Archives of Medical Research最新文献

Health problems associated with aging are a major public health concern for the future. Aging is a complex process with wide intervariability among individuals. Therefore, there is a need for innovative public health strategies that target factors associated with aging and the development of tools to assess the effectiveness of these strategies accurately. Novel approaches to measure biological age, such as epigenetic clocks, have become relevant. These clocks use non-sequential variable information from the genome and employ mathematical algorithms to estimate biological age based on DNA methylation levels. Therefore, in the present study, we comprehensively review the current status of the epigenetic clocks and their associations across the human phenome. We emphasize the potential utility of these tools in an epidemiological context, particularly in evaluating the impact of public health interventions focused on promoting healthy aging. Our review describes associations between epigenetic clocks and multiple traits across the life and health span. Additionally, we highlighted the evolution of studies beyond mere associations to establish causal mechanisms between epigenetic age and disease. We explored the application of epigenetic clocks to measure the efficacy of interventions focusing on rejuvenation.

Background

Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9).

Objective

To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers.

Methods

Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA).

Results

PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1.

Conclusions

After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

Background and objective

Disturbed autonomic nervous system (ANS) may promote inflammatory, immune, and oxidative stress responses, which may increase the risk of acute coronary events. S100β has been proposed as a biomarker of neuronal injury that would provide an insightful understanding of the crosstalk between the ANS, immune-inflammatory cells, and plaques that drive atherosclerosis. This study investigates the correlation between S100β, and functional coronary stenosis as determined by quantitative flow ratio (QFR).

Methods

Patients with unstable angina pectoris (UAP) scheduled for coronary angiography and QFR were retrospectively enrolled. Serum S100β levels were determined by enzyme-linked immunosorbent assay. The Gensini score was used to estimate the extent of atherosclerotic lesions and the cumulative sum of three-vessel QFR (3V-QFR) was calculated to estimate the total atherosclerotic burden.

Results

Two hundred thirty-three patients were included in this study. Receiver operator characteristic (ROC) curve indicated that S100β>33.28 pg/mL predicted functional ischemia in patients with UAP. Multivariate logistic analyses showed that a higher level of S100β was independently correlated with a functional ischemia-driven target vessel (QFR ≤0.8). This was also closely correlated with the severity of coronary lesions, as measured by the Gensini score (OR = 5.058, 95% CI: 2.912–8.793, p <0.001). According to 3V-QFR, S100β is inversely associated with total atherosclerosis burden (B = –0.002, p <0.001).

Conclusions

S100β was elevated in the functional ischemia stages of UAP. It was independently associated with coronary lesion severity as assessed by Gensini score and total atherosclerosis burden as estimated by 3V-QFR in patients with UAP.

Background

Ulipristal acetate (UPA) and levonorgestrel are used as emergency hormonal contraceptives. Although both are highly effective in preventing pregnancy, UPA shows efficacy even when taken up to 120 h after unprotected sexual intercourse.

Aims

To investigate whether the mechanism of UPA's contraceptive action involves post-fertilization effects.

Methods

In vitro and in vivo studies using cultured human endometrial cells and a pre-clinical rat model.

Results

Endometrial cells treated with UPA showed changes in the expression of receptivity gene markers and a significant decrease in trophoblast spheroids attached to the cultured cells. In addition, administration of UPA to female unmated rats decreased the expression of implantation-related genes in the endometrium and inhibited the number of implantation sites in the mated group compared to the non-treated group.

Conclusions

These results support that UPA as an emergency contraceptive might have post-fertilization effects that may affect embryo implantation.

Purpose

Sarcopenia or age-associated muscle loss is common in patients with Alzheimer's disease (AD). We have previously demonstrated the contribution of a leaky gut to sarcopenia in AD. Here, we asked whether resistant exercise (RE) reduces the sarcopenia phenotype by repairing intestinal leakage in patients with AD.

Method

A prospective, single-center study of older adults, including healthy controls and patients with AD (n = 44–51/group), was conducted to measure plasma zonulin and claudin-3 (markers of intestinal leakage), handgrip strength (HGS), and short physical performance battery (SPPB) as a measure of functional capacity. Measurements in patients with AD were performed at baseline and after 12 weeks of RE.

Results

At baseline, patients with AD had higher plasma zonulin and claudin-3 and lower HGS, gait speed, and SPPB scores than controls. RE reduced plasma zonulin and claudin-3 levels and improved HGS, SPPB scores, and gait speed. Regression analysis revealed robust relationships between changes in plasma zonulin and claudin-3 with HGS. Plasma zonulin was also positively associated with SPPB scores. In addition, RE downregulated plasma markers of inflammation and oxidative stress. However, the prevalence of sarcopenia based on low HGS and muscle atrophy or low SPPB was not affected by RE.

Conclusion

Taken together, disruption of the intestinal mucosal barrier may contribute to functional decline and sarcopenia in AD, which is incompletely recovered by RE. Circulating levels of zonulin and claudin-3 may be valuable in predicting sarcopenia and functional capacity in older adults with AD.

Aim

To evaluate the progress of the Mexican Institute of Social Security Recovery Policy (IMSS-RP) in addressing the decline in essential health services caused by the COVID-19 pandemic.

Methods

We analyzed eleven indicators of essential health services from 35 IMSS state delegations. The assessment included ambulatory and hospital care indicators such as breast and cervical cancer screening, family medicine, dental and specialty visits, diabetes and hypertension visits and health outcomes, deliveries, and elective surgeries. We analyzed the period before (January 2018–March 2021) and during (April 2021–June 2023) the implementation of the IMSS-RP. Statistical analysis to determine the association of the policy with service indicators and the change in their trends included an interrupted time series analysis and Poisson Generalized Estimating Equation models.

Results

The volume of services showed substantial declines during the first year of the COVID-19 pandemic, reaching between 11 and 81% of pre-pandemic levels. All services increased significantly during the first 27 months of the IMSS-RP implementation; specialty visits, cervical and breast cancer screening, and diabetes control exceeded pre-pandemic levels (103%,112%,103%, and 138%, respectively). However, only deliveries and the percentage of patients with controlled diabetes and hypertension showed a stable increase following the IMSS-RP implementation, whereas the remaining services showed an initial increase but began to decrease over time.

Conclusions

After 27 months of implementation, IMSS-RP achieved progress in increasing the volume of essential health services and improving chronic disease control. However, declining trends in several services signal the need to focalize the policy.

Background

Cognitive impairment is defined as a neurological condition that alters multiple cerebral functions such as reasoning, memory, concentration, and association, among others. It has found to be widely correlated with several factors such as oxidative stress. The latter could be induced by numerous pathological conditions characterized by increased levels of free radicals and decreased levels of antioxidants. Pregnancy is a period when women undergo a physiological state of oxidative stress due to hormonal changes and increased oxygen requirements to maintain pregnancy. However, when oxidative stress exceeds antioxidant capacity, this leads to cellular damage that promotes a diabetogenic state. Recent studies suggest a possible association between gestational diabetes and cognitive impairment, but the underlying mechanisms remain unclear.

Aims

We aim to explore the pathophysiological relationship between cognitive impairment and oxidative stress, focusing on the possible involvement of oxidative stress as the inducing mechanism.

Methods

We performed a comprehensive literature review through PubMed and Google Scholar. Our keywords were “neuroinflammation”, “cognitive impairment”, “gestational diabetes”, “oxidative stress”, “antioxidants”, and “free radicals”.

Results

From the initial 400 records identified, a total of 78 studies were analyzed and included in our study.

Conclusion

Oxidative stress plays a fundamental role in the development of cognitive impairment. Understanding this correlation is essential to the development of targeted medical interventions and, ultimately, promote research and prevention that will benefit the mother-child binomial in the short and long term.