Revealing the pharmacological mechanisms of nao-an dropping pill in preventing and treating ischemic stroke via the PI3K/Akt/eNOS and Nrf2/HO-1 pathways.

Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth.

BACKGROUND: While colorectal polyps are not cancerous, some types of polyps, known as adenomas, can develop into colorectal cancer over time. Polyps can often be found and removed by colonoscopy; however, this is an invasive and expensive test. Thus, there is a need for new methods of screening patients at high risk of developing polyps. AIM: To identify a potential association between colorectal polyps and small intestine bacteria overgrowth (SIBO) or other relevant factors in a patient cohort with lactulose breath test (LBT) results. METHODS: A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology. SIBO was diagnosed by measuring LBT-derived hydrogen (H) and methane (M) levels according to 2017 North American Consensus recommendations. Logistic regression was used to assess the ability of LBT to predict colorectal polyps. Intestinal barrier function damage (IBFD) was determined by blood assays. RESULTS: H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group (41% vs 23%, P < 0.01; 71% vs 59%, P < 0.05, respectively). Within 90 min of lactulose ingestion, the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group (P < 0.01, and P = 0.03, respectively). In 227 patients with SIBO defined by combining H and M values, the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without (15% vs 5%, P < 0.05). In regression analysis with age and gender adjustment, colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO. These models had a sensitivity of ≥ 0.67, a specificity of ≥ 0.64, and an accuracy of ≥ 0.66. CONCLUSION: The current study made key associations among colorectal polyps, SIBO, and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

GP73 enhances the ox-LDL-induced inflammatory response in THP-1 derived macrophages via affecting NLRP3 inflammasome signaling.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease with its molecular basis incompletely understood. Here, we determined whether the Golgi phosphoprotein 73 (GP73), a novel protein highly related to inflammation and disrupted lipid metabolism, was involved in the development of atherosclerosis. METHODS: Public microarray databases of human vascular samples were analyzed for expression patterns. Apolipoprotein-E-gene-deficient (ApoE-/-) mice (8-week-old) were randomly assigned to either a chow diet group or a high-fat diet group. The levels of serum GP73, lipid profiles and key inflammatory cytokines were determined by ELISA. The aortic root plaque was isolated and used for by Oil Red O staining. PMA-differentiated THP-1 macrophages were transfected with GP73 small interfering RNA (siRNA) or infected with adenovirus expressing GP73, and then stimulated with oxidized low density lipoprotein (ox-LDL). The expressions of pro-inflammatory cytokines and signal pathway key targets were determined by ELISA kit and Western blot respectively. In addition, ichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to measure the intracellular ROS levels. RESULTS: The expressions of GP73 and NLRP3 were substantially upregulated in human atherosclerotic lesions. There were significant linear correlations between GP73 and inflammatory cytokines expressions. High-fat diet-induced atherosclerosis and increased levels of plasma inflammatory mediators (IL-1ß, IL-18, and TNF-α) were observed in ApoE-/- mice. Besides, the expressions of GP73 in the aorta and serum were significantly upregulated and positively correlated with the NLRP3 expression. In the THP-1 derived macrophages, ox-LDL treatment upregulated the expressions of GP73 and NLRP3 proteins and activated the inflammatory responses in a concentration-dependent and time-dependent manner. Silencing of GP73 attenuated the inflammatory response and rescued the decreased migration induced by ox-LDL, inhibiting the NLRP3 inflammasome signaling and the ROS and p-NF-κB activation. CONCLUSIONS: We demonstrated that GP73 promoted the ox-LDL-induced inflammation in macrophages by affecting the NF-κB/NLRP3 inflammasome signaling, and may play a role in atherosclerosis.

Long-term efficacy and safety of cap-assisted endoscopic sclerotherapy with long injection needle for internal hemorrhoids.

BACKGROUND: Hemorrhoids are a common anal condition and can afflict an individual at any age. Epidemiological survey results in China show that the prevalence of anorectal diseases is as high as 50.1% among which 98.08% of patients have hemorrhoid symptoms. AIM: To assess long-term efficacy and safety of cap-assisted endoscopic sclerotherapy (CAES) with long injection needle for internal hemorrhoids. METHODS: This study was retrospective. Data from patients with symptomatic internal hemorrhoids treated with CAES using endoscopic long injection needle from April 2016 to December 2019 were collected. Patients were telephoned and followed at two time points, December 2020 and 2021, to evaluate the improvements in symptoms, complications, recurrence, and satisfaction. RESULTS: Two hundreds and one patients with internal hemorrhoids underwent CAES with the long needle. The first median follow-up was performed 33 mo post-operatively. Symptoms improved in 87.5% of patients after the first CAES. Efficacy did not decrease with treatment time extension. Fifty-four patients underwent colonoscopy after the first CAES treatment of which 21 underwent CAES again, and 4 underwent hemorrhoidectomy. At the first follow-up, 62.7% of patients had both improved hemorrhoid grades and symptoms, and 27.4% had a significant improvement in both parameters. At the second follow-up, 61.7% of the patients showed satisfactory improvement in their hemorrhoid grade and symptoms when compared with pre-surgery values. 90% of patients reported CAES was painless, and 85% were satisfied/very satisfied with CAES treatment outcomes. CONCLUSION: The present study based on the largest sample size reported the long-term follow-up of the treatment for internal hemorrhoid with the CAES using endoscopic long injection needle. Our findings demonstrate that CAES should be a micro-invasive endoscopic technology yields satisfactory long-term efficacy and safety.

CIDEC: A Potential Factor in Diabetic Vascular Inflammation.

Cell death-inducing DFF45-like effector C (CIDEC) is involved in diet-induced adipose inflammation. Whether CIDEC plays a role in diabetic vascular inflammation remains unclear. A type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated its characteristics by metabolic tests, Western blot analysis of CIDEC and C1q/tumor necrosis factor-related protein-3 (CTRP3) expression, and histopathological analysis of aortic tissues. The diabetic group exhibited elevated CIDEC expression, aortic inflammation, and remodeling. To further investigate the role of CIDEC in the pathogenesis of aortic inflammation, gene silencing was used. With CIDEC gene silencing, CTRP3 expression was restored, accompanied with amelioration of insulin resistance, aortic inflammation, and remodeling in diabetic rats. Thus, the silencing of CIDEC is potent in mediating the reversal of aortic inflammation and remodeling, indicating that CIDEC may be a potential therapeutic target for vascular complications in diabetes.

Prolonged flushing and locking interval for totally implantable vascular access device: A systematic review and meta-analysis.

The objective of this systematic review is to evaluate the safety ad feasibility of the totally implantable vascular access devices (TIVADs) flushed more than 4 weeks. We searched the following electronic databases from the date their build-up to February 2020: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL. The final selection resulted in 14 trials fulfilling the inclusion criteria and being included in our review. A pooled frequency of port-related late complications with longer flushing intervals (>4 weeks) was 8.0%, and the pooled frequency of occlusions, infections, and mechanical complications was 5.0%, 2.0%, and 3.0%, respectively. Then, we compared the frequency of port-related complications between standard and longer flushing intervals. There were no differences between the group's changes in the frequency of total late complications, occlusions, infections, and mechanical complications. This systematic review and meta-analysis demonstrates that longer flushing intervals for ports are safe. However, more prospective, power appropriated randomized trials are needed to explore the specific flushing time for ports.

Mitochondria autophagy: a potential target for cancer therapy.

Mitophagy is a selective form of macroautophagy in which dysfunctional and damaged mitochondria can be efficiently degraded, removed and recycled through autophagy. Selective removal of damaged or fragmented mitochondria is critical to the functional integrity of the entire mitochondrial network and cells. In past decades, numerous studies have shown that mitophagy is involved in various diseases; however, since the dual role of mitophagy in tumour development, mitophagy role in tumour is controversial, and further elucidation is needed. That is, although mitophagy has been demonstrated to contribute to carcinogenesis, cell migration, ferroptosis inhibition, cancer stemness maintenance, tumour immune escape, drug resistance, etc. during cancer progression, many research also shows that to promote cancer cell death, mitophagy can be induced physiologically or pharmacologically to maintain normal cellular metabolism and prevent cell stress responses and genome damage by diminishing mitochondrial damage, thus suppressing tumour development accompanying these changes. Signalling pathway-specific molecular mechanisms are currently of great biological significance in the identification of potential therapeutic targets. Here, we review recent progress of molecular pathways mediating mitophagy including both canonical pathways (Parkin/PINK1- and FUNDC1-mediated mitophagy) and noncanonical pathways (FKBP8-, Nrf2-, and DRP1-mediated mitophagy); and the regulation of these pathways, and abovementioned pro-cancer and pro-death roles of mitophagy. Finally, we summarise the role of mitophagy in cancer therapy. Mitophagy can potentially be acted as the target for cancer therapy by promotion or inhibition.

G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3ß and stabilizing ß-catenin.

Ras-GTPase activating SH3 domain-binding protein 1 (G3BP1) is a multifunctional binding protein involved in the development of a variety of human cancers. However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer. Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulating ß-catenin signaling, which upregulates a number of proliferation-related genes. We further show that G3BP1 improves the stability of ß-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription of ß-catenin. Mechanistically, elevated G3BP1 interacts with and inactivates GSK-3ß to suppress ß-catenin phosphorylation and degradation. Disturbing the G3BP1-GSK-3ß interaction accelerates the degradation of ß-catenin, impairing the proliferative capacity of breast cancer cells. Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3ß/ß-catenin axis may be a potential therapeutic target for breast cancer.

A systematic review of guidelines for dual antiplatelet therapy in coronary artery bypass graft.

BACKGROUND: In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice. METHODS AND RESULTS: Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than 'applicability'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery. CONCLUSIONS: Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.

Anti-adipogenicadamantane type polycyclic polyprenylated acylphloroglucinols from Hypericum subsessile.

Hypersubones D-H (1-5), five new polycyclic polyprenylated acylphloroglucinols (PPAPs) type metabolites with intriguing adamantane and homo-adamantane skeletons, were characterized from aerial parts of Hypericum subsessile. Compounds 1-2 were elucidated to share an adamantane core with 28,29-expoxide moiety, while 3-5 were homo-adamantane type PPAPs sharing a1,2-dioxepane ring system. Their structures were determined on the basis of comprehensive NMR and MS spectroscopic data.The anti-adipogenesis activities of these isolates were evaluated through employing 3T3-L1 cells as an in vitro system using oil red O staining, and compounds 1, 2 and 5 were able to significant inhibit the adipocyte differentiation, which implied that these compounds possessed anti-adipogenic activity.

Transgelin interacts with PARP1 in human colon cancer cells.

BACKGROUND: Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that transgelin was up-regulated in node-positive colorectal cancer (CRC) versus node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms through which transgelin participates in the metastasis of colon cancer cells. METHODS: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with transgelin. The 256 downstream transcripts regulated by transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with transgelin. The interaction between transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence. RESULTS: Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven key genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1, which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with transgelin. The interaction between PARP1 and transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays. CONCLUSIONS: Our results suggest that transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.

Testosterone ameliorates vascular aging via the Gas6/Axl signaling pathway.

Low serum testosterone level is associated with aging-related vascular stiffness, but the underlying mechanism is unclear. The Growth arrest-specific protein 6 (Gas6) /Axl pathway has been proved to play important roles in cell senescence. In this study, we intend to explore whether Gas6/Axl is involved in the effect of testosterone on vascular aging amelioration. Vascular aging models of wild type and Axl-/- mice were established by natural aging. Mice of these two gene types were randomized into young group, aging group and testosterone undecanoate (TU) treatment group. Mice were treated with TU (37.9 mg/kg) in the TU group, which treated with solvent reagent served as control. The aging mice exhibited decreases in serum testosterone, Gas6 and Axl levels and an increase in cell senescence, manifested age-related vascular remodeling. Testosterone treatment induced testosterone and Gas6 levels in serum, and ameliorated cell senescence and vascular remodeling in aging mice. Furthermore, we uncover the underlying molecular mechanism and show that testosterone treatment restored the phosphorylation of Akt and FoxO1a. Axl knockout accelerated cell senescence and vascular remodeling, and resisted the anti-aging effect of testosterone. Testosterone might exert a protective effect on vascular aging by improving cell senescence and vascular remodeling through the Gas6/Axl pathway.

Correction to: Eriocalyxin B Inhibits Adipogenesis in 3T3­L1 Adipocytes by Cell Cycle Arrest.

In the original publication of this article, we found an error under the section "Introduction". The first sentence of the fourth paragraph appears incorrectly. The corrected sentence is given below. Eriocalyxin B, isolated and identified in 1982 [1], is the major component in Chinese plant Isodon eriocalyx (Dunn.) Hara (family Lamiaceae) showing many pharmacological activities, such as inhibiting inflammatory response, regulating immune cell differentiation, inhibiting tumor cells proliferation, causing cell cycle arrest affecting angiogenesis and promoting cancer cells apoptosis.

Adipogenesis Inhibitory Activity of Hypersampsone P from Hypericum subsessile.

Adamantane polycyclic polyprenylated acylphloroglucinols (PPAPs) with caged architecture, a special class of hybrid natural products, is specifically rich in the plant family Guttiferae, especially Hypericum or Garcinia genus. Hypersampsone P is one of Adamantane PPAPs compounds extracted from Hypericum subsessile. Here we have chosen, screened ten PPAPs and identified one of them showed an activity in inhibiting of adipocytes differentiation. Particularly, the compound, hypersampsone P, blunted the adipocyte differentiation dose-dependently. Moreover, hypersampsone P down-regulated the expressions of several key regulators for adipogenesis, including PPARγ and FABP4. The treatment of cells at the early stage of adipogenesis by hypersampsone P induced the greatest blunting of adipocyte differentiation and the effect might be involved in the LKB1-AMPK signaling pathway.

Eriocalyxin B Inhibits Adipogenesis in 3T3-L1 Adipocytes by Cell Cycle Arrest.

Eriocalyxin B, an ent-Kaurene diterpenoid extracted from a traditional Chinese herb Isodon eriocalyx, has been shown to possess multifunctional activities such as anti-cancer and anti-inflammatory. However, the function and mechanism of the compound in adipocyte differentiation is still unknown. Here we reported that eriocalyxin B blunted adipogenesis remarkably by inhibiting the accumulation of lipid droplets, triglycerides and the expressions of adipogenesis-related factors, including C/EBPß, C/EBPα, PPARγ, and FABP4. Moreover, we showed that the inhibition might be the consequence of cell cycle being arrested at the G2/M phase during the mitotic clonal expansion of adipocyte differentiation, most likely by suppressing mRNAs and proteins of CDK1, CDK2, Cyclin A and Cyclin B1. Overall, we conclude that eriocalyxin B is capable of inhibiting adipocyte differentiation at the early stage through downregulating the proteins involved in cell cycle progression.

Steaming Changes the Composition of Saponins of Panax notoginseng (Burk.) F.H. Chen That Function in Treatment of Hyperlipidemia and Obesity.

Saponins of Panax notoginseng (Burk.) F.H. Chen have been classified as a type of composition in functional foods for numerous diseases. However, its mild effects and other characteristics limited clinical applications in diseases. Inspired by "nine steaming and nine processing" of P. notoginseng in traditional Chinese medicine, we developed a "steaming"-mimic protocol, which significantly changed the composition of saponins of P. notoginseng from the original, R1, Rg1, Re, Rb1, and Rd (raw-PNS), to the products after steaming, 20S/R-Rh1, Rk3, Rh4, 20S/R-Rg3, Rk1, and Rg5 (N-PNS). Surprisingly, N-PNS demonstrated promising activities in improving hyperlipidemia and reducing body weight and weight of white adipose tissue and the inhibition of adipogenesis in obese mice. In accordance with the results in vivo, N-PNS remarkably blunted adipogenesis at the early stage of differentiation dose-dependently in vitro. Moreover, we demonstrated that the activity may involve the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway by promoting phosphorylation of AMPKT172 and downregulating its downstream factors: sterol regulatory element binding protein 1c, stearoyl-CoA desaturase 1, and fatty acid synthase. Taken together, the steaming-induced eight compositions of saponins showed a very promising function in improving hyperlipidemia and obesity both in vivo and in vitro, providing fundamental evidence for future study and application in treatment of hyperlipidemia, obesity, and other lipid-related metabolic syndromes.

Cell death-inducing DFF45-like effector C gene silencing alleviates pulmonary vascular remodeling in a type 2 diabetic rat model.

AIMS/INTRODUCTION: Cell death-inducing DFF45-like effector C (CIDEC) was proven to be closely associated with the development of insulin resistance and metabolic syndrome. We aimed to investigate whether CIDEC gene silencing could alleviate pulmonary vascular remodeling in a type 2 diabetes rat model. MATERIALS AND METHODS: We built a type 2 diabetes rat model. An adenovirus harboring CIDEC small interfering ribonucleic acid was then injected into the jugular vein to silence the CIDEC gene. After hematoxylin-eosin and Sirius red staining, we detected indexes of the pulmonary arterioles remodeling. Immunohistochemical staining of proliferating cell nuclear antigen was used to evaluate the pulmonary arterial smooth muscle cell proliferation. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling reaction and western blotting. The levels of signaling pathway proteins expression were measured by western blotting analyses. RESULTS: Histological analysis of the pulmonary artery showed that the thickness of the adventitia and medial layer increased notably in type 2 diabetes rats. Immunohistochemistry showed that more proliferating cell nuclear antigen-positive pulmonary arterial smooth muscle cells could be seen in type 2 diabetes rats; and after CIDEC gene silencing, proliferating cell nuclear antigen positive cells decreased accordingly. Cleaved caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase measured by western blotting showed increased apoptosis with overexpressed CIDEC in diabetes. Terminal deoxynucleotidyl transferase dUTP nick end labeling reaction showed that the apoptosis mainly occurred in endothelial cells. Western blotting analysis showed CIDEC overexpression in rats with diabetes, and phosphorylated adenosine 5' monophosphate-activated protein kinase-α expression was significantly decreased. After CIDEC gene silencing, the expression of phosphorylated adenosine 5' monophosphate-activated protein kinase-α was upregulated. CONCLUSIONS: The CIDEC/5' monophosphate-activated protein kinase signaling pathway could be a potential therapeutic candidate against pulmonary vascular diseases in type 2 diabetes patients.

Efficacy, safety and influencing factors of intra-calf muscular injection of bone marrow mononuclear cells in the treatment of type 2 diabetes mellitus-induced lower extremity vascular disease.

The efficacy, safety and impact of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) associated with the intra-calf muscular injection of bone marrow mononuclear cells (BMMCs) in the treatment of type 2 diabetes mellitus (T2DM)-induced lower extremity vascular disease (LEVD) were evaluated. Patients with T2DM-LEVD were randomly divided into a control group and BMMCs group to assess the efficacy and safety of the treatment; serum VEGF and bFGF levels were detected. The BMMCs group was divided into superior genicular artery (SGA) and inferior genicular artery (IGA) subgroups as well as low-dose and high-dose subgroups for the comparison of efficacy indices. The BMMCs group exhibited significantly improved indices (P<0.05) compared with the control group and no fatalities or cancer occurred. There were no significant changes in serum VEGF and bFGF levels (P>0.05). The claudication distance in the IGA subgroup was significantly greater that in the SGA subgroup (P<0.05); the low-dose subgroup and the high-dose subgroup did not demonstrate any significant differences in each index (P>0.05). BMMC treatment for T2DM-LEVD was found to be safe and effective and had no significant impact on serum VEGF and bFGF levels in the short term; However, the degree of LEVD may affect its efficacy.

Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.

BACKGROUND: Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by determining whether experimental manipulation of transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo. METHODS: Isogenic CRC cell lines that differ in transgelin expression were characterized using in vitro assays of growth and invasiveness and a mouse tail vein assay of experimental metastasis. Downstream effects of transgelin overexpression were investigated by gene expression profiling and quantitative PCR. RESULTS: Stable overexpression of transgelin in RKO cells, which have low endogenous levels, led to increased invasiveness, growth at low density, and growth in soft agar. Overexpression also led to an increase in the number and size of lung metastases in the mouse tail vein injection model. Similarly, attenuation of transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model. Investigation of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts, with over-representation of genes that affect function of actin or other cytoskeletal proteins. Changes included increases in HOOK1, SDCCAG8, ENAH/Mena, and TNS1 and decreases in EMB, BCL11B, and PTPRD. CONCLUSIONS: Increases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes.