK) signaling pathway.

Tormentic acid inhibits LPS-induced inflammatory response in human gingival fibroblasts via inhibition of TLR4-mediated NF-κB and MAPK signalling pathway.

OBJECTIVE: Periodontal disease is one of the most prevalent oral diseases, which is associated with inflammation of the tooth-supporting tissues. Tormentic acid (TA), a triterpene isolated from Rosa rugosa, has been reported to exert anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of TA on lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs). METHODS: The levels of inflammatory cytokines such as interleukin (IL)-6 and chemokines such as IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), IκBα, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) was determined by Western blotting. RESULTS: The results showed that Porphyromonas gingivalis LPS significantly upregulated the expression of IL-6 and IL-8. TA inhibited the LPS-induced production of IL-6 and IL-8 in a dose-dependent manner. Furthermore, TA inhibited LPS-induced TLR4 expression; NF-κB activation; IκBα degradation; and phosphorylation of ERK, JNK, and P38. CONCLUSION: TA inhibits the LPS-induced inflammatory response in HGFs by suppressing the TLR4-mediated NF-κB and mitogen-activated protein kinase (MAPK) signalling pathway.