RESUMO
Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.
Assuntos
Progressão da Doença , Cinesinas , Neoplasias da Próstata , Humanos , Cinesinas/metabolismo , Cinesinas/genética , Cinesinas/fisiologia , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , AnimaisRESUMO
Importance: Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant. Objective: To investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD. Design, Setting, and Participants: A single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis. Interventions: Patients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients. Main Outcomes and Measures: The primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42. Results: A total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], -1.17 [0.44]; 95% CI, -2.04 to -0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03). Conclusions and Relevance: These results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100054199.
Assuntos
Depressão Pós-Parto , Ketamina , Adulto , Feminino , Humanos , Gravidez , Adjuvantes Imunológicos , Cesárea , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/prevenção & controle , Ketamina/uso terapêutico , Adolescente , Adulto JovemRESUMO
BACKGROUND: BRD4 and PIN1 have been described to be involved in inflammation and vascular endothelial cell dysfunction, which in turn may increase pulse pressure. HYPOTHESIS: Genetic mutations within the BRD4 and PIN1 genes could affect the risk of high pulse pressure. METHODS: A total of four single nucleotide polymorphisms (SNPs) (BRD4: rs4808278; PIN1: rs2233678, rs2287838, and rs2233682) were genotyped in a cohort of 666 hypertensive patients and 232 normotensive controls with Chinese Han origin. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among the four SNPs within the BRD4 and PIN1 genes and diabetes. Logistic regression analysis was performed to calculate the odds ratio (ORs) (95% confidence interval (CI)) for the association between the four SNPs. RESULTS: Adjusted for age, weight, waist circumference, drinking, smoking, hypertension, and diabetes, high pulse pressure risk was significantly higher for carriers with the rs4808278-TT genotype in BRD4 than those with wild genotypes (OR: 0.400, 95% CI: 0.217-0.737, P* < 0.05). However, we did not find any significant association of rs2233678, rs2287838, and rs2233682 in PIN1 with high pulse pressure susceptibility after covariate adjustment. GMDR analysis indicated a significant three-locus model (P = 0.0107) involving rs4808278, rs2233678, and diabetes, the cross-validation consistency of the three-locus models was 9/10, and the testing accuracy was 57.47%. CONCLUSIONS: Genetic mutations within BRD4 (rs4808278) could affect the susceptibility to high pulse pressure in a southeastern Chinese population.