Comparison of surgical and endovascular left subclavian artery revascularization during thoracic aortic endovascular repair: a systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to incorporate data from the latest clinical studies and compare the safety and efficacy of surgical left subclavian artery (LSA) revascularization and endovascular LSA revascularization during thoracic endovascular aortic repair (TEVAR). Methods: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the PROSPERO database on 16 April 2023 (CRD42023414579). The Embase, MEDLINE (PubMed), and the Cochrane Library databases were searched from January 2000 to May 2023. Results: A total of 14 retrospective cohort studies with a total of 1,695 patients, were included for review. The peri-operative stroke rates of the surgical and endovascular LSA revascularization groups were 3.8% and 2.6%, respectively (P = 0.97). The peri-operative technical success rates for the surgical and endovascular LSA revascularization groups were 95.6% and 93.0%, respectively (P = 0.24). The peri-operative spinal cord ischemia rates were 1.6% (n = 18) and 1.9% (n = 7) in the surgical and endovascular LSA revascularization groups, respectively (P = 0.90). The peri-operative type Ⅰ endoleak rates for the surgical and endovascular LSA revascularization groups were 6.6% and 23.2%, respectively (P = 0.25). The subgroup analysis showed that the incidence of peri-operative type I endoleak in the parallel stent group was significantly higher than that in the surgical LSA revascularization group (P < 0.0001). The peri-operative left upper limb ischemia rates for the surgical and endovascular LSA revascularization groups were 1.2% and 0.6%, respectively (P = 0.96). The peri-operative mortality rates of the surgical and endovascular LSA revascularization groups were 2.0% and 2.0%, respectively (P = 0.88). Conclusion: There was no significant difference in the terms of short-term outcomes when comparing the two revascularization techniques. The quality of evidence assessed by GRADE scale was low to very-low. Surgical and endovascular LSA revascularization during TEVAR were both safe and effective. Compared with surgical LSA revascularization techniques, parallel stent revascularization of LSA significantly increased the rate of type I endoleak.

Diagnostic accuracy of sonication fluid cultures from prosthetic components in periprosthetic joint infection: an updated diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is the most serious complication following total joint arthroplasty (TJA) and has a significant impact on patients and the national healthcare system. To date, the diagnosis of PJI is still confronted with dilemmas. The present study investigated the validity of sonication fluid culture (SFC) for removing implants in the diagnosis of PJI after joint replacement. METHODS: From database establishment to December 2020, relevant literature was retrieved from the PubMed, Web of Science, Embase and Cochrane Library databases. Two reviewers independently performed quality assessment and data extraction to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under the curve (AUC) and diagnostic odds ratio (DOR) to evaluate the diagnostic value of overall SFC for PJI. RESULTS: A total of 38 eligible studies including 6302 patients were selected in this study. The pooled sensitivity, specificity, PLR, NLR, and DOR of SFC for PJI diagnosis were 0.77 (95% confidence interval [CI], 0.76-0.79), 0.96 (95% CI, 0.95-0.96), 18.68 (95% CI, 11.92-29.28), 0.24 (95% CI, 0.21-0.29), and 85.65 (95% CI, 56.46-129.94), respectively, while the AUC was 0.92. CONCLUSION: This meta-analysis showed that SFC was of great value in PJI diagnosis, and the evidence of SFC on PJI was more favorable but not yet strong. Therefore, improvement of the diagnostic accuracy of SFC is still necessary, and the diagnosis of PJI continues to warrant a multiplex approach before and during a revision procedure.

Circ_0027089 regulates NACC1 by targeting miR-136-5p to aggravate the development of hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is the main trigger of hepatocellular carcinoma (HCC). Circular RNA plays an indispensable role in cancer development, and this study aimed to disclose the function and mechanism of circ_0027089 in HBV-related HCC. The expression levels of circ_0027089, miR-136-5p and nucleus accumbens associated protein 1 (NACC1) mRNA were measured by quantitative real-time PCR, and the protein level of NACC1 was detected by western blot. For functional analyses, cell proliferation was assessed by cell counting kit-8 assay and colony formation assay. Cell apoptosis and cell cycle were detected by flow cytometry assay, and cell apoptosis was also assessed by caspase 3/7 activity. The capacities of migration and invasion were evaluated by wound healing assay and transwell assay, respectively. The predicted relationship between miR-136-5p and circ_0027089 or NACC1 was validated by dual-luciferase reporter assay and RNA binding protein immunoprecipitation assay. Animal experiments were performed in nude mice to explore the role of circ_0027089 in vivo. Circ_0027089 expression and NACC1 expression were elevated, while miR-136-5p expression was decreased in HBV-related HCC tissues and cells. In function, circ_0027089 knockdown inhibited HepG2.2.15 and HepAD38 (tet-off) cell proliferation, migration and invasion but induced cell cycle arrest and apoptosis, while circ_0027089 overexpression played the reversed effects. For mechanism exploration, miR-136-5p was a target of circ_0027089, and miR-136-5p deficiency could reverse the role of circ_0027089 knockdown. Circ_0027089 functioned as an oncogene to promote the development of HBV-related HCC by regulating NACC1 via competitively targeting miR-136-5p.

Clinical characteristics and outcomes of Stanford type B aortic intramural hematoma: A single centre experience.

Objective: To compare the clinical characteristics of Stanford type B aortic intramural hematoma (IMH) and Stanford type B aortic dissection (AD), and to identify the differences between thoracic endovascular aortic repair (TEVAR) and medical management (MM) in the Stanford type B IMH patients. Methods: A retrospective observational study was conducted in patients treated between January 2015 and December 2016. The clinical characteristics and CT images of patients with type B IMH and type B AD were compared, and the clinical characteristics and CT images of patients in the type B IMH group who were treated with TEVAR and MM were compared. Results: A total of 176 patients were included in this study, including 62 patients of type B IMH and 114 patients of type B AD. Five patients died in the IMH group and three in the AD group. The proximal hematoma or entry tear in both groups was mainly located in the descending aorta, and the proportion of the iliac artery involved in the AD group was significantly higher than that in the IMH group (31.6% vs. 8.1% P < 0.05). There were 50 MM patients and 12 TEVAR patients in the IMH group. No death occurred in the TEVAR group, while five patients in the MM group died. Seven patients in the MM group had disease progression vs. 12 in the TEVAR group (P < 0.05). The patients in the TEVAR group had more intima lesions than those in the MM group (83.3% vs. 30.0%, P < 0.05). TEVAR group involved more iliac artery hematoma than MM group (33.3% vs. 2.0%, P < 0.05). The maximum thickness of hematoma in TEVAR group was 14.9 ± 3.4 mm, which was significantly larger than that of MM group (10.2 ± 2.8 mm) (P < 0.05). Conclusion: In the diagnosis of IMH, patients' symptoms and high-risk signs of CTA should be paid attention to. TEVAR therapy should be actively considered on the basis of effective medical management when there are intima lesions (ULP/PAU), increased aortic diameter and hematoma thickness, extensive hematoma involvement, and pleural effusion.

Patellofemoral arthroplasty versus total knee arthroplasty for isolated patellofemoral osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Isolated patellofemoral osteoarthritis (PF-OA) is a common subtype of knee osteoarthritis, leading to a huge economic burden on health care systems. Although previous studies have shown that patellofemoral arthroplasty (PFA) and total knee arthroplasty (TKA) have good clinical effects, it remains largely unclear which treatment is more effective for patients with isolated PF-OA. We aimed to compare postoperative function, complications, revision rates, level of physical activity, and satisfaction rate between the two surgical techniques. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Search of literature was conducted in MEDLINE, EMBASE, Cochrane Library, and Web of Science until November 2020. The included studies were those that provided direct comparison of postoperative outcomes between PFA and TKA. Data were extracted from eligible studies and combined to calculate the pooled odds ratio (OR) and 95% confidence interval (CI). Sensitivity analysis and subgroup analysis were conducted to evaluate heterogeneity between the two groups. RESULTS: A total of 7 eligible studies (3 recent randomized controlled trials and 4 nonrandomized controlled trials) were included in this meta-analysis. The pooled results showed that both the PFA group and the TKA group had improved postoperative indicators, suggesting that the two operation modes could improve the knee function and quality of life of patients. Throughout the first 2 years postoperatively, higher activity level, and better functional recovery were observed for PFA compared with TKA in this study; moreover, the differences between the two operation modes were statistically significant (p < 0.05). We found no significant difference in complications, revision rates, and satisfaction rate between the two procedures. CONCLUSION: Although there was no observed difference in the complications, revision rates, and satisfaction rate between PFA and TKA, PFA was superior to TKA in terms of knee function and physical activity in the first 2 years postoperatively. Therefore, PFA is a safe, effective, and less invasive treatment for patients with isolated PF-OA. Our findings are consistent with the systematic review of current evidence that PFA may be more suitable for younger patients with high activity needs. Patient selection is, therefore, thought to be of paramount importance. Individualized surgical plan should be designed according to the patient's age, BMI, KOA site, and activity level and combined with the doctor's personal experience.

Efficacy and safety of abdominal acupuncture for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a disease based on degenerative pathological changes. Most commonly seen in the elderly and is one of Kenn's leading causes, its symptoms include swollen knees, pain in walking up and downstairs. If left untreated, it can lead to joint deformity and disability. Many clinical studies have reported that abdominal acupuncture has a good effect on KOA treatment, but there is no relevant systematic review. So the purpose of this study is to evaluate the effectiveness and safety of abdominal acupuncture in treating KOA. METHODS: The following 8 electronic databases will be searched, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Web of Science, Chinese Scientific Journal Database (VIP), Wanfang Database, and Chinese Biomedical Literatures Database (CBM) from their inception to November 1, 2020 without any restrictions. Researchers retrieve the literature and extracted the data, evaluation of research methods, quality of literature. The outcomes will include a Visual Analogue Scale. The Western Ontario and McMaster Universities Osteoarthritis Index, total effective rate, incidence of any adverse events. We use the Cochrane Risk of a bias assessment tool to evaluate methodological qualities. Data synthesis will be completed by RevMan 5.3.0. RESULTS: We will show the results of this study in a peer-reviewed journal. CONCLUSIONS: This meta-analysis will provide reliable evidence for abdominal acupuncture treatment of KOA. INPLASY REGISTRATION NUMBER: INPLASY2020110020.

Diagnostic Accuracy of the Synovial Fluid α-Defensin Lateral Flow Test in Periprosthetic Joint Infection: A Meta-analysis.

OBJECTIVES: There is a controversy on the diagnostic reliability and accuracy of synovial fluid α-defensin in periprosthetic joint infection (PJI). We performed this meta-analysis to evaluate the diagnostic accuracy of the α-defensin lateral flow test in PJI. METHODS: PubMed, Embase, and the Cochrane library were systematically searched, and articles (up to January 2020) on the diagnosis of hip and knee PJIs using the α-defensin Synovasure lateral flow test were included. The diagnostic accuracy of the α-defensin lateral flow test in PJI was evaluated using meta-analysis. The pooled sensitivity, specificity, accuracy, positive and negative likelihood ratio, diagnostic odds ratio, and post-test probabilities were calculated. RESULTS: Seventeen studies including 1443 cases were included. Meta-analysis showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and a diagnostic odds ratio was 0.83 (95% CI 0.77, 0.88), 0.95 (95% CI 0.93, 0.97), 16.86 (95% CI 11.67, 24.37), 0.17 (95% CI 0.13, 0.24) and 85.30 (95% CI 47.76, 152.35), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.97 (95% CI 0.95, 0.98). Subgroup analysis also confirmed the high efficiency of α-defensin Synovasure lateral flow test in diagnosing PJIs, irrespective of ethnicity. Fagan's nomogram analysis there was a high positive post-test probability of 94% and a low negative post-test probability of 15%. CONCLUSIONS: We indicated that the α-defensin lateral flow test had a high accuracy for diagnosing PJI. Large-scale studies are needed to validate its significance in PJI diagnosis.

Reliability of circulating fibrinogen in the diagnosis of prosthesis-related infections: a systematic review and meta-analysis.

BACKGROUND: Fibrinogen (FIB) has recently been used as a biomarker to diagnose periprosthetic joint infection (PJI), but its reliability is still questionable. The aim of this study was to investigate the accuracy of FIB in the diagnosis of PJI after joint replacement. METHODS: We searched for literatures published in PubMed, EMBASE, and the Cochrane Library from the time of database inception to September 2020 and screened the studies according to the inclusion criteria. Then, we calculated the diagnostic parameters of FIB, including the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under the curve (AUC), and diagnostic odds ratio (DOR). In addition, we implemented subgroup analyses to identify the sources of heterogeneity. RESULTS: Seven studies including 1341 patients were selected in our meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of FIB for PJI diagnosis were 0.78 (95% confidence interval [CI], 0.73-0.82), 0.83 (95% CI, 0.81-0.86), 4.60 (95% CI, 3.30-6.42), 0.24 (95% CI, 0.18-0.34), and 20.13 (95% CI, 14.80-27.36), respectively, while the AUC was 0.896. CONCLUSION: The present study indicated that FIB was a reliable detection method and might be introduced into the diagnostic criteria for PJI. However, more robust studies are still needed to confirm the current findings, because most of the included studies were retrospective and had small sample sizes.

Diagnostic accuracy of D-dimer in periprosthetic joint infection: a diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most devastating complications after total joint replacement (TJA). Up to now, the diagnosis of PJI is still in a dilemma. As a novel biomarker, whether D-dimer is valuable in the diagnosis of PJI remains controversial. This meta-analysis attempts to determine the diagnostic accuracy of D-dimer in PJI. METHODS: Relevant literature was retrieved from PubMed, Embase, Web of Science, and Cochrane Library (from database establishment to April 2020). Literature quality was evaluated using Revman (version 5.3). The random effect model was used in the Stata version 14.0 software to combine sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve, and area under SROC (AUC) to evaluate the diagnostic value of overall D-dimer for PJI. Meta regression and subgroup analysis were performed according to the threshold, the study design, the sample size, the diagnostic gold standard, the country of study, and the type of sample. RESULTS: A total of 9 studies were included in this study, including 1592 patients. The pooled sensitivity and specificity of D-dimer for PJI diagnosis are 0.82 (95% CI, 0.72~0.89) and 0.73 (95% CI, 0.58~0.83), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.99 (95% CI, 1.84~4.88) and 0.25 (95% CI, 0.15~0.41), respectively. The pooled AUC and diagnostic odds ratios were 0.85 (95% CI, 0.82~0.88) and 12.20 (95% CI, 4.98~29.86), respectively. CONCLUSION: D-dimer is a promising biomarker for the diagnosis of PJI, which should be used in conjunction with other biomarkers or as an adjunct to other diagnostic methods to enhance diagnostic performance.

The effect of posterior capsule repair in total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Prior studies have compared the posterior capsule repair group in primary total hip arthroplasty by posterior approach with the control group without posterior capsule repair suggesting that the posterior capsule repair group had better clinical outcomes. However, it is still a controversy which treatment is more helpful for hip diseases. The purpose of our article is to obtain the postoperative outcomes between the 2 procedures. METHODS: We performed a systematic search by browsing the MEDLINE, EMBASE, Cochrane Library. There is no restriction on the date of publication. Before we submit our manuscript, we have re-searched the literatures again, including the articles which directly compared the postoperative outcomes of the 2 procedures. RESULTS: A total of 8 comparative studies were included in our meta-analysis. The posterior capsule repair group showed less dislocation rate, higher HHS, and even less postoperative bleeding volume. Meanwhile, there is no significant difference in ROM between 2 groups. CONCLUSION: In conclusion, according to current evidences, repairing posterior capsule during primary THA may have better functional outcomes, less dislocation incidence, and less loss of blood.

Can nasal Staphylococcus aureus screening and decolonization prior to elective total joint arthroplasty reduce surgical site and prosthesis-related infections? A systematic review and meta-analysis.

BACKGROUND: Nasal Staphylococcus aureus (S. aureus) screening and decolonization has been widely used to reduce surgical site infections (SSIs) prior to total knee and hip arthroplasty (TKA and THA). However, it remains considerably controversial. The aim of this study was to ascertain whether this scheme could reduce SSIs and periprosthetic joint infections (PJIs) following elective primary total joint arthroplasty (TJA). METHODS: A systematic search was performed in MEDLINE, Embase, and the Cochrane Library until October, 2019. Outcomes of interest included SSI, PJI, superficial infection, and different bacterial species that caused infections. Data from eligible studies were then extracted and synthesized. Pooled odds ratios (OR) and 95% confidence intervals (CIs) were calculated. We also performed additional analyses to evaluate whether there were differences in postoperative SSIs caused by S. aureus or other bacteria. RESULTS: Nine studies were included in our meta-analysis. The pooled data elucidated that nasal S. aureus screening and decolonization dramatically mitigated the risk of SSI, PJI, and superficial infection compared to nondecolonization group. The analysis of bacterial species causing infection also showed that the S. aureus infections postoperative were significantly decreased in the decolonization group. However, there was no statistical difference in the SSI caused by other bacteria between the two groups. CONCLUSION: S. aureus screening and decolonization prior to elective primary THA and TKA could significantly decrease the risk of SSI and PJI. However, more robust studies are needed to further evaluate the impact of S. aureus screening and decolonization on infection risk after TJA.

Ubiquitin-specific peptidase 22 promotes proliferation and metastasis in human colon cancer.

Colon cancer is one of the most common malignant tumors in the world; however, the mechanism underlying the progression of colon cancer remains unclear. In the present study, the expression of ubiquitin-specific peptidase 22 (USP22) in paraffin sections of human colon cancer tissues and normal colon tissues were examined using immunohistochemistry. The human colon cancer cell lines HCT116 and HT29 were used for USP22 knockdown experiments, and functional assays were performed. The results demonstrated that compared with normal colon tissues, human colon cancer tissues exhibited upregulated expression of USP22 and this was associated with tumor lymph node metastasis and tumor stage in colon cancer tissues. In addition, upregulated expression of USP22 was significantly correlated with both lower relapse-free survival and lower overall survival rates in patients with colon cancer. When USP22 was silenced in colon cancer cell lines, this resulted in a decrease in cell proliferation and metastatic behaviors. Furthermore, Bmi-1 and Cyclin D2 were found to be positively regulated by USP22, which may have mediated the tumorigenic effects of USP22 in human colon cancer. The results of the present study may have significant implications for examining the underlying mechanisms of cancer development and the potential development of cancer therapeutics.

Resveratrol Induces Endothelial Progenitor Cells Angiogenesis via MiR-542-3p by Targeting Angiopoietin-2 and Involves in Recanalization of Venous Thrombosis.

BACKGROUND Endothelial progenitor cells (EPCs) play an important role in therapeutic angiogenesis. Besides, resveratrol (RSV) exerts many pharmacological functions in regulation of cell function. Furthermore, microRNAs (miRNAs) have been considered to be of great significance in biological process. In this study, we aimed to investigate the effect of RSV on EPCs and its potential mechanism that involved in recanalization of venous thrombosis. MATERIAL AND METHODS EPCs were treated with RSV, and angiogenic functions was evaluated by tube formation and migration assays. miR-542-3p expression level in EPCs was assessed and exogenously modified. Bioinformatic analysis was applied to detect the potential target of miR-542-3p. Effects of RSV treatment in vivo venous thrombosis rat model were evaluated. RESULTS RSV enhanced angiogenic function of EPCs and decreased expression of miR-542-3p. Dual luciferase reporter gene and western blot results confirmed angiopoietin-2 (ANGPT2) was a direct target of miR-542-3p. It was found that inhibition of miR-542-3p contributed to angiogenesis of EPCs and elevated ANGPT2 protein level. Finally, in a rat model of venous thrombosis, RSV-treated EPCs promoted recanalization of thrombi. CONCLUSIONS We demonstrated that RSV can contribute to progenitor cells angiogenesis via miR-542-3p by targeting ANGPT2, subsequently enhanced recanalization of thrombi.

MiR-150 promotes angiogensis and proliferation of endothelial progenitor cells in deep venous thrombosis by targeting SRCIN1.

Venous thromboembolism (VTE), encompassing deep venous thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease. miR-150 is one of important microRNAs which play critical role in various cellular function such as endothelial progenitor cells (EPCs). In this study, we investigate the effect of miR-150 on EPCs function ex vivo and thrombus resolution in vivo. We determined miR-150 expression in EPCs isolated from DVT patients and control subjects by RT-PCR. Potential target of miR-150 was confirmed by bioinformatics analysis and luciferase reporter respectively. The angiogenesis and proliferation were tested by MTT and tube formation assay. A murine model of venous thrombosis was developed as in vivo model. Finally, the effect of miR-150 on EPCs with inferior venous thrombosis were evaluated in vivo. Our data showed that miR-150 was downregulated in EPCs from DVT patients. By using miR-150 agomir and antagomir, we found that miR-150 promoted angiogenesis and proliferation of EPCs. Bioinformatics analysis revealed SRCIN1 as a target of miR-150 and SRCIN1 knockdown inhibited function of EPCs. Forced expression of miR-150 contributed thrombus resolution in a murine model of venous thrombosis. In general, miR-150 was downregulated in EPCs from DVT. Upregulation of miR-150 promoted angiogenesis and proliferation of EPCs by targeting SRCIN1 in vitro and thrombus resolution in vivo.

Systematic Review and Meta-Analysis of Iliofemoral Stenting for Post-thrombotic Syndrome.

OBJECTIVE: Stent placements are considered as a treatment for post-thrombotic syndrome (PTS) with iliofemoral obstruction, but the application of these iliofemoral venous stents has also caused a lot of controversy. The purpose of this systematic review and meta-analysis was to summarise the efficacy and safety of venous stents in PTS with obstruction in iliofemoral venous segments. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register for Controlled Trials databases and key references were searched up to 15 January 2018. The main relevant outcomes included technical success, peri-operative complications, symptom resolution, a change of symptom scores, and long-term patency of the stents. RESULTS: Overall, 504 limbs of 489 patients from seven studies were included in this study. A GRADE assessment showed the quality of the evidence was "very low" for 11 relevant outcomes. The technical success rate was 95%. The pooled rate of complications including 30 day thrombotic event, per-operative venous injury, and back pain was 3.4%, 18.14%, and 52%, respectively. The rates of ulcer healing, pain and oedema relief were 75.66%, 52%, and 42%, respectively. The primary, assisted primary and secondary patency rates were 83.36%, 90.59%, and 94.32%, respectively, at 12 months and 67.98%, 82.26%, and 86.10%, respectively, at 36 months. CONCLUSIONS: Endovenous stenting has the potential to be effective and has a low risk of peri-operative complications. The quality of evidence to support this treatment is very low. Endovenous iliofemoral stenting should be considered a treatment option for PTS with iliofemoral obstruction.

Human cancer cells suppress behaviors of endothelial progenitor cells through miR-21 targeting IL6R.

Deep vein thrombosis (DVT) is a severe clinical process and has a high rate of fatality. Cancer patients have a high incidence rate of venous thrombosis complication and increase the mortality of cancer patients for 2-8 times. The mechanisms involved in human cancers and venous thrombosis remains unclear. In this study, we determined miR-21 expressed higher in human breast cancer, colon cancer and hepatocellular cancer tissues compared with normal tissues and expressed higher in exosomes of breast cancer and hepatocellular cancer cell lines compared with normal cells. MiR-21 dramatically suppressed proliferation, migration and invasion of endothelial progenitor cells (EPCs), which performed promoting role in thrombus repairment and resolution. High levels of miR-21 in exosomes of human cancers dramatically inhibited behaviors of EPCs, and depletion of miR-21 abrogated the decreased proliferation, migration and invasion of EPCs induced by human cancer cells. Moreover, IL6R (interleukin 6 receptor) was identified to be a direct target of miR-21 and promoted cell proliferation, migration and invasion of EPCs. Therefore, the miR-21-IL6R pathway contributed to behaviors of EPCs and consequently mediated the vein thrombosis in patients with cancer. MiR-21-IL6R pathway based therapeutic methods would be beneficial to decrease the complicated venous thrombosis in cancer patients and promote thrombus resolution.

Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma.

Osthole is a natural coumarin isolated from Umbelliferae plant monomers. Previous research has indicated that osthole exerts a wide variety of biological effects, acting as anti-seizure, anti-osteoporosis and anti-inflammation. However, the regulatory effect and related molecular mechanism of osthole in intrahepatic cholangiocarcinoma (ICC) remain unknown. In the present study, the authors found that osthole inhibited ICC cell lines in a dose- and time-dependent manner. Osthole also significantly induced mitochondrial-dependent apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9, and cleaved poly ADP-ribose polymerase expression, and by downregulating Bcl-2 expression. Moreover, the levels of p-Akt and PI3K were significantly decreased, while total Akt protein levels were unchanged. Following transfection with wild-type-Akt and constitutively active (CA)-Akt plasmids, the effects of osthole were decreased. Osthole was also able to suppress tumor growth in vivo. Together, these data demonstrated that osthole induces mitochondrial-dependent apoptosis via the PI3K/Akt pathway, suggesting that osthole may represent a novel and effective agent for the treatment of ICC.

Modulatory role of garlicin in migration and invasion of intrahepatic cholangiocarcinoma via PI3K/AKT pathway.

Increasing evidences have indicated the role of garlicin in inhibiting the progression of various tumors including glioma, pulmonary carcinoma and pancreatic carcinoma, via mediating cell apoptosis or cell cycle. The regulatory effect and related molecular mechanism of garlicin in intrahepatic cholangiocarcinoma, however, remained unknown. This study thus aimed to investigate this scientific issue. HCCC-9810 cell line was treated with serially diluted garlicin, followed by cell proliferation assay using MTT approach. Transwell migration and invasion assays were further employed the regulatory effect of garlicin. The expression level of p-AKT and AKT proteins in tumor cells was quantified by Western blot. The growth of tumor cells was significantly inhibited by high concentration of garlicin (> 1.5 µM). Lower concentration of garlicin showed dose-dependent inhibition of tumor cell invasion and migration. After using specific agonist IGF-1 (50 ng/mL) of PI3K/AKT signaling pathway, such facilitating effects of garlicin were depressed (P < 0.05). Western blotting showed significantly decreased phosphorylation level of AKT after treated with gradient concentrations of garlicin, while leaving the total AKT protein level unchanged. Garlicin may inhibit the invasion and migration of intrahepatic cholangiocarcinoma cells via inhibiting PI3K/AKT signaling pathway.