Sex differences in the relationship between depression and Alzheimer's disease-mechanisms, genetics, and therapeutic opportunities.

Depression and Alzheimer's disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression-AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients' distinct needs.

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

[Panax notoginseng saponins improve monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting ADAM10/Notch3 signaling pathway].

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.

How does HbA1c predict mortality and readmission in patients with heart failure? A protocol for systematic review and meta-analysis.

BACKGROUND: Accumulating evidence suggests that HbA1c levels, a common clinical indicator of chronic glucose metabolism over the preceding 2-3 months, are independent risk factors for cardiovascular disease, including heart failure. However, conflicting evidence obscures clear cutoffs of HbA1c levels in various heart failure populations. The aim of this review is to assess the possible predictive value and optimal range of HbA1c on mortality and readmission in patients with heart failure. METHODS: A systematic and comprehensive search will be performed using PubMed, Embase, CINAHL, Scopus, and the Cochrane Library databases before December 2022 to identify relevant studies. All-cause mortality is the prespecified primary endpoint. Cardiovascular death and heart failure readmission are secondary endpoints of interest. We will only include prospective and retrospective cohort studies and place no restrictions on the language, race, region, or publication period. The ROBINS-I tool will be used to assess the quality of each included research. If there were sufficient studies, we will conduct a meta-analysis with pooled relative risks and corresponding 95% confidence intervals to evaluate the possible predictive value of HbA1c for mortality and readmission. Otherwise, we will undertake a narrative synthesis. Heterogeneity and publication bias will be assessed. If heterogeneity was significant among included studies, a sensitivity analysis or subgroup analysis will be used to explore the source of heterogeneity, such as diverse types of heart failure or patients with diabetes and non-diabetes. Additionally, we will conduct meta-regression to examine the time-effect and treatment-effect modifiers on all-cause mortality compared between different quantile of HbA1c levels. Finally, a restricted cubic spline model may be used to explore the dose-response relationship between HbA1c and adverse outcomes. DISCUSSION: This planned analysis is anticipated to identify the predictive value of HbA1c for mortality and readmission in patients with heart failure. Improved understanding of different HbA1c levels and their specific effect on diverse types of heart failure or patients with diabetes and non-diabetes is expected to be figured out. Importantly, a dose-response relationship or optimal range of HbA1c will be determined to instruct clinicians and patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration details: CRD42021276067.

Systemic inflammation markers and the prevalence of hypertension: A NHANES cross-sectional study.

Systemic inflammation markers have been highlighted recently as related to cardiac and non-cardiac disorders. However, few studies have estimated pre-diagnostic associations between these markers and hypertension. In the National Health and Nutritional Examination Survey from 1999 to 2010, 22,290 adult participants were included for analysis. We assessed associations between four systemic inflammation markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and hypertension prevalence in multivariate logistic regression analysis with odds ratio (OR) and 95% confidence interval (CI). To further explore their associations, subgroup and sensitivity analyses were performed. In continuous analyses, the ORs for hypertension prevalence per ln-transformed increment in SII and NLR were estimated at 1.115 and 1.087 (95% CI: 1.045-1.188; 1.008-1.173; respectively). Compared to those in the lowest tertiles, the hypertension risks for subjects in the highest SII and NLR tertiles were 1.20 and 1.11 times, respectively. Conversely, we found that PLR and LMR were negatively associated with hypertension prevalence in continuous analyses (1.060, 0.972-1.157; 0.926, 0.845-1.014; respectively), and the highest PLR and LMR tertiles (1.041, 0.959-1.129; 0.943, 0.866-1.028; respectively). Also, subgroup and sensitivity analyses indicated that SII had a greater correlation to hypertension. In conclusion, we find positive associations between SII and NLR and the prevalence of hypertension in this cross-sectional study. Our findings highlight that SII may be a superior systemic inflammation warning marker for hypertension.

U-Shaped Relationship of Non-HDL Cholesterol With All-Cause and Cardiovascular Mortality in Men Without Statin Therapy.

Background: Non-HDL-C is well established causal risk factor for the progression of atherosclerotic cardiovascular disease. However, there remains a controversial pattern of how non-HDL-C relates to all-cause and cardiovascular mortality, and the concentration of non-HDL-C where the risk of mortality is lowest is not defined. Methods: A population-based cohort study using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Male participants without statin therapy were divided into the six groups according to non-HDL-C levels (<100, 100-129, 130-159, 160-189, 190-219, ≥220 mg/dl). Multivariable Cox proportional hazards models were conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the relationship between non-HDL-C and mortality, Kaplan-Meier survival curves, restricted cubic spline curves, and subgroup analysis were performed. Results: Among 12,574 individuals (average age 44.29 ± 16.37 years), 1,174(9.34%) deaths during a median follow-up 98.38 months. Both low and high non-HDL-C levels were significantly associated with increased risk of all-cause and cardiovascular mortality, indicating a U-shaped association. Threshold values were detected at 144 mg/dl for all-cause mortality and 142 mg/dl for cardiovascular mortality. Below the threshold, per 30 mg/dl increase in non-HDL-C reduced a 28 and 40% increased risk of all-cause (p < 0.0001) and cardiovascular mortality (p = 0.0037), respectively. Inversely, above the threshold, per 30 mg/dl increase in non-HDL-C accelerated risk of both all-cause mortality (HR 1.11, 95% CI 1.03-1.20, p = 0.0057) and cardiovascular mortality (HR 1.30, 95% CI 1.09-1.54, p = 0.0028). Conclusions: Non-HDL-C was U-shaped related to all-cause and cardiovascular mortality among men without statin therapy.

Associations Between Serum Soluble α-Klotho and the Prevalence of Specific Cardiovascular Disease.

Objective: Accumulating experimental evidence has identified the beneficial effects of the anti-aging protein, serum soluble α-Klotho, on longevity, and the cardiovascular system. Although a previous study has revealed the predictive value of α-Klotho on total cardiovascular disease (CVD), the associations between α-Klotho and specific CVDs, including congestive heart failure (CHF), coronary heart disease (CHD), myocardial infarction (MI), and stroke, remains to be fully elucidated in humans. Methods: For 8,615 adults in the 2007 to 2016 National Health and Nutrition Examination Survey, stratified multivariable logistic regression models, restricted cubic spline curves, and subgroup analyses were used to evaluate the associations between α-Klotho and the four specific CVDs. Results: In the quartile analyses, compared to those in the highest quartile, participants in the lowest level of α-Klotho were significantly associated with CHF [odds ratio (OR) = 1.46, 95% CI: 1.09-1.97] and MI (1.33, 1.02-1.74), which was not the case for CHD (1.12, 0.91-1.38) or stroke (0.96, 0.73-1.25). Each unit increment in the ln-transformed α-Klotho concentrations was only positively associated with a 38 and 24% reduction in the prevalence of CHF and MI, respectively. Restricted cubic spline curves indicated that the α-Klotho was correlated with CHF and MI in linear-inverse relationships. Conclusion: The present findings suggested that the serum soluble α-Klotho is significantly associated with the prevalence of CHF and MI. To better determine whether α-Klotho is a specific biomarker of CVD, particularly for CHD and stroke, further research in humans is needed.

Analysis of the Dose-Response Effects of Physical Activity on Cardiocerebrovascular and All-Cause Mortality in Hypertension.

Background: Leisure-time moderate-to-vigorous physical activity (MV-PA) has been consistently regarded as a protective factor to prevent and treat hypertension. However, the effect of different levels of MV-PA against cardiocerebrovascular and all-cause mortality in hypertension is still unclear. The aim of this study was to explore the dose relationships of MV-PA on these adverse outcomes in hypertension. Methods: In the National Health and Nutritional Examination Survey (NHANES) from 1999 to 2006, participants with hypertension were enrolled and classified into inactive (0 MET-h/week), low-active (0 < to < 7.5 MET-h/week), and high-active (≥ 7.5 MET-h/week) groups. A multivariate Cox regression analysis was conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the association between different levels of MV-PA and adverse outcomes, Kaplan-Meier survival curves, subgroup analysis, and restricted cubic spline curves were performed. Results: During a median 10.93-year follow-up, 1,510 and 347 patients had died from any causes and cardiocerebrovascular, respectively. The high-active group had the highest event-free survivals of all outcomes compared with low-active and inactive groups. A multivariate Cox regression analysis demonstrated that the high-active and low-active groups were associated with reduced risks of all-cause [HR: 0.70, 95% CI: 0.60-0.82; 0.76 (0.68-0.86), respectively] and cardiocerebrovascular mortality [0.56 (0.41-0.77); 0.63 (0.50-0.81), respectively] compared with the inactive group. Subgroup analysis and restricted cubic spline curves showed that MV-PA surpassing 15 MET-h/week could decrease the risks of cardiovascular and all-cause mortality with inverse relationships, which was not the case for cerebrovascular mortality, indicating a U-shaped association. Conclusion: Our study suggests that highly active MV-PA of 7.5 to < 15 MET-h/week was associated with the lowest risks of cardiocerebrovascular and all-cause mortality in hypertension.

Correlation between Characteristics of Coronary Plaque and Chinese Medicine Syndromes of Coronary Heart Disease: A Cross-Sectional Study Analysed by Intravascular Ultrasound.

OBJECTIVE: To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS). METHODS: Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS). RESULTS: A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01). CONCLUSIONS: Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.

Effect of lanthanum carbonate on the progression of coronary artery calcification in hemodialysis patients: A meta-analysis of randomized controlled trials.

INTRODUCTION: Coronary artery calcification and cardiac abnormalities are common in hemodialysis patients. The value of lanthanum carbonate over calcium-based phosphate binders in managing the progression of coronary artery calcification is debated. We reviewed all randomized controlled trials (RCTs) comparing the two strategies in these patients. METHODS: RCTs comparing lanthanum carbonate with calcium-based phosphate binders used in adult hemodialysis patients were identified in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang databases. FINDINGS: Ten RCTs involving 687 patients were suitable for inclusion. Compared with calcium-based phosphate binders, lanthanum carbonate yielded lower coronary artery calcium scores (weighted mean difference, WMD: -74.28, 95% CI: -149.89, 1.33), change in coronary artery calcium scores (WMD: -105.18, 95% CI: -113.83, -96.53), and left ventricular mass index (WMD: -29.95, 95% CI: -54.25, -7.45). Lanthanum carbonate was significantly associated with lower levels of serum phosphate (WMD: -0.18, 95% CI: -0.26, -0.10), calcium (WMD: -0.22, 95% CI: -0.25, -0.20), and fibroblast growth factor 23 (FGF23) (standard mean difference: -3.78, 95% CI: -5.60, -1.96) but not intact parathyroid hormone (WMD: -4.23, 95% CI: -64.12, 55.65). Moreover, a reduced risk of nonfatal cardiovascular events (OR: 0.31, 95% CI: 0.10-0.97) but not all-cause mortality (OR: 1.08, 95% CI: 0.39-3.01) in lanthanum carbonate therapy was observed. DISCUSSION: In hemodialysis patients, lanthanum carbonate therapy may impede the progression of coronary artery calcification and left ventricular mass index and lead to reduced serum phosphate, calcium, FGF23, and nonfatal cardiovascular events compared with calcium-based phosphate binders. However, more well-designed RCTs are required for confirmation.

Long non-coding RNA RP11-81H3.2 suppresses apoptosis by targeting microRNA-1539/COL2A1 in human nucleus pulposus cells.

Intervertebral disk degeneration (IDD) is a severe health problem that results in lower back pain and disability. Previous evidence has indicated that excessive apoptosis of nucleus pulposus (NP) cell is involved in the occurrence and development of IDD. However, the underlying mechanisms regulating NP cell apoptosis are unclear. The present study aimed to investigate the function of a novel long non-coding RNA RP11-81H3.2 in modulating NP cell apoptosis and the potential underlying mechanisms. The results demonstrated that the RP11-81H3.2 expression levels were significantly decreased in NP tissues from patients with IDD compared with those from healthy controls, and that lower expression levels were associated with higher-grade disk degeneration. Functionally, RP11-81H3.2 silencing promoted apoptosis and decreased the viability of NP cells derived from tissue samples of patients with IDD, whereas RP11-81H3.2 overexpression induced opposite effects. Bioinformatics analysis, luciferase assays and reverse transcription-quantitative PCR revealed that microRNA (miR)-1539 was a direct target of RP11-81H3.2. A mechanistic analysis demonstrated that RP11-81H3.2 functioned as an RNA sink to downregulate miR-1539, which led to the upregulation of collagen type 2 α 1 chain (COL2A1), a target of miR-1539. Collectively, the present results suggested that lower RP11-81H3.2 expression levels were associated with higher-grade IDD, and that RP11-81H3.2 inhibited NP cell apoptosis by decreasing the levels of miR-1539 to increase COL2A1 expression levels. The present study identified a beneficial role of RP11-81H3.2 against NP cell apoptosis.

Nitrates and risk of vasovagal reaction in femoral sheath removal after percutaneous intervention : A retrospective observational study.

BACKGROUND: The aim of this study was to analyze the risk factors for vasovagal reaction (VVR) in manual femoral sheath removal after percutaneous coronary intervention and to discuss methods for the prevention and control of VVR. METHODS: The data of 455 patients who underwent percutaneous intervention in four interventional centers during a period of 30 months were retrospectively analyzed. Patients were divided into a VVR group and a control group according to whether VVR developed. The clinical data of all patients were analyzed using univariate and multivariate logistic regression analysis to examine VVR -related factors. RESULTS: A total of 455 patients underwent 464 manual femoral sheath removal operations, of whom 12 developed VVR (2.59%). Of these 12 VVR patients, one had VVR during and 11 had VVR after the intervention. There were no statistically significant differences between the two groups in age, body mass index, gender, time of sheath removal, proportions of patients with hypertension, diabetes, and hyperlipemia, laboratory values of hemoglobin a1c, and ejection fraction (p > 0.05). Compared with the control group, use of nitrates was the only risk factor with a significant correlation with VVR (p = 0.012). CONCLUSION: In manual femoral sheath removal, the use of nitrates is the most important risk factor for the occurrence of VVR after percutaneous intervention.

Syntheses, characterization and biological activities of rare earth metal complexes with curcumin and 1,10-phenanthroline-5,6-dione.

Three new solid complexes have been synthesized by the reaction of rare earth(III) nitrate with the first ligand curcumin (HL) and the second ligand 1,10-phenanthroline-5,6-dione (L') in alcohol solution (pH=6.5-7.0). The composition of the complexes has been characterized by elemental analysis, molar conductivity, thermogravimetric analysis, IR, UV-vis methods. The results reveal that beta-diketone group of the first ligand to coordinates with rare earth ions in bidentate mode after deprotonated. But the second ligand uses its two N atoms coordinates with rare earth ions in bidentate mode. The general formula of the complexes is REL(3)L' (RE=Sm, Eu, Dy). The results of antibacterial activity indicated that the complexes have excellent antibacterial ability for the testing bacterium than that of curcumin. The result of agarose gel electrophoresis suggested that the complex of SmL(3)L' can cleave the plasmid DNA at physiological pH and temperature. And it was found that the cleavage process of plasmid DNA was sensitive to pH, however, adding radical scavengers almost had no effect on the DNA cleavage reaction, therefore, the cleavage of DNA by SmL(3)L' does not produce diffusible hydroxyl radicals via the Fenton reaction.