Effect of add-on transcranial alternating current stimulation (tACS) in major depressive disorder: A randomized controlled trial.

BACKGROUND: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. OBJECTIVE: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. METHODS: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10-20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. RESULTS: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. CONCLUSION: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

Modulation of brain function and antidepressant effects by transcranial alternating current stimulation in patients with major depressive disorder: Evidence from ERP.

Transcranial alternating current stimulation (tACS) is an emerging non-invasive neuromodulation treatment for major depressive disorder (MDD), but its mechanism remains unclear. Therefore, we evaluated the effects of tACS on event-related potentials (ERP) based on a randomized controlled study. All patients were divided into two groups to receive either 20 sessions 77.5Hz-tACS or 20 sessions of sham stimulation during 4 weeks. The Hamilton Depression Rating Scale for Depression -17 item (HAMD-17) and ERP during face-word Stroop task were recorded before and after the treatment (the fourth weekend). Our findings indicate a significant alleviation of depressive symptoms after tACS. For the behavioral performance, sham group showed a significant decrease in reaction time to the sad incongruent condition and an increase in accuracy to the happy condition. The active group showed an increase in accuracy to the incongruent condition. ERP analysis revealed that tACS significantly shortened the latency of P2 to incongruent condition, decreased the amplitude and prolonged the latency of N2 to negative condition. These ERP alterations suggest a potential rectification of negative bias and enhancement of cognitive functioning in patients with MDD, offering insights into the antidepressant mechanisms of tACS.

In-Depth Understanding of the Oxidative Compatibility of Volatile Organic Compounds with Mn2O3 and Pt-Loaded Catalysts.

Designing suitable catalysts for efficiently degrading volatile organic compounds (VOCs) is a great challenge due to the distinct variety and nature of VOCs. Herein, the suitability of different typical VOCs (toluene and acetone) over Pt-based catalysts and Mn2O3 was investigated carefully. The activity of Mn2O3 was inferior to Pt-loaded catalysts in toluene oxidation but showed superior ability for destroying acetone, while Pt loading could boost the catalytic activity of Mn2O3 for both acetone and toluene. This suitability could be determined by the physicochemical properties of the catalysts and the structure of the VOC since toluene destruction activity is highly reliant on Pt0 in the metallic state and linearly correlated with the amount of surface reactive oxygen species (Oads), while the crucial factor that affects acetone oxidation is the mobility of lattice oxygen (Olat). The Pt/Mn2O3 catalyst shows highly active Pt-O-Mn interfacial sites, favoring the generation of Oads and promoting Mn-Olat mobility, leading to its excellent performance. Therefore, the design of abundant active sites is an effective means of developing highly adaptive catalysts for the oxidation of different VOCs.

Serum miR-497-5p serves as a diagnostic biomarker for acute coronary syndrome and predicts the occurrence of major adverse cardiovascular events after percutaneous coronary intervention.

This study aimed to investigate the diagnostic value of microRNA (miR)-497-5p in acute coronary syndrome (ACS) and its predictive value for the occurrence of adverse major adverse cardiovascular events (MACEs). Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of serum miR-497-5p in 110 ACS patients and 82 controls. And miR-497-5p levels were found to be significantly elevated in the patients (P < 0.001). Pearson correlation coefficient confirmed that miR-497-5p was positively correlated with Gensini scores (r = 0.684). The area under the Receiver-operating characteristic (ROC) curve was 0.861, which significantly identified patients with ACS, and was confirmed by logistic regression (OR = 8.533, 95%CI = 4.113-17.787, P < 0.001). Kaplan-Meier and Cox regression was performed to evaluate the predictive value of miR-497-5p in the occurrence of MACEs during a 6-month follow-up after percutaneous coronary intervention (PCI) in patients with ACS. The results demonstrated that miR-497-5p was an independent predictor of MACEs (HR = 4.773, 95%CI = 1.569-12.036, P = 0.013) and that patients with high level of miR-497-5p were more likely to develop MACEs after PCI (long-rank P = 0.019). Finally, miR-497-5p positively correlated with endothelial proinflammatory and adhesion factors. Our study suggests that serum miR-497-5p is a potential diagnostic marker for ACS and its elevated levels can predict a high risk of MACEs in ACS patients after PCI. And this may be associated with vascular endothelial injury.

Association of Cytochrome P450 2C9*3 and Angiotensin II Receptor 1 (1166A>C) Gene Polymorphisms With the Antihypertensive Effect of Irbesartan.

BACKGROUND: To analyze whether the cytochrome P450 enzyme 2C9*3 (CYP2C9*3) and angiotensin II receptor 1 (AGTR1) (1166A>C) gene polymorphisms are associated with the risk of essential hypertension (EH) and the antihypertensive effect of irbesartan. METHODS: A total of 2,057 EH patients and 286 healthy controls were enrolled for genotyping in which 598 EH patients were given irbesartan 150 mg/day for 4 weeks. Blood pressure of all subjects were determined before and at the end of 4-week treatment. RESULTS: There was no significant difference in genotype frequencies of CYP2C9*3 and AGTR1 (1166A>C) between EH and control groups. Subjects with *1*3/*3*3 genotypes of the CYP2C9*3 gene had larger systolic and diastolic blood pressure reductions (34.9 ± 15.5 vs. 29.3 ± 10.2 mm Hg and 22.8 ± 9.0 vs. 19.6 ± 8.5 mm Hg, respectively) compared with the *1*1 genotype. For AGTR1 (1166A>C) polymorphisms, although there was no significant difference among AC, CC, and AA genotypes, male subjects with AC/CC genotypes had larger systolic and diastolic blood pressure reductions (32.3 ± 1.3 vs. 29.3 ± 0.5 mm Hg and 21.6 ± 0.8 vs. 19.4 ± 0.1 mm Hg, respectively, P < 0.05) in response to irbesartan treatment compared with the AA genotype. CONCLUSIONS: Polymorphisms of CYP2C9*3 and AGTR1 (1166A>C) are not significantly different between EH and healthy controls. Male subjects with AC and CC genotypes of AGTR1 (1166A>C) show better antihypertensive effect of irbesartan than the AA genotype.

Increased serum bile acid level is associated with high-risk coronary artery plaques in an asymptomatic population detected by coronary computed tomography angiography.

BACKGROUND: There are limited data on the association between serum total bile acid level and coronary plaque characteristics. This study investigated the relationship between serum total bile acid level and the severity of coronary stenosis and coronary plaque features in an asymptomatic population using coronary computed tomography angiography (CTA). METHODS: A total of 1,137 consecutive participants with no known coronary artery disease (CAD) undergoing CTA as part of a general routine health evaluation were recruited. Serum total bile acid level and clinical parameters were assayed. Coronary stenosis and high-risk plaques features (napkin-ring sign, low-attenuation plaque, spotty calcification, positive remodelling) were evaluated. Associations between serum total bile acid concentration and high-risk coronary plaques was tested through univariate and multivariate analyses. RESULTS: A total of 101 high-risk coronary plaques subjects and 93 controls were eligible for study inclusion. The severity of coronary artery stenosis and high-risk coronary plaques increased with serum total bile acid level quartiles (all P<0.001). The independent predictor of high-risk coronary plaques in multivariate analysis was serum total bile acid level (P<0.001). Receiver operating characteristic (ROC) confirmed that serum total bile acid concentration significantly differentiated high-risk coronary plaques [the area under the curve (AUC) =0.876; P<0.001, with a sensitivity of 87.13% and a specificity of 86.02%]. CONCLUSIONS: Higher serum total bile acid level was associated with the severity of coronary artery stenosis and high-risk coronary artery plaques detected by CTA in asymptomatic populations.

Effect of siRNA-silencing of SALL2 gene on growth, migration and invasion of human ovarian carcinoma A2780 cells.

BACKGROUND: The role of Spalt-like gene-2 (SALL2) in tumorigenesis remains incompletely elucidated. This study investigated the effects of SALL2 on human ovarian carcinoma (OC) A2780 cells and the probable mechanism. METHODS: Expression of SALL2 in human OC cell lines were detected by reverse transcription PCR (RT-PCR) and Western blot analysis. A2780 cells were transfected with small-interfering ribonucleic acid (siRNA) to silence SALL2. SALL2 expression was detected by RT-PCR, Western blot analysis and immunofluorescence assay. Cell proliferation was measured by CCK-8 assay and flow cytometry (FCM). Apoptosis was measured by FCM. Cell migration was detected by real-time cell analysis. Cell invasion was detected by transwell assay. mRNA expression of p21 was detected by quantitative real-time PCR. Western blot analysis was used to determine the expression of matrix metalloproteinase (MMP)2, MMP9, protein kinase B (PKB, also called Akt), and phosphorylated-Akt (p-Akt). RESULTS: SALL2 was expressed in six OC cell lines, and the expression was the highest in A2780 cells. Compared with that in the Scramble group, SALL2 expression in A2780 was downregulated after transfection with siRNA-2 and siRNA-3 for 48 h. Compared with that in the Scramble group, proliferation of A2780 cells in the siRNA-2 group increased after transfection for 24, 48 and 72 h. In the siRNA-2 group, the proportion of A2780 cells decreased in the G0/G1 phase, and cell apoptosis decreased after transfection for 48 h. Compared with that in the Scramble group, the cell migration and invasion abilities of A2780 cells increased. Compared with that in the Scramble group, p21 mRNA expression in A2780 cells decreased after transfection with siRNA2. When SALL2 was silenced, the expression of MMP2/9 and p-Akt in A2780 cells increased. Furthermore, the PI3K inhibitor LY294002 could effectively reversed SALL2 siRNA-induced phosphorylation of Akt, migration and invasion of A2780 cells. CONCLUSION: Transient silencing of SALL2 promotes cell proliferation, migration, and invasion, and inhibits apoptosis of A2780 cells. In SALL2 siRNA-silenced cells, p21 expression was decreased. SALL2 knockdown by siRNA induces the migration and invasion of A2780 cells; this phenomenon is possibly associated with the increased expression of MMP2/9 and the activation of the PI3K/Akt signalling pathway.

Increased CCL19 expression is associated with progression in cervical cancer.

Cervical cancer is the third most common cancer and the fourth leading cause of malignancy related mortality in women worldwide. CCL19 is highly expressed in human cancer cells, and ligand CCL19 binding to CCR7 induces actin polymerization and pseudopodia formation. However, whether or not CCL19 is involved in EMT of human cervical cancer needs further investigation. Using quantitative PCR and western blot analyses, we found that CCL19 is overexpressed in cervical cancer cell lines and tissues. Knockdown of CCL19 via siRNA inhibited the proliferation of cervical cancer cells by increasing apoptosis. Further analyses showed that inhibitory effects of CCL19 on cell migration and invasion were partly associated with EMT process. In conclusion, these data indicate that CCL19 is abnormally expressed in cervical cancer, indicating a novel and important role for CCL19 in cervical cancer malignant transformation.

Clinical significance of leukocyte-associated immunoglobulin-like receptor-1 expression in human cervical cancer.

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is broadly expressed on the majority of immune cells; however, the biological role of LAIR in solid tumors has yet to be elucidated. In the present study, using immunohistochemical staining analysis, the expression of LAIR-1 in human cervical cancer (HCC) and nontumor-adjacent tissue specimens was determined, and the results indicated that the expression of LAIR-1 in HCC tissue was higher compared with that in noncancerous tissue. The χ2 test was used to analyze the correlation between the expression of LAIR-1 in tumor tissues with clinicopathological parameters. The results showed that the expression of LAIR-1 in the cancer cell nucleus was significantly associated with tumor size, pathological differentiation, T classification and clinical stage. In addition, the expression in the cytoplasm was evidently associated with the number of positive lymph nodes. The HCC cell line, ME-180, which does not express LAIR-1, was stably transfected using LAIR-1 cDNA. Cell Counting Kit-8 and an annexin V assay showed that the overexpression of LAIR-1 in ME-180 cells suppressed the proliferation and anti-apoptosis capacity of the cells. These findings demonstrated that LAIR-1 is markedly overexpressed in HCC tissue, and that its expression status is associated with tumor progression. LAIR-1 may be a biomarker and target in the diagnosis and treatment of patients with HCC.