Recent epidemiological studies have demonstrated that metformin lowers the risk of several types of cancer in diabetic patients. Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the vascular basement membrane extracellular matrix proteins, thereby promoting endothelial cell invasion, migration and angiogenesis in the incidence and progression of tumors. The aim of this study was to investigate the effects of metformin on human umbilical vein endothelial cell (HUVEC) proliferation and migration, as well as on MMP-2 and MMP-9 expression. Cell proliferation was determined by cell counting and MTT colorimetric assays. Cell migration was assessed by the wound repair method. Quantitative real-time reverse transcription PCR was performed to quantify the mRNA expression of MMPs. Metformin at concentrations of 0.5–3.0 mM effectively reduced the number of endothelial cells by 5.5–55%, without being cytotoxic to the cells. Similarly, cell proliferation and migration were markedly inhibited by metformin. In addition, treatment with metformin demonstrated a strong (P<0.001) suppressive effect on the mRNA levels of MMP-2 and -9 in the endothelial cells. The inhibitory effects of metformin on endothelial cell number, migration, and MMP expression were reversed partially by compound C, which is an inhibitor of AMP-activated protein kinase (AMPK). The present study reports that metformin considerably inhibited the proliferation, migration, and MMP-2 and -9 expression of HUVECs, and the effect was partially AMPK-dependent. The obtained findings provide a molecular rationale, whereby metformin can exert anticancer effects.
Study Objectives: Opioids have been reported to increase the risk for sleep-disordered breathing (SDB) in patients with noncancer chronic pain on opioid therapy. This study aims to determine the pooled prevalence of SDB in opioid users with chronic pain and compare it with patients with pain:no opioids and no pain:no opioids. Methods: A literature search of PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials was conducted. We included all observational studies that reported the prevalence of SDB in patients with chronic pain on long-term opioid therapy (≥3 months). The primary outcome was the pooled prevalence of SDB in opioid users with chronic pain (pain:opioids group) and a comparison with pain:no opioids and no pain:no opioids groups. The meta-analysis was performed using a random-effects model. Results: After screening 1,404 studies, 9 studies with 3,791 patients were included in the meta-analysis (pain:opioids group, n = 3181 [84%]; pain:no opioids group, n = 359 [9.4%]; no pain:no opioids group, n = 251 [6.6%]). The pooled prevalence of SDB in the pain:opioids, pain:no opioids, and no pain:no opioids groups were 91%, 83%, and 72% in sleep clinics and 63%, 10%, and 75% in pain clinics, respectively. Furthermore, in the pain: opioids group, central sleep apnea prevalence in sleep and pain clinics was 33% and 20%, respectively. Conclusions: The pooled prevalence of SDB in patients with chronic pain on opioid therapy is not significantly different compared with pain:no opioids and no pain:no opioids groups and varies considerably depending on the site of patient recruitment (ie, sleep vs pain clinics). The prevalence of central sleep apnea is high in sleep and pain clinics in the pain:opioids group. Clinical Trial Registration: Registry: PROSPERO: International prospective register of systematic reviews; Name: Prevalence of sleep disordered breathing, hypoxemia and hypercapnia in patients on oral opioid therapy for chronic pain management; URL: https://www.crd.york.ac.uk/prospero/display_record.php?
Background: As of the potential immunomodulatory effects of interleukin-4 (IL-4) and its importance in
BACKGROUND: Proinfl ammatory cytokines have been known to play a considerable part in the pathomechanisms of chronic heart failure (CHF). Given the importance of proinfl ammatory cytokines in the context of the failing heart, we assessed whether the polymorphisms of interleukin (IL)-1 gene cluster, including IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1RA) and IL-1R gene are predictors of CHF due to ischemic heart disease. METHODS: Forty-three patients with ischemic heart failure were recruited in this study as patients group and compared with 140 healthy unrelated control subjects. Using polymerase chain reaction with sequence-specifi c primers method, the allele and genotype frequency of 5 single nucleotide polymorphisms (SNPs) within the IL-1α (-889), IL-1β (-511, +3962), IL-1R (psti 1970), and IL-1RA (mspa1 11100) genes were determined. RESULTS: The frequency of the IL-1β-511/C allele was signifi cantly higher in the patient group compared to that in the control group (p = 0.031). The IL-1β (-511) C/C genotype was signifi cantly overrepresented in patients compared to controls (p = 0.022). CONCLUSIONS: Particular allele and genotype in IL-1β gene were overrepresented in patients with ischemic heart failure, possibly affecting the individual susceptibility to this disease (Tab. 1, Ref. 27).
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