TFR1-Mediated Iron Metabolism Orchestrates Tumor Ferroptosis and Immunity in Non-Small Cell Lung Cancer.

This study aimed to investigate the underlying molecular mechanisms of transferrin receptor (TFR1) in non-small cell lung cancer (NSCLC). Histological analysis was performed using hematoxylin-eosin (HE) staining. The number of CD8+ T cell were determined by flow cytometry and immunofluorescence assays. mRNA levels were analyzed by qRT-PCR. Protein expression was detected by western blot. Ferroptosis was detected by using propidium iodide (PI) staining. Xenograft experiment was applied for determining tumor growth. The results showed that interferon (IFN)-γ plus iron dextran (FeDx) induced iron overload and the ferroptosis of NSCLC cells. Moreover, IFN-γ-mediated upregulation of TFR1 promoted ferritinophagy and tumor cell ferroptosis via blocking via blocking ferritin heavy chain 1 (FTH1)/ ferritin light chain (FTL) signaling. However, TFR1 knockout suppressed the ferroptosis of tumor cells. Furthermore, FeDx-mediated iron overload promoted the sensitivity of anti-programmed death ligand 1 (PD-L1) therapies. Clinically, TFR1 was downregulated in NSCLC patients. Low levels of TFR1 predicted decreased CD8+ T cells. Taken together, IFN-γ combined with iron metabolism therapies may provide a novel alternative for NSCLC.

TGF-ß1 Inhibits Osteoclast Differentiation and Abnormal Angiogenesis in Intervertebral Disc Degeneration: Evidence from RNA Sequencing and Animal Studies.

OBJECTIVE: Mechanisms involved in developing intervertebral disc degeneration (IDD) are poorly understood, thus making developing effective therapies difficult. This study aimed to suggest a possible molecular mechanism, based on transcriptome sequencing-identified transforming growth factor (TGF-ß), underlying the effects on bone homeostasis in IDD. METHODS: A mouse model for IDD was established. Transcriptome sequencing of nucleus pulposus tissue from mice (n = 3) identified differentially expressed mRNAs and key genes impacting bone homeostasis. A protein-protein interaction network pinpointed core genes. GO and KEGG analysis revealed gene functions. Expression levels of TGF-ß1, tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were measured. Micro-CT evaluated vertebral structures and vascular imaging. Western Blot measured expression levels of Vegf, Opn, MMP3, and MMP13. Safranin O-Fast Green and TRAP staining were performed on intervertebral discs and endplates. RESULTS: Transcriptomic analysis found 1790 differentially expressed mRNAs in IDD mice. Twenty-eight genes related to bone homeostasis in IDD were identified. TGF-ß1 was confirmed as the core gene. GO and KEGG showed TGF-ß1 regulates osteoclast markers like CTSK and TRAP through pathways including NF-κB and MAPK. Experimental validation revealed lower TGF-ß1 expression in IDD mice than controls, and increased TRAP and CTSK expression. Micro-CT showed decreased bone mass and intervertebral disc space in IDD mice. Vascular imaging showed increased vascular volume in IDD cartilaginous endplates. Western blot displayed increased VEGF and OPN levels, but decreased MMP3 and MMP13 in IDD mice. Safranin O-fast green staining revealed severe IDD degeneration. However, TGF-ß1 injection improved bone parameters in IDD mice. In vitro experiments confirmed TGF-ß1 inhibits bone marrow macrophages differentiation into osteoclasts. CONCLUSION: From our data, we conclude that TGF-ß1 repressed osteoclast differentiation and aberrant bone-associated angiogenesis in cartilage endplates (EPs) to alleviate IDD, which may be instrumental for the therapeutic targeting of IDD.

Targeting TRIM9 by miR-218-5p Restricts Cell Proliferation and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer.

OBJECTIVE: Tripartite motif-containing protein 9 (TRIM9) has been studied in several human tumors. MicroRNA-218-5p (miR-218-5p) was predicted to target TRIM9. We aimed to investigate the roles of miR-218-5p/TRIM9 axis in non-small cell lung cancer (NSCLC). METHODS: TRIM9 and miR-218-5p expression levels in NSCLC tissues and cell lines (95D and H1299) were determined by reverse transcription quantitative PCR. UALCAN and Kaplan-Meier (KM) plotter were employed to analyze the expression level of TRIM9 in lung cancer. The interaction between TRIM9 and miR-218-5p was explored by luciferase reporter assay and Spearman correlation test. Immunohistochemistry assay was used to confirm the protein expression of TRIM9 in NSCLC tissues. Regulatory effects of TRIM9 or miR-218-5p on cell proliferation, migration and invasion, and epithelial-mesenchymal transition (EMT) process of NSCLC cells were assessed by CCK-8 assay, transwell assay and western blot analysis. RESULTS: MiR-218-5p was predicted to specifically target TRIM9 and confirmed to negatively regulate TRIM9 expression in NSCLC cells. Online bioinformatics analysis showed TRIM9 overexpression in lung cancer and predicted poor prognosis. The data from collected clinical specimens showed that miR-218-5p was downregulated, while TRIM9 was upregulated in NSCLC tissues, whose expression levels were negatively correlated. The in vitro experiments demonstrated that TRIM9 knockdown imitated the suppressive effects miR-218-5p overexpression on cell proliferation, migration, invasion and EMT process. In addition, overexpression of TRIM9 reversed the effects of miR-218-5p in NSCLC cells. CONCLUSIONS: Our results suggest that TRIM9 functions as an oncogene in NSCLC in vitro and is regulated by miR-218-5p.

Effect of Copper Addition on the Formability of 304L Austenitic Stainless Steel.

To improve the antibacterial properties of 304L austenitic stainless steel, copper is often added as an antibacterial agent, but the forming performance of the resulting material is poor, impacting its actual production and use. Therefore, this study investigated the influence of copper addition on the formability of 304L austenitic stainless steel with drawing, cupping and conical cup forming tests. Mechanical properties were determined with tensile and hardness tests. The microstructure and phase transformation were further characterized by metallographic microscopy, scanning electron microscopy and x-ray diffraction analysis. It was found that the addition of copper impaired the mechanical properties of 304L austenitic stainless steel, increased the stacking fault energy of the material and inhibited the occurrence of strain-induced martensite transformation, leading to a decrease in the formability of 304L austenitic stainless steel.

KMT5A Knockdown Suppresses Osteosarcoma Cell Proliferation and Metastasis Through Ꞵ-Catenin Signalling.

PURPOSE: Osteosarcoma (OS) is the most common malignant solid bone tumor in children and young adults. We aimed to investigate the effects and cellular mechanisms of KMT5A on OS cell activity. METHODS: The protein expression was evaluated in the clinical normal, adjacent and OS osteogenic tissues. Knockdown of KMT5A was achieved by KMT5A siRNAs in a human OS cell line, MG63, to detect cell proliferation and metastasis. RESULTS: KMT5A expression was upregulated in clinical OS tissues. Knockdown of KMT5A inhibited cell proliferation but enhanced cell death, with significantly reduced cyclinD1 and Bcl2 and increased cleaved-caspase9 levels. KMT5A knockdown also suppressed OS cell migration and invasion capacity and deceased MMP3 and vimentin expression. ß-catenin levels were upregulated in OS tissues and blocking KMT5A resulted in a significant decline in ß-catenin expression in the OS cells. Further administration of ß-catenin activator remarkably increased protein levels of KMT5A, cyclinD1, Bcl2, MMP3, and vimentin, which showed reversed effects of KMT5A knockdown on OS cell activity. CONCLUSION: KMT5A knockdown plays an inhibitory role in OS cell proliferation and metastasis through ß-catenin signalling, which provides basic evidence and suggests potential targets for OS therapeutic research.

SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/ß-catenin pathway and ameliorates disc degeneration.

This study aimed to determine the effects of SKI on interleukin (IL)-1ß-induced apoptosis of nucleus pulposus (NP) cells, intervertebral disc degeneration (IDD), and the Wnt signaling pathway. NP tissue specimens of different Pfirrmann grades (II-V) were collected from patients with different grades of IDD. Real-time polymerase chain reaction and western blotting were used to compare SKI mRNA and protein expression in NP tissues from patients. Using the IL-1ß-induced IDD model, NP cells were infected with lentivirus-coated si-SKI to downregulate the expression of SKI and treated with LiCl to evaluate the involvement of the Wnt/ß-catenin signaling pathway. Western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect NP cell apoptosis, extracellular matrix (ECM) metabolism, and related protein expression changes in the Wnt/ß-catenin signaling pathway. To investigate the role of SKI in vivo, a rat IDD model was established by needle puncture of the intervertebral disc. Rats were injected with lentivirus-coated si-SKI and evaluated by magnetic resonance imaging (MRI), and hematoxylin and eosin (HE) and safranin O staining. SKI expression positively correlated with the severity of human IDD. In the IL-1ß-induced NP cell degeneration model, SKI expression increased significantly and reached a peak at 24 h. SKI knockdown protected against IL-1ß-induced NP cell apoptosis and ECM degradation. LiCl treatment reversed the protective effects of si-SKI on NP cells. Furthermore, lentivirus-coated si-SKI injection partially reversed the NP tissue damage in the IDD model in vivo. SKI knockdown reduced NP cell apoptosis and ECM degradation by inhibiting the Wnt/ß-catenin signaling pathway, ultimately protecting against IDD. Therefore, SKI may be an effective target for IDD treatment.

New Hope for Intervertebral Disc Degeneration: Bone Marrow Mesenchymal Stem Cells and Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Transplantation.

Bone Marrow Mesenchymal Stem Cells (BMSCs), multidirectional cells with self-renewal capacity, can differentiate into many cell types and play essential roles in tissue healing and regenerative medicine. Cell experiments and in vivo research in animal models have shown that BMSCs can repair degenerative discs by promoting cell proliferation and expressing Extracellular Matrix (ECM) components, such as type II collagen and protein-polysaccharides. Delaying or reversing the Intervertebral Disc Degeneration (IDD) process at an etiological level may be an effective strategy. However, despite increasingly in-depth research, some deficiencies in cell transplantation timing and strategy remain, preventing the clinical application of cell transplantation. Exosomes exhibit the characteristics of the mother cells from which they are secreted and can inhibit Nucleus Pulposus Cell (NPC) apoptosis and delay IDD through intercellular communication. Furthermore, the use of exosomes effectively avoids problems associated with cell transplantation, such as immune rejection. This manuscript introduces almost all of the BMSCs and exosomes derived from BMSCs (BMSCs-Exos) described in the IDD literature. Many challenges regarding the use of cell transplantation and therapeutic exosome intervention for IDD remain to be overcome.

Curriculum content and approaches for integrating health education into physical education in college settings / 中国学校卫生

Abstract@#The integration of health education into physical education in colleges is an important carrier to achieve the goal of school health education, and an inevitable requirement for improving health literacy of college students. Exploration and construction of one curriculum content system integrating health knowledge and sports skills, mental health and sports spirit, basic theory of physiology, sports injury and disease prevention. The integration of health education into physical education includes curriculum and material design, classroom based teaching process, as well as teaching assessment inside and outside the classroom, developing a multi faceted, multi level and multi angle optimized implementation approach, aiming to explore the joint connection of health education and physical education, the implementation of Lide Shuren can better achieve the cultivation of students health awareness and healthy lifestyle, and lay a solid foundation for lifelong health.

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.

Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly induced by the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (ERS) pathway. This article mainly summarizes the factors that induce IDD and apoptosis, the relationship between the three apoptotic pathways and IDD, and potential therapeutic strategies. Preliminary animal and cell experiments show that targeting apoptotic pathway genes or drug inhibition can effectively inhibit IVD cell apoptosis and slow IDD progression. Targeted apoptotic pathway inhibition may be an effective strategy to alleviate IDD at the gene level. This manuscript provides new insights and ideas for IDD therapy.

Comparison between zero-profile and cage plate devices in the treatment of single-level cervical spondylopathy.

OBJECTIVE: To compare the new zero-profile (Zero-P) fusion cage with regular cage and plate (CP) in the treatment of anterior cervical single-level cervical degenerative diseases. METHODS: Patients operated from January 2013 to August 2018 were enrolled. They were divided into the Zero-P group (n = 74 cases) and CP groups (n = 116 cases). Follow-up assessment was at 1, 3, 12, and 24 months after surgery, including the incidence of dysphagia, visual analogue scale (VAS) score, Japanese orthopaedic association (JOA)score, C2-C7 Cobb angle, intervertebral disc height (IDH) and adjacent joint degeneration. RESULTS: The operation time and blood loss of patients in Zero-P group were less than those in the CP group, and there was no difference in hospitalization time. All 190 patients were followed up for 24 to 72 months, with an average of 35.29 months. In terms of clinical outcomes, vas and JOA scores of the two groups were significantly improved at one month and the last follow-up. The incidence of dysphagia in the Zero-P group was lower than that in the CP group. On radiological effects, Cobb angle and IDH showed significant correction in both groups, but the degeneration rate of adjacent joints in the Zero-P group was lower than the CP group. CONCLUSIONS: In ACDF, the clinical and radiological results of Zero-P and CP devices are satisfactory, but Zero-P cage may be superior in operation time, blood loss, the incidence of dysphagia and adjacent joint degeneration.

Exosomes in osteosarcoma research and preclinical practice.

Osteosarcoma (OS) is a rare soft-tissue malignant tumor with high lung metastasis and mortality rates. Preoperative chemotherapy, surgical resection of the lesion and postoperative chemotherapy are still the main treatments for osteosarcoma. The prognosis, however, is poor for patients with nonresectable, primary metastatic or relapsed disease. Recent studies have shown that targeted therapy for OS based on the characteristics of exosomes is very attractive. Exosomes are nanosized extracellular vesicles (EVs) that participate in cell-to-cell communication by transporting biologically active cargo molecules, causing changes in OS cell function and playing important roles in OS disease progression. With the characteristics of secretory cells, exosomes transport cargo (e.g., microRNAs) that can be used to detect the progress of a disease and can serve as markers and/or therapeutic targets for clinical diagnosis of OS. In this review, the roles of exosomes in OS pathogenesis, invasion, metastasis, drug resistance, diagnosis and treatment are summarized. In addition, this article elaborates a series of challenges to overcome before exosomes are applied in clinical practice and provides suggestions based on current evidence for the direction of future research.

Screening of osteoarthritis diagnostic markers based on immune-related genes and immune infiltration.

Osteoarthritis (OA) is a chronic degenerative disease of the bone and joints. Immune-related genes and immune cell infiltration are important in OA development. We analyzed immune-related genes and immune infiltrates to identify OA diagnostic markers. The datasets GSE51588, GSE55235, GSE55457, GSE82107, and GSE114007 were downloaded from the Gene Expression Omnibus database. First, R software was used to identify differentially expressed genes (DEGs) and differentially expressed immune-related genes (DEIRGs), and functional correlation analysis was conducted. Second, CIBERSORT was used to evaluate infiltration of immune cells in OA tissue. Finally, the least absolute shrinkage and selection operator logistic regression algorithm and support vector machine-recurrent feature elimination algorithm were used to screen and verify diagnostic markers of OA. A total of 711 DEGs and 270 DEIRGs were identified in this study. Functional enrichment analysis showed that the DEGs and DEIRGs are closely related to cellular calcium ion homeostasis, ion channel complexes, chemokine signaling pathways, and JAK-STAT signaling pathways. Differential analysis of immune cell infiltration showed that M1 macrophage infiltration was increased but that mast cell and neutrophil infiltration were decreased in OA samples. The machine learning algorithm cross-identified 15 biomarkers (BTC, PSMD8, TLR3, IL7, APOD, CIITA, IFIH1, CDC42, FGF9, TNFAIP3, CX3CR1, ERAP2, SEMA3D, MPO, and plasma cells). According to pass validation, all 15 biomarkers had high diagnostic efficacy (AUC > 0.7), and the diagnostic efficiency was higher when the 15 biomarkers were fitted into one variable (AUC = 0.758). We developed 15 biomarkers for OA diagnosis. The findings provide a new understanding of the molecular mechanism of OA from the perspective of immunology.

Alginic acid inhibits non-small cell lung cancer-induced angiogenesis via activating miR-506 expression.

Angiogenesis is a key event in non-small cell lung cancer progression. Alginic acid (AA), a kind of naturally occurring polyuronic acid, is generally enriched in edible brown algae. Recent studies have uncovered its anti-anaphylactic and anti-inflammatory properties. However, the effects of AA on human malignancies remain unknown. Herein, efficient inhibition of AA on NSCLC-induced angiogenesis was observed with tube formation and xenograft models. Subsequent results indicated that AA downregulated the expression of VEGF-A, a key angiogenesis-inducing cytokine. In addition, AA downregulated STAT3, a transcriptional inducer of VEGF-A and increased non-coding RNA miR-506 expression, respectively. Furthermore, miR-506 directly modulated STAT3 relying on base pairing the 3'-UTR in STAT3 mRNA. We also found that abrogation of miR-506 abolished the inhibitory effect of AA on VEGF-A expression and NSCLC-induced angiogenesis. Finally, xenografts experiments also showed that oral administration of AA could significantly attenuate NSCLC angiogenesis, indicated by decreased micro-vessel density (MVD) and the MVD marker CD31 expression in xenografts tissues. Correspondingly, AA treatment also downregulated VEGF-A, STAT3 and increased miR-506 expression in xenografts samples, respectively. Taken together, these results suggested that AA could suppress NSCLC-induced angiogenesis via miR-506/STAT3/VEGF-A axis. .

Sealing the Intramedullary Femoral Canal for Blood Loss in Total Knee Arthroplasty: A Meta-analysis of Randomized Controlled Trials.

Blood loss after total knee arthroplasty (TKA) is a potentially serious medical problem since it leads to anemia, increased need for transfusion, and prolonged hospitalization. Some studies have reported that sealing of the intramedullary femoral canal during TKA may decrease postoperative blood loss. The purpose of this study is to determine the effects of sealing of the intramedullary femoral canal during TKA on blood loss and transfusion rate. Electronic databases, PubMed, EMBASE, the Cochrane Library, Web of Science, and Chinese Biomedical Database, were systematically searched. Only randomized controlled trials (RCTs) that compared the sealing group with the control group during TKA were included up to March 2019. Two reviewers independently extracted data and assessed the quality of included studies. The statistical analysis was performed by using Review Manager 5.3 software. Cochrane Risk of Bias tool was used for quality assessment. Overall, eight RCTs involving 996 patients met our criteria and were analyzed. The results of meta-analysis showed that patients in the sealed group had less total blood loss, less total drain output and less hidden blood loss, less transfusion rates, a lower drop of hemoglobin level at day 1 postoperatively, and less hematoma than the control group. On the other hand, there were no significant differences in infection, deep vein thrombosis, and redness of incision between sealed and control group. Current meta-analysis found that sealing the femoral canal during TKA was an effective method for the control of blood loss.

Physical exercises and associated factors among college students during COVID-19 pandemic / 中国学校卫生

Objective@#To understand physical exercises and associated factors among college students COVID-19 pandemic, and to provide a reference for promoting physical exercise of college students at home.@*Methods@#A convenient questionnaire survey was used to investigate the physical exercise and associated factors of 1 132 college students in 6 colleges in Beijing.@*Results@#A total of 1 033(91.25%) college students participated in physical exercise; with an average of(3.33±1.99)times per week, the length of each exercise was (39.24±13.23)min, and the subjective sense of exercise intensity was(2.61±0.99). Differences in exercise frequency, duration and intensity differed significantly by gender(P<0.05). Differences in exercise frequency were significantly by grades and places of residence(P<0.05). The exercise items of college students differed by genders and places of residence were statistically significant(P<0.05). Students with different exercise motivations showed significant differences in exercise behaviors(P<0.05). Multivariate Logistic regression analysis showed that grade, lack of interest in exercise, limited venues, incomplete equipment, family sports atmosphere, and school requirements were associated with participation in physical exercise behavior at home(P<0.05).@*Conclusion@#The status of home physical exercise for college students needs to be improved. It is necessary to combine college students exercise motivation and characteristics of exercise items based on school physical education,and to establish a family-school-society network interactive platform to form an effective linkage mechanism to promote college students active participation in physical exercise at home.

A Data-Driven Volitional EMG Extraction Algorithm During Functional Electrical Stimulation With Time Variant Parameters.

OBJECTIVES: The goal of this study is to design a novel approach for extracting volitional electromyography (vEMG) contaminated by functional electrical stimulation (FES) with time variant amplitudes and frequencies. METHODS: A selective interpolation (SI) is adopted to eliminate the initial spike. Then the interpolated signal is decomposed into intrinsic mode functions by using complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN). Each IMF is window-filtered based on a logistic regression (LR) classifier to identify the IMFs contaminated by FES. Semi-simulated signals were generated using EMG and stimulation response and three metrics were adopted to validate the performance of the proposed algorithm, including the a) signal-to-noise ratio (SNR), b) normalized root mean squared error (NRMSE) and c) cross-correlation coefficient between the clean EMG and the extracted EMG. Real FES-contaminated EMG was collected from six able bodied volunteers and one stroke patient. The correlation coefficients between the extracted EMG and the wrist torque were analyzed. RESULTS: The simulation results showed a higher SNR (2.12 to -2.13dB), higher correlation (0.88± 0.08) and lower NRMSE (0.78 to 1.29) than those of the comb filter and EMD-Notch algorithm. The EMG-Torque correlation coefficients were 0.75± 0.07 for monopolar pulses and 0.77± 0.12 for bipolar pulses. For the stroke patient, the algorithm also successfully extracted underlying vEMG from time variant FES noises. CONCLUSIONS: All results showed that SICEEMDAN-LR is capable of extracting EMG during FES with time-variant parameters.

Subxiphoid vs transthoracic approach thoracoscopic surgery for spontaneous pneumothorax: a propensity score-matched analysis.

BACKGROUND: The transthoracic thoracoscopic surgery is currently accepted as a favorable technique for bullectomy for primary spontaneous pneumothorax. Recently, uniportal subxiphoid thoracoscopic surgery has been proposed as an alternative to conventional transthoracic thoracoscopic surgery. METHODS: From November 2014 and January 2016, 127 consecutive patients who met the inclusion criteria were enrolled in this study. Among these patients, 32 were treated using subxipoid approach, whereas 95 were treated using transthoracic approach. Propensity score case-matching was performed to adjust for patient backgrounds. RESULTS: The two groups of 32 pairs were well matched for baseline and surgical characteristics. Patients who underwent subxipoid approach had a longer operation time than transthoracic approach (p = 0.004). The subgroup analysis showed that the operation time for bilateral bullectomy was similar between the groups (p = 0.986). There were no differences between the groups with respect to the hospital stay after surgery, chest drain duration, the number of the staples used for the operation, and postoperative recurrence. However, the provoked arrhythmias events during surgery were significantly higher in the subxiphoid approach group (p = 0.011). CONCLUSIONS: Although transthoracic thoracoscopic surgery for spontaneous pneumothorax is well established, uniportal subxiphoid thoracoscopic surgery may be a potentially alternative way to management of patients with spontaneous pneumothorax in selected cases, especially for bilateral surgery, but causions should be taked.

miR-671-5p inhibits gastric cancer cell proliferation and promotes cell apoptosis by targeting URGCP.

Various studies have demonstrated that microRNA (miRNA) serves an important role in the development of gastric cancer. However, the expression level, clinical significance and the biological function of miRNA in gastric cancer remain largely unknown. The present study investigated the exact roles of miR-671-5p in gastric cancer, confirmed its target and explored its mechanism. Initially, the low expression levels of miR-671-5p in gastric cancer cells were confirmed by reverse transcription-quantitative polymerase chain reaction. TargetScan and MiRanda databases were utilized to forecast the target genes of miR-671-5p, and the prediction was verified by dual-luciferase reporter assay and western blot analysis. Cell Counting Kit-8 was used for cell proliferation detection. An annexin V-fluorescein isothiocyanate kit was used for cell apoptosis determination. Western blot analysis was adopted to measure the protein expression levels in different groups. The results of the present study revealed that there were lower expression levels of miR-671-5p in gastric cancer cells than in normal gastric cells. Upregulator of cell proliferation (URGCP) is a direct target of miR-671-5p and it may be negatively regulated by miR-671-5p. miR-671-5p mimics induced reduction of MKN28 cell proliferation. miR-671-5p mimics caused upregulation of MKN28 cell apoptosis. In addition, western blotting results indicated that the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein was significantly decreased in the miR-671-5p mimic group compared with the negative control group (P<0.01). These results suggested that miR-671-5p had a protective role in gastric cancer through inhibiting gastric cancer cell proliferation and promoting cell apoptosis by targeting URGCP. Therefore, miR-671-5p may be an effective therapeutic target for gastric cancer.

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-ß1 (TGF-ß1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-ß1 receptors, can regulate the activation of TGF-ß1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-ß1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis.