RESUMEN

Plasma proteins are promising biomarkers and potential drug targets for stroke. This study aimed to explore whether there is a causal relationship between plasma proteins and subtypes of stroke using a Mendelian randomization (MR) approach. A two-sample bidirectional Mendelian randomization approach was employed to investigate the causal link between plasma proteins and stroke. Data on plasma proteins were obtained from three studies, including INTERVAL, and pooled stroke information was sourced from the MEGASTROKE consortium and the UK Biobank dataset, covering four subtypes of stroke. MR analyses were primarily conducted using inverse variance weighting, and sensitivity analyses were also performed. Finally, potential reverse causality was assessed using bidirectional MR. We identified two proteins causally associated with stroke: one as a potential therapeutic target and another as a protective factor. CXCL8 was found to be positively associated with the risk of developing large-artery atherosclerotic (LAA) stroke (OR, 1.005; 95% CI 1.001 to 1.010; p = 0.022), whereas TNFRSF11b was negatively correlated with the risk of developing LAA stroke (OR, 0.937; 95% CI 0.892 to 0.984; p = 0.010), independently of other stroke subtypes. Reverse bivariate analysis did not indicate that ischemic stroke was causally associated with CXCL8 and TNFRSF11b. There is a causal relationship between CXCL8 and TNFRSF11b with LAA stroke, independent of other subtypes. This study offers a new perspective on the genetics of stroke.

RESUMEN

Background: Migraine is a prevalent neurovascular headache disorder. The link between dietary potassium and blood pressure has been established. We sought to delineate the relationship between dietary potassium intake and the prevalence of migraines. Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2004, comprising 10,254 participants aged ≥20 years. Participants who reported severe headaches or migraine in the self-report questionnaire were identified as migraineurs. A 24-h dietary recall methodology was used to assess dietary potassium intake. Multivariate regression analysis and restricted cubic spline (RCS) modeling were utilized to elucidate the relationship between dietary potassium and migraines. Results: Among the 10,254 participants, 20.1% were identified with migraine or severe headaches. The adjusted odds ratio (OR) for migraine occurrence in the Q2 dietary potassium intake (1771-2,476 mg/d) was 0.84 (95% CI: 0.73-0.97, p = 0.021) compared to the lowest quartile (Q1, ≤ 1771 mg/d). The relationship between dietary potassium and migraine exhibited an L-shaped pattern (non-linear, p = 0.016) with an inflection at approximately 1439.3 mg/d. In the subgroup analysis, when compared to Q1, who had the lowest dietary potassium intake, the adjusted OR for Q2 in females, those in the medium-high household income group, and with a Body Mass Index (BMI) ≥ 25 kg/m2 were as follows: (OR, 0.82; 95% CI, 0.69-0.98), (OR, 0.79; 95% CI, 0.66-0.95), and (OR, 0.78; 95% CI, 0.66-0.93), respectively. No significant interaction was observed across groups after adjusting for all possible covariates. Conclusion: The relationship between dietary potassium intake and migraine prevalence among US adults appears to follow an L-shaped curve.

RESUMEN

Bladder cancer has high morbidity and mortality rates among the male genitourinary system tumor types. MicroRNA­218 (miR­218) is associated with the development of a variety of cancer types, including bladder cancer. Rab6c is a member of the Rab family and is involved in drug resistance in MCF7 cells. The aim of the present study was to clarify the relationship between Rab6c and miR­218 in bladder cancer cell lines. In this study, the expression levels of miR­218 and Rab6c were evaluated via reverse transcription­quantitative PCR and western blotting, respectively. The association between Rab6c and miR­218 was recognized via TargetScan analysis and dual luciferase reporter gene detection. Cell proliferation was analyzed using Cell Counting Kit­8 and colony formation assays, and the invasive ability was measured via Transwell assays. Rab6c was highly expressed in bladder cancer, while miR­218 had abnormally low expression in bladder cancer. In addition, there was a mutual regulation between Rab6c and miR­218 in bladder cancer. It was found that overexpression of Rab6c significantly enhanced the proliferation, colony formation and invasion of T24 and EJ cells. Furthermore, miR­218 overexpression blocked the promoting effects of Rab6c on the malignant behavior of bladder cancer cells. Thus, Rab6c promotes the proliferation and invasion of bladder cancer cells, while miR­218 has the opposite effect, which may provide a novel insight for the treatment of bladder cancer.

Asunto(s)

RESUMEN

BACKGROUND & AIMS: The results of human clinical trials that have investigated the effects of resveratrol on blood pressure are inconsistent. We aimed to quantitatively evaluate the effects of resveratrol on systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: We conducted a strategic literature search of PubMed, EMBASE, MEDLINE, and the Cochrane Library (updated to January, 2014) for randomized controlled trials that evaluate the effects of resveratrol on SBP and DBP. Study quality was assessed using the Jadad scale. Weighted mean differences were calculated for net changes in SBP and DBP using fixed-effects or random-effects models. We performed pre-specified subgroup, sensitivity and meta-regression analyses to evaluate potential the heterogeneity. Dose effects of resveratrol on SBP and DBP were estimated using meta-regression analyses. RESULTS: Six studies comprising a total of 247 subjects were included in our meta-analysis. The overall outcome of the meta-analysis indicates that resveratrol consumption can not significantly reduce SBP and DBP. Subgroup analyses indicated that higher-dose of resveratrol consumption (≥ 150 mg/d) significantly reduces SBP of -11.90 mmHg (95% CI: -20.99, -2.81 mmHg, P = 0.01), whereas lower dose of resveratrol did not show a significant lowering effect on SBP. The meta-regression analyses did not indicate dose effects of resveratrol on SBP or DBP. CONCLUSIONS: The present meta-analysis indicates that resveratrol consumption significantly decreases the SBP level at the higher dose, while resveratrol has no significant effects on DBP levels. Additional high-quality studies are needed to further evaluate the causal conclusions.

Asunto(s)

RESUMEN

OBJECTIVE: To explore mechanism of S100A8 in the oncogenesis and development of laryngeal cancer. METHODS: Proteins interacting with S100A8 were isolated from laryngeal cancer cell lines Hep-2 by immunoprecipitation assay with anti-S100A8 antibody. The target bands were cut out and identified by maxtrix assisted laser desorption/ionization time of flight (MALDI-TOF). The peptide mass fingerprinting data of the proteins identified were analyzed based on the Mascot database. The NF-kappa B binding sites of the proteins were predicted by P-Match software. The binding ability of one of the proteins to S100A8 was confirmed by co-immunoprecipitation and immunocytochemistry methods. RESULTS: Four proteins interacting with S100A8 were obtained, which were hypothetical protein LOC80154, MHC class I HLA-B, similar to T-box 1 isoform C and sarcolemmal associated protein 1. The four genes were predicted to have NF-kappa B binding sites. MHC class I HLA-B, which is one of targets in NF-kappa B pathway, was first confirmed to have the binding ability to S100A8. CONCLUSION: The novel partners of S100A8 identified in the study might be involved in NF-kappa B pathway. The binding ability of MHC class I HLA-B to S100A8 implies that S100A8 might function as a new member with other proteins including HLA-B in NF-kappa B pathway. These findings provide a new clue to further study on the molecular mechanism of S100A8 in the genesis of laryngeal carcinomas.

Asunto(s)

RESUMEN

BACKGROUND: Laryngeal carcinoma is a common malignant tumor of the upper respiratory tract, and in 95% of cases the tumor is laryngeal squamous cell carcinoma (LSCC). The abnormity of SH3-domain GRB2-like 2 (SH3GL2) gene was found in LSCC. In order to clarify the relationship between SH3GL2 gene and LSCC, we evaluated the expression of the SH3GL2 gene in LSCC. METHOD: Real-time PCR, immunohistochemistry and Western blotting were used to detect the mRNA and protein expression and find the various rules of SH3GL2 gene in LSCC. RESULTS: The result of real-time PCR showed that the expression level of SH3GL2 mRNA in LSCC tissue was apparently down-regulated; immunohistochemical analysis showed that SH3GL2 protein was mainly located in cytoplasm, the rate of positive cells and SH3GL2 protein expression level were fluctuated with the pathological classification of LSCC; the result of Western blotting showed that SH3GL2 protein was down-regulated significantly in LSCC samples, especially in metastatic lymph nodes. CONCLUSIONS: These results suggest that SH3GL2 is a LSCC related gene and its expression level is fluctuated with the pathological classification which indicate that SH3GL2 participates in the development and progression of LSCC. And it may be considered as a novel tumor marker to find both a new anti-oncogene and relative factors of invasion and metastasis of laryngeal carcinoma.

Asunto(s)

RESUMEN

OBJECTIVE: With the objective of discovering novel putative chromosomal regions and special genes involved in the carcinogenesis, progression and metastasis of laryngeal squamous cell cancer (LSCC). METHODS: DNA copy profile of LSCC were obtained and analyzed by comparative genomic hybridization (CGH) and a computerized digital image analysis system. cDNA microarray of LSCC was performed and the profile was analyzed by Hierarchical clustering. RESULTS: CGH analysis showed average-12.9 gains and losses of chromosomes in LSCC. Relatively high frequencies of gains were found at 3q15-21 (14/18), 5p12-13 (11/18), 8q22-24 (6/18), 11q12-13 (8/18), 15q21-23 (7/18) and 18p11 (8/18), while those of losses at 1p13-21 (8/18), 3p21-23 (14/18), 5q21-22 (14/18), 9p12-pter (11/18) and 13q21-31 (8/18). Hierarchical clustering analysis showed that the differentially expressed genes were segregated into three groups. Three genes differentially expressed in process I (normal tissue to cancer) and process II (cancer to lymph node metastasis), and the Cy5/Cy3 ratios of twelve genes were either higher than 5.0 or lower than 0.2 in process I or process II. The fifteen special genes were first reported possibly to be the relationships with LSCC. In particular, 4 genes of them, which were cytochrome C oxidase Va, PPBP, EPHX2 and PON1, were first reported to correlate with tumorigenesis. SH3GL2, which was one of the 15 special genes, was located at one of the special chromosome regions, 9p12-pter. CONCLUSION: The important genes and special chromosomal aberrances might provide us a clue for further investigation of carcinogenesis, progression and metastasis in LSCC.

Asunto(s)

RESUMEN

OBJECTIVE: To explore the relationship between p53 gene mutations and STK15 abnormal expression in the development of human laryngeal squamous-cell carcinoma (LSCC). METHODS: LSCC tissues and matched normal tissues were taken during operation from 55 patients without previous chemotherapy or radiotherapy. Following polymerase chain reaction amplification direct sequencing single strand conformational polymorphism (PCR-SSCP) combined with silver staining were used to detect mutations of p53 gene in exons 7 and 8 (p53E7 and p53E8) using genomic DNA from 110 specimens including 55 LSCC tissues and 55 matched normal tissues. STK15 expression were evaluated by RT-PCR with beta-actin as internal control. RESULTS: The mutation rate of p53E7 was 30.9% (compared to normal tissues, chi(2) = 8.66, P < 0.01). There was no mutation in p53E8. In 38 of the 55 cases (69.1%), the STK15 mRNA expression level was higher than that of the paired normal tissue. The STK15 to beta-actin ratio of average density value was 1.22 +/- 0.49 in the cancer tissue, and 0.99 +/- 0.54 in the normal tissues (t = 4.539, P < 0.01). In 14 of the 17 cases (82.4%) with p53E7 mutations, the STK15 expression was higher than that of normal tissue. In the 38 cases with STK15 over-expression, p53E7 mutation was found in 14 cases (36.8%). The rate of concurrence of p53E gene mutations and STK15 over-expression (25.5%) was higher than that of only p53E gene mutations (chi(2) = 26.025, P < 0.01). CONCLUSION: There is significant association between p53 gene mutation and STK15 over-expression in laryngeal squamous-cell carcinoma.

Asunto(s)

RESUMEN

In order to find out the genes involved in the tumorigenesis of laryngeal carcinoma, we analyzed 18 laryngeal carcinoma with comparative genomic hybridization. Results show that each one has different degree of variances, included gains and losses of partial and whole chromosome. Each case has 12.9 abnormal regions averagely; losses are more than gains, equal to 7.2 and 5.7 per case respectively. Main regions are gains in chromosomes 3q (78%), 5p (61%), 11q (56%), 1q (50%), 8p (44%), 8q (39%) and 15q (39%), and losses of 3p (70%), 5q (78%), 9p (67%), 13q (50%), 1p (44%) and 14q (39%). There are many specific gains and losses in several chromosomes,especially the increase of copy number karyotype in 1p13-21(8/18), 3p21-23 (14/18), 5p21-22 (14/18), 9p12-pter (10/18) and 13q21-31 (8/18), while the decrease in 1q11-21 (11/18), 3q15-21 (12/18), 8p22-24 (6/18), 11q12-13 (8/18), 15q21-23 (7/18), 18p11 (8/18) are the characteristic varieties. These results suggest that there are oncogene, tumor suppressor gene and other associated genes involved in the tumorigenesis.

Asunto(s)

RESUMEN

Loss of tumor suppressor genes and apoptosis-associated genes was common event in laryngeal squamous cell carcinoma (LSCC). Apaf-1 (apoptotic protease activating factor-1) is a key factor in cytochrome C-dependent apoptotic pathway. To investigate the effect of Apaf-1 in progression of LSCC, we analyzed Apaf-1 from DNA and RNA levels. Semi-quantitative RT-PCR analysis of Apaf-1 mRNA showed that over 40 percent of LSCCs (11/27) were low expression compared to the para-neoplastic laryngeal tissues (PNTs). The results of CGH indicated loss in 2 of 18 cases but no amplification on chromosome 12q22-23. The LOH frequencies of D12S327, D12S1657, D12S393, D12S1706, D12S346 on 12q22-23 were 18.2%, 13.6%, 18.2%, 22.2% and 16.6%, respectively in 72 matched samples of LSCCs and PNTs. Methylation-specific PCR displayed that all of 11 LSCCs, whose expression of Apaf-1 mRNA down-regulated, were methylated in promoter regions. In contrast, only 1 of 16 LSCCs with no changes in Apaf-1 mRNA levels was methylated (chi2 test, P=0.0001). The results implied that abnormal expression of Apaf-1 participates in the genesis of LSCCs and decreased expression of Apaf-1 mRNA were not mainly due to the deletion of Apaf-1 gene. The Apaf-1 DNA methylation in promoter region might contribute to the decreased transcription of Apaf-1 in LSCCs.

Asunto(s)

RESUMEN

OBJECTIVE: To identify and characterize laryngeal cancer related novel genes located on chromosome 6q25. METHODS: Electric hybridization was performed in human genome database using EST (expression sequence tag) as probe. Novel genes were deduced by software from positive DNA clones and their cDNAs were amplified by RT-PCR using primers designed according to the sequence of the putative genes. RESULTS: A novel gene was cloned successfully. The full length of this gene was about 21 kb. It contained two exons and produced a 1006 bp transcript coding a protein with 235 amino acid residues. It's 5'flanking sequence contained two binding sites of oncoprotein c-Myc, thus it was named MTLC (c-Myc target from laryngeal cancer cells). Homologous assay showed that MTLC exhibited little overall homology to known human proteins but it exhibited good overall homology to mouse MT-MC1 protein with an identity of 78%. The primary structure of MTLC protein contained a nuclear location signal motif, but it did not have other conserved domains. The results of subcellular location experiment showed that MTLC expressed in nuclei of human hepatocellular carcinoma cell line Bel7402 cells, while a wide distribution of MTLC in various tissues was demonstrated by Northern blotting. CONCLUSION: MTLC may play an important role as a target gene of c-Myc and as a transcription factor in keeping the normal physiological process of cells.

Asunto(s)