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OBJECTIVE To counteract the arising problem of couple infertility, having good quality gametes is increasingly important. A molecule that seems to be useful to favor this condition is myo-inositol (MI), the most common stereoisomer of the inositol family, involved as second messenger in several cell pathways (osmoregulation, chromatin remodeling, gene expression, etc.). To evaluate this possibility, a treatment with myo-inositol in idiopathic infertile couples was performed in this randomized, placebo-controlled study. PATIENTS AND METHODS 86 couples were enrolled and randomly assigned to two groups, treated either with MI (Xyminal®, Lo.Li. Pharma Srl, Rome, Italy) or placebo suppositories, to evaluate the effects on sperm motility, cervical mucus quality and pregnancy rate. Moreover, in pregnancy cases, all routine controls on gestation progress and foetal health were performed to confirm the safety of this treatment. Metabolism inhibitor RESULTS As showed in this study, MI treatment allows an increase of total sperm motility (54.42 ± 8.72) in comparison to placebo group (46.21 ± 5.33). Moreover, MI mildly improves cervical mucus quality and increases the number of pregnancies (18.60%) in comparison to the placebo group (6.97%). CONCLUSIONS MI improves sperm motility and cervical mucus quality, increasing the probability of conception. The absence of adverse events both for the mother and the foetus confirmed the safety of this molecule in pregnancy, supporting even more its use for couples seeking pregnancy.OBJECTIVE In this premarket clinical study, we evaluated the efficacy and safety of a novel Hydrogel (HYADD4-G) for reducing low back pain (LBP) in patients with degenerative disc disease (DDD). PATIENTS AND METHODS Twenty-three patients with chronic LBP were enrolled. All patients presented with up to three lumbar black discs (Pfirrmann grade III or IV), LBP of at least 40 mm on the Visual Analogue Scale (VAS), and a Roland-Morris Disability Questionnaire (RMDQ) score of at least 9. Patients received a single 1.5 ml intradiscal injection of HYADD4-G (8 mg/ml), guided by X-ray. Our primary endpoint was the change in VAS score from baseline (day 0) to 4, 12, and 24 weeks. Our secondary endpoints were black disc hydration by Magnetic Resonance Imaging (MRI); the patient's therapeutic response according to the RMDQ; the quality of life, as determined by the EuroQol-5 Dimension (EQ-5D) Index; and a global assessment of patient health status, safety, and local tolerability. RESULTS Compared with baseline values, VAS score showed a significant reduction at each time point, and across the overall 24-week follow-up period (p less then 0.0001). MRI scanning observed a significant reduction in Pfirrmann grade from baseline, by at least one grade, at both week 4 (p = 0.0039) and week 24 (p = 0.0010). Furthermore, compared with baseline values, there was a significant reduction in RMDQ score at each timepoint, and across the entire study period (p less then 0.0001). The EQ-5D index increased significantly from baseline to week 24 (p = 0.0001). Finally, mean VAS scores for Patient Global Assessment (PTGA), and Clinical Observer Global Assessment (COGA), decreased significantly at each time point (p less then 0.0001), except for week 4. CONCLUSIONS HYADD4-G proved to be an efficient reliever of low back pain due to DDD.OBJECTIVE Previous studies have shown that nucleus pulposus (NP) cell death plays an extremely important role in the progress of intervertebral disc degeneration (IVDD). This research aimed to investigate the protective effect of the MLKL inhibitor necrosulfonamide (NSA) on human NP cells. PATIENTS AND METHODS We collected human NP tissues from the patients undergoing disc herniation operations and isolated NP cell from the samples. IL-1β (10 ng/ml) was used to establish a NP cells degenerated model. We analyzed the expression of caspase 3, caspase 8, RIPK1, RIPK 3, and MLKL in different degree of degenerate disc tissues. Cell viability was analyzed by the Cell Counting Kit-8 (CCK-8) assay. The expression levels of collagen Ⅱ, β-galactosidase (β-gal), caspase 3, caspase 8, RIPK1, RIPK 3, and MLKL, several inflammatory and anti-oxidant enzymes of different NP cell treat groups were detected by Western blotting, immunofluorescence staining, or RT-PCR. Flow cytometry was used to measure the ROS level and cell apoptosis. RESULTS The data showed that expression of caspase 3, caspase 8, RIPK1, RIPK 3, and MLKL markedly increased in severely degenerated disc tissues. IL-1β promoted the cell death of NP cells, while NSA could reverse the effects of IL-1β. We found that NAS increased the antioxidant SOD1, SOD2, CAT, and GPX3 expression and suppressed oxidative stress in the disc. Moreover, MMP3, MMP10, IL-6, and TNF-α were significantly suppressed by the NSA. CONCLUSIONS These results suggest that NSA prevented NP degradation via inhibiting apoptosis and necroptosis of NP cells. Besides, the protective function of antagonizing cell death may owe to the inflammation and oxidative stress suppression.OBJECTIVE The aim of this study was to explore the relationships between ADAMTS-13 gene polymorphisms and hypertension-induced atrial fibrillation (AF). PATIENTS AND METHODS A total of 200 hypertensive patients without AF (hypertension group) and 200 hypertensive patients with AF (AF group) treated in our hospital were enrolled. Then, peripheral blood was drawn from these subjects enrolled, and the genomic deoxyribonucleic acids (DNAs) were extracted for analysis of ADAMTS-13 gene polymorphism. Next, Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) was employed to determine the expression of ADAMTS-13 gene, and the correlations of ADAMTS-13 gene polymorphism with ADAMTS-13 gene expression and clinical indicators were analyzed. RESULTS Results revealed that there was a difference in the distribution of alleles of ADSMTS-13 rs3094374 (p=0.046) and rs34054981 (p=0.039) between AF group and hypertension group. The frequency of T allele of the locus rs3094374 and that of the locus rs34054981 MTS-13 gene was lower in patients carrying genotype TT in AF group. Furthermore, the ADAMTS-13 rs3094374 polymorphism was related to international normalized ratio (INR) (p=0.034), and the ADAMTS-13 rs28503257 polymorphism was correlated with the levels of brain natriuretic peptide (BNP) (p=0.047) and D-dimer (p=0.033). CONCLUSIONS ADAMTS-13 gene polymorphism is correlated with the susceptibility and procession of hypertension-induced AF.

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