Weight changes from early to middle adulthood and cardiometabolic multimorbidity later in life among middle-aged and older adults: a retrospective cohort study from the NHANES 1999-2018.

Background: Weight gain in adulthood can influence the development of diabetes and cardiovascular diseases. It is speculated that weight gain is related to cardiometabolic multimorbility (CMM). This study was designed to examine the relationships between weight changes from early to middle adulthood and the risk of CMM. Methods: Data of the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycles were analyzed in the present study. Weights at age 25 years and 10 years before recruitment were self-reported and were used to define five weight change patterns including stable normal, maximum overweight, obesity to non-obesity, non-obesity to obesity, and stable obesity patterns. Meanwhile, absolute weight changes were classified into five groups: weight loss≥ 2.5 kg, weight change within 2.5 kg, 2.5 kg≤ weight gain < 10.0 kg, 10.0 kg≤ weight gain < 20.0 kg, and weight gain≥ 20.0 kg. CMM was defined as the coexistence of two or three of diabetes, coronary heart disease (CHD), and stroke. Results: A total of 25,994 participants were included. Across adulthood, compared to stable normal weight, maximal overweight, obesity to non-obesity, non-obesity to obesity, and stable obesity were consistently associated with increased risks of diabetes, CHD, and CMM. For instance, stable obesity was respectively related to 358.0% (HR: 4.58, 95% CI: 4.57, 4.58), 88.0% (HR: 1.88, 95% CI: 1.88, 1.88), and 292.0% (HR: 3.92, 95% CI: 3.91, 3.92) higher risks of diabetes, CHD, and CMM. Meanwhile, any account of weight loss and gain was linked to higher risks of diabetes, CHD, and CMM than weight change within 2.5 kg. However, participants with maximum overweight had a decreased incidence of stroke (HR: 0.85, 95% CI: 0.85, 0.86), and weight loss ≥ 2.5 kg and weight gain ≥ 2.5 and <20 kg were also related to a lower risk of stroke. J-shaped or U-shaped associations of absolute weight changes with the risks of diabetes, CHD, and CMM were observed. Conclusions: Maintaining a stable normal weight can benefit more from the prevention of diabetes, CHD, and CMM. Both weight gain and loss across adulthood were accompanied by increased risks of diabetes, CHD, and CMM.

Centrosomal Protein CEP135 Regulates the Migration and Angiogenesis of Endothelial Cells in a Microtubule-Dependent Manner.

BACKGROUND: Angiogenesis is the formation of blood vessels by sprouting from mature blood vessels and is regulated by multiple factors; however, the role of centrosome and centrosomal proteins (CEP) in angiogenesis needs further study. centrosomal protein 135 (CEP135) is an important centrosome-associated protein that can affect a variety of cellular processes, such as the cell cycle, but its effect on angiogenesis is still unknown. METHODS: Tube formation and in vivo angiogenesis assays were performed to confirm the effects of CEP135 on endothelial cell (EC) angiogenesis in vitro and in mice. Cell counting kit-8 (CCK-8), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry (FCM) and immunoblot assays were performed to confirm the effects of CEP135 on the proliferation and cell cycle of endothelial cells. Wound healing, transwell, and fluorescence staining were performed to confirm its effects on EC cell migration, polarization, and spindle orientation, and a tubulin turbidity assay was performed to confirm its effects on microtubule stabilization. RESULTS: We conducted a series of experiments to explore the potential role of CEP135 in angiogenesis. CEP135 siRNA obviously inhibits angiogenesis in vivo compared with the control. CEP135 could mediate cell proliferation and the cell cycle by mediating spindle orientation. Moreover, we showed that CEP135 is involved in the regulation of angiogenesis by affecting the migration of endothelial cells using wound closure and transwell assays. We further demonstrated that CEP135 promotes endothelial polarization and microtubule stability, thus affecting cell migration. CONCLUSIONS: CEP135 was involved in the polarization of centrosomes, which is important for the migration of human umbilical vein ECs (HUVECs). These findings indicated that CEP135 may promote the polarization of HUVECs and accelerate migration, which in turn promotes angiogenesis.

Specific Types of Physical Exercises, Dietary Preferences, and Obesity Patterns With the Incidence of Hypertension: A 26-years Cohort Study.

Objectives: To examine the associations of specific types of physical exercises, dietary preferences, and obesity patterns with incident hypertension. Methods: In this cohort study, obesity patterns were defined using general and abdominal obesity as G-/A-, G+/A- or G-/A+, and G+/A+. The type of physical exercises and dietary preferences were collected using a validated questionnaire. Participants with systemic blood pressure/diastolic blood pressure ≥140 mmHg/90 mmHg, use of antihypertensive medications, or a self-reported diagnosis were identified as hypertension. Results: There were 10,713 participants in this study. Martial arts, gymnastics, and ping pong could decrease the risk of hypertension (HR: 0.792, 0.884, and 0.855; and 95% CI: 0.743-0.845, 0.825-0.948, and 0.767-0.953, respectively). However, TV or computer usage, and consumption of fast food, soft/sugared drinks, and salty snack food could increase incident hypertension (HR: 1.418, 1.381, 1.233, and 1.225; and 95% CI: 1.315-1.529, 1.269-1.504, 1.157-1.314, and 1.139-1.316, respectively). Obese subjects had an increased risk of hypertension. Conclusion: The type of physical exercises, dietary preferences, and obesity patterns were associated with incident hypertension. More attention should be paid to these lifestyles to benefit health outcomes.

PPARα suppresses Th17 cell differentiation through IL-6/STAT3/RORγt pathway in experimental autoimmune myocarditis.

Family members of peroxisome proliferator-activated receptors (PPARs), such as PPARγ, have been shown to be effective in regulating T helper 17 (Th17) cell differentiation. However, whether PPARα, another important family member of PPARs, contributes to Th17 cell differentiation remains controversial. In the present study, we show that PPARα may be a negative regulator of Th17 cell differentiation. In CD4+ T cells from PPARα knockout mice, PPARα deficiency enhances IL-17 and IL-6 levels and promotes Th17 cell differentiation. In contrast, in CD4+ T cells from wild type mice, PPARα activation suppresses Th17 cell differentiation. Furthermore, IL-6 neutralizing antibody dose-dependently reduces the activity of STAT3 and down-regulates the protein expression of RORγt in CD4+ T cells from PPARα knockout mice but has no effect on that of wild type mice. On the other hand, in isolated CD4+ T cells from experimental autoimmune myocarditis (EAM) rats, PPARα agonist Fenofibrate decreased the expression of IL-17 and RORγt, increased the expression of Foxp3, while PPARα antagonist MK886 reversed these effects. Importantly, in vivo activation of PPARα ameliorates EAM by suppressing Th17 cell differentiation through reducing the expression of RORγt and phosphorylated STAT3 that are upregulated in EAM hearts. These results imply that PPARα suppresses Th17 cell differentiation through IL-6/STAT3/RORγt signaling pathway and suggest that PPARα may become a molecular target for treating autoimmune myocarditis.

Propofol sedation versus no sedation in detection of pharyngeal and upper gastrointestinal superficial squamous cell carcinoma using endoscopic narrow band imaging: a multicenter prospective trial.

Intravenous propofol can provide a superior quality of sedation compared to standard sedation for upper gastrointestinal endoscopy. However, the utility of propofol sedation for the endoscopic early detection of superficial pharyngeal and esophageal squamous cell carcinoma has not been investigated. In a multicenter, prospective trial, 255 patients with esophageal squamous cell carcinomas (ESCCs) were assigned to receive propofol sedation or no sedation according to their own willingness. The primary aim was to compare the detection rates of superficial cancer in the pharyngeal region and the esophagus between two groups. The secondary aim was to evaluate factors associated with technical adequacy. The detection rate was higher in the propofol sedation vs. no sedation group for H&N region (6.06% vs. 2.40%), but not significantly (P=0.22). However, the small lesion (less than 10 mm in diameter) detection rate was higher in sedation vs. no sedation group for H&N region (88.89% vs. 33.33%; P=0.048). The median time for pharyngeal observation in the sedation group was faster than in the no sedation group (20.6 s vs. 44.3 s; P<0.001). Ninety-five percent of H&N region evaluations were totally complete in sedation compared with sixty percent in the no sedation group (P<0.001). The overall p value indicated that only smoking habit was associated with incomplete pharyngeal observation (P<0.05), and it was more difficult to accomplish a complete pharyngeal observation in patients who smoked more than 10 packs per day. Intravenous propofol sedation compared to no intravenous sedation during conventional upper gastrointestinal endoscopy can facilitate a more complete pharyngeal examination and increase the detection rate of superficial H&N squamous cell carcinoma in high risk patients.