Maternal BMI changes from the prepregnancy to postpartum period are associated with postpartum cardiometabolic risk factors: a longitudinal study.

PURPOSE: This study aimed at investigating the associations between the total body mass index (BMI) change at 3 or 4 years postpartum compared to the prepregnancy and cardiometabolic risk factors. METHODS: This longitudinal study included 1305 participants. Based on the total postpartum BMI changes, they were divided into < 0 units, 0-1.7 units, and > 1.7 units groups using the interquartile range. Multiple linear regression models were used to analyze the associations. RESULTS: Compared to the reference group, there was a progressive increase in the ßcoefficient (ßcoef) of homeostasis model assessment of insulin resistance (HOMA-IR) of cardiometabolic risk in the following groups: the '0-1.7 units' group with the 'overweight traj' [ßcoef 0.33; 95% confidence intervals (CI) 0.22, 0.44)] or the 'obesity traj' [0.66; (0.45, 0.88)] and the '> 1.7 units' group with the 'normal traj' [0.33; (0.22, 0.44)], the 'overweight traj' [0.54; (0.41, 0.67)] or the 'obesity traj' [0.97; (0.79, 1.15)]. The same increasing trend of ßcoef was also found in DBP, FPG, LDL, WHR, BF%. However, the '< 0 units' group with the 'low traj' [0.13; (0.06, 0.21)] and the '0-1.7 units' group with the 'low traj' [0.08; (0.03, 0.13)] had higher high-density lipoprotein cholesterol (HDL-C) level than the reference group. CONCLUSION: Women with a postpartum BMI gain > 1.7 units are positively associated with cardiometabolic risk factors, especially for those in the 'obesity traj' or 'traj D'. Conversely, women with a postpartum BMI loss > 0 units have negative association with cardiometabolic risk factors, especially for those in the 'low traj' or 'traj B'.

Mediation effect of maternal triglyceride and fasting glucose level on the relationship between maternal overweight/ obesity and fetal growth: a prospective cohort study.

BACKGROUND: Previous studies have suggested that maternal overweight/obesity is asscociated with macrosomia. The present study aimed to investigate the mediation effects of fasting plasma glucose (FPG) and maternal triglyceride (mTG) in the relationship between maternal overweight/obesity and large for gestational age (LGA) among non-diabetes pregnant women. METHODS: This prospective cohort study was conducted in Shenzhen from 2017 to 2021. A total of 19,104 singleton term non-diabetic pregnancies were enrolled form a birth cohort study. FPG and mTG were measured at 24-28 weeks. We analyzed the association of maternal prepregancy overweight/obesity with LGA and mediation effects of FPG and mTG. Multivariable logistic regression analysis and serial multiple mediation analysis were performed. The odds ratio (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: Mothers who were overweight or obese had higher odds of giving birth to LGA after adjusting potential confounders (OR:1.88, 95%CI: 1.60-2.21; OR:2.72, 95%CI: 1.93-3.84, respectively). The serial multiple mediation analysis found prepregnancy overweight can not only have a direct positive effect on LGA (effect = 0.043, 95% CI: 0.028-0.058), but also have an indirect effect on the LGA through two paths: the independent mediating role of FPG (effect = 0.004, 95% CI: 0.002-0.005); the independent mediating role of mTG (effect = 0.003,95% CI: 0.002-0.005). The chain mediating role of FPG and mTG has no indirect effect. The estimated proportions mediated by FPG and mTG were 7.8% and 5.9%. Besides, the prepregnancy obesity also has a direct effect on LGA (effect = 0.076; 95%CI: 0.037-0.118) and an indirect effect on LGA through three paths: the independent mediating role of FPG (effect = 0.006; 95%CI: 0.004-0.009); the independent mediating role of mTG (effect = 0.006; 95%CI: 0.003-0.008), and the chain mediating role of FPG and mTG (effect = 0.001; 95%CI: 0.000-0.001). The estimated proportions were 6.7%, 6.7%, and 1.1%, respectively. CONCLUSION: This study found that in nondiabetic women, maternal overweight/obesity was associated with the occurence of LGA, and this positive association was partly mediated by FPG and mTG, suggesting that FPG and mTG in overweight/obese nondiabetic mothers deserve the attention of clinicians.

Third-Trimester Maternal Serum Chemerin and Hypertension After Preeclampsia: A Prospective Cohort Study.

Background Limited data are available for postpartum hypertension prediction after preeclampsia. Methods and Results We examined the association between maternal serum chemerin levels in patients with preeclampsia and blood pressure (BP) levels after delivery in a prospective birth cohort of 15 041 singleton pregnant women. A total of 310 cases among 322 patients with preeclampsia (follow-up rate, 96.3%) were followed up during a mean 2.8 years after delivery. Compared with matched uncomplicated controls (n=310), serum chemerin measured at ≈35 gestational weeks was significantly increased in preeclampsia (171.8±49.2 versus 140.2±53.5 ng/mL; P<0.01) and positively correlated with the occurrence of postpartum hypertension, defined as either BP ≥130/80 mm Hg (per 1-SD increase: odds ratio [OR], 4.01 [95% CI, 2.77-5.81]) or as BP ≥140/90 mm Hg (per 1-SD increase: OR, 1.70 [95% CI, 1.28-2.25]) in patients with preeclampsia. The addition of chemerin levels improved the predictive performance of the clinical variable-derived prediction models for postpartum hypertension (for BP ≥130/80 mm Hg: area under the curve, 0.903 [95% CI, 0.869-0.937], Δ area under the curve, 0.070, P<0.001; for BP ≥140/90 mm Hg: area under the curve, 0.852 [95% CI, 0.803-0.902], Δ area under the curve, 0.030, P=0.002). The decision curve analysis revealed a net benefit of the chemerin-based prediction model for postpartum BP ≥130/80 mm Hg. Conclusions This study provides the first evidence supporting the independent predictive role of third-trimester maternal chemerin levels for postpartum hypertension after preeclampsia. Future study is warranted for external validation of this finding.

MSCs ameliorate hepatocellular apoptosis mediated by PINK1-dependent mitophagy in liver ischemia/reperfusion injury through AMPKα activation.

Hepatocyte apoptosis is the main pathophysiological process underlying liver ischemia/reperfusion (I/R) injury. Mitochondrial abnormalities have a vital role in hepatocellular damage. The hepatoprotective effects of mesenchymal stem cells (MSCs) have been previously demonstrated. In this study, we aim to investigate the effect and potential mechanism of MSCs against liver I/R injury. Effects of MSCs were studied in mice liver I/R injury model and in a hypoxia/reoxygenation (H/R) model of L02 hepatocytes. The potential mechanisms of MSCs on these in vivo and in vitro I/R-induced hepatocellular apoptosis models were studies. Accompanied by the improvement of hepatic damage, MSCs exhibited capabilities of controlling mitochondrial quality, shown by reduced mitochondrial reactive oxygen species (mtROS) overproduction, decreased the accumulation of mitochondrial fragmentation, restored ATP generation and upregulated mitophagy. Furthermore, we descripted a potential mechanism of MSCs on upregulating mitophagy and found that the reduced Parkin and PINK1 expression and inactivated AMPKα pathway were observed in the liver tissue in I/R model. These effects were reversed by MSCs treatment. In vitro study showed that MSC-conditioned medium (MSC-CM) suppressed hepatocellular apoptosis and inhibited mtROS accumulation in the H/R environment. And these effects of MSC-CM were partially blocked after the cells were transfected with PINK1 siRNA or added with dorsomorphin. Collectively, our findings provide a novel pharmacological mechanism that MSCs exert hepatoprotective effect in liver I/R injury via upregulating PINK1-dependent mitophagy. In addition, this effect might be attributed to the modulation of AMPKα activation.

Endothelial progenitor cells promote viability and nerve regenerative ability of mesenchymal stem cells through PDGF-BB/PDGFR-ß signaling.

Denervation-induced erectile dysfunction (ED) is a prevailing health problem. Our previous study revealed that endothelial progenitor cells (EPCs) promoted the effect of mesenchymal stem cells (MSCs) on restoration of denervation-induced ED in rats. However, underling mechanisms are still largely elusive. In this study, EPCs and MSCs were co-cultured and resorted to co-EPCs and co-MSCs. EPCs-derived paracrine factors containing PDGF-BB (platelet-derived growth factor) were detected, and MSCs were pre-treated with PDGF-BB, while co-MSCs were pre-treated with PDGFR inhibitor AG1296. Either viability or nerve regenerative ability of MSCs was evaluated. In addition, inhibition of either PI3K/Akt or MEK/Erk pathway was performed to evaluate the role of PI3K/Akt and MEK/Erk pathway in PDGF-BB-induced viability of MSCs. The results revealed that PDGF-BB significantly increased the proportion of PDGFR-ß+ MSCs, and promoted both in-vitro and in-vivo viability, as well as nerve regenerative capacity and erectile function restoration of MSCs in rats. Inhibition of PI3K/Akt, MEK/Erk pathway or mTOR led to decrease of PDGF-BB/PDGFR-ß induced viability of MSCs. To our knowledge, our study first demonstrates that EPCs promote viability and potential nerve regenerative ability of MSCs through PDGF-BB/PDGFR-ß signaling and its downstream PI3K/Akt and MEK/Erk pathways. mTOR acts as a co-mediator in PI3K/Akt and MEK/Erk pathways.

Surgery vs conservative treatment for type II and III odontoid fractures in a geriatric population: A meta-analysis.

BACKGROUND: It is unclear whether surgery or conservative treatment is more suitable for elderly patients with type II and type III odontoid fractures. We performed this meta-analysis to compare the efficacy of surgical and conservative treatments for type II and type III odontoid fractures. METHODS: A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library in January 2017. Only articles comparing surgery with conservative treatment in elderly patients with type II and type III odontoid fractures were selected. After 2 authors independently assessed the retrieved studies, 18 articles were included in this meta-analysis, and the primary endpoints were the nonunion rate and mortality rate. The secondary outcomes were patient satisfaction, complications, and the length of the hospital stay. The quality of the included studies was evaluated using the modified Newcastle-Ottawa scale. Sensitivity analyses were performed for high-quality studies, and the publication bias was evaluated using a funnel plot. RESULTS: Lower nonunion (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.18-0.40, P < .05) and mortality rates (OR: 0.52, 95% CI: 0.34-0.79, P < .05) confirmed the superiority of surgery in treating type II and type III fractures. The secondary outcomes differed. Patients in the surgery group felt more satisfied with the outcome (OR: 3.44, 95% CI: 1.19-9.95, P < .05), and the complications were similar in the 2 groups (OR: 1.14, 95% CI: 0.78-1.68, P = .5), whereas patients in conservative groups spent less time in the hospital (OR: 5.10, 95% CI: 2.73-7.47, P < .05). The results of the subgroup analyses and sensitivity analysis were similar to the original outcomes, and no obvious publication bias was observed in the funnel plot. CONCLUSION: Most elderly (younger than 70 years) patients with type II or type III odontoid fractures should be considered candidates for surgical treatment, due to the higher union rate and lower mortality rate, while statistically significant differences were not observed in the population with an advanced age (older than 70 years). Therefore, the selection of the therapeutic approach for elderly patients with odontoid fractures requires further exploration. Simultaneously, based on our meta-analysis, a posterior arthrodesis treatment was significantly superior to the anterior odontoid screw treatment.

Transplantation of induced pluripotent stem cell-derived mesenchymal stem cells improved erectile dysfunction induced by cavernous nerve injury.

Erectile dysfunction (ED) is an important kind of postoperative complication of pelvic surgery that affects patients' quality of life. Transplantation of mesenchymal stem cells (MSC) has been found to alleviate ED caused by cavernous nerve injury (CNI) in rats. However, little is known about whether induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) have a therapeutic effect on CNI ED. We established an ED model on rats and evaluated the effect of iMSC on it. Methods: Eight-week-old male Sprague-Dawley rats were assigned to four groups and received following operation: sham operation (sham group); bilateral CNI and phosphate-buffered saline (PBS) injections (PBS group); bilateral CNI and adipose-derived mesenchymal stem cells transplantation (adMSC group); or bilateral CNI and iMSC injection (iMSC group). After therapy, the cavernous nerve was stimulated by electricity and the intracavernous pressure (IAP)/mean arterial blood pressure (MAP) was measured. The endothelial and smooth muscle tissue in the penis was assessed histologically with Masson's trichrome stain. Immunofluorescence/immunohistochemical stains were applied for the detection of nNOS, vWF, eNOS, SMA, Desmin, S100ß, and caspase-3. Nude rats CNI ED model was established for the evaluation of iMSC longevity and differentiation capacity. The paracrine factors were assessed by real-time PCR. Results: Transplantation of iMSC significantly restored the IAP/MAP in this CNI ED model and showed long-term effects. It could rescue the expression of vWF, eNOS, SMA, and Desmin, which indicated the alleviation of endothelial and smooth muscle tissues of the penis. iMSC therapy also could increase the expression of nNOS in the cavernosum and S100ß in the major pelvic ganglia (MPG) which contributed to the erectile function. Moreover, the level of BAX and caspase-3 were reduced and Bcl-2 was increased, which indicated the anti-apoptosis effects of iMSC. The iMSC showed little transdifferentiation and exerted their function by activating the secretome of the host. Conclusion: Transplantation of iMSC significantly improved ED induced by CNI. The iMSC may exert their effects via paracrine factors and may be a promising therapeutic candidate for treating CNI ED in the future.

MSC-derived exosomes ameliorate erectile dysfunction by alleviation of corpus cavernosum smooth muscle apoptosis in a rat model of cavernous nerve injury.

BACKGROUND: This study investigated the therapeutic effects of MSC-derived exosomes (MSC-Exos) on erectile function in a rat model of cavernous nerve injury (CNI). METHODS: MSCs were isolated from rat bone marrow and exosomes were isolated from the supernatants by ultracentrifugation. The tissue explant adherent method was used to isolate and culture corpus cavernosum smooth muscle cells (CCSMCs). MSCs and CCSMCs were identified by flow cytometry, in vitro differentiation or immunofluorescence staining. Thirty-two 10-week-old male Sprague Dawley (SD) rats were divided into four groups: a sham operation group and bilateral CNI groups that received intracavernosal (IC) injection of either PBS, MSCs or MSC-Exos. Four weeks after CNI and treatment, the erectile function of the rats was measured by electrically stimulating the cavernous nerve. The penile tissues were harvested for blinded histologic analysis and western blotting. H2O2 was used to induce apoptosis in the CCSMCs, and a flow cytometer was used to measure the cell viability of the CCSMCs treated with or without exosomes in vitro. RESULTS: Recovery of erectile function was observed in the MSC-Exos group. The MSC-Exos treatment significantly enhanced smooth muscle content and neuronal nitric oxide synthase in the corpus cavernosum. The ratio of smooth muscle to collagen in the corpus cavernosum was significantly improved in the MSC-Exos treatment group compared to the PBS vehicle group. WB confirmed these biological changes. Cell viability of the CCSMCs was increased in the MSC-Exos-treated groups, and caspase-3 expression was decreased after the MSC-Exos treatment in vivo and in vitro. CONCLUSIONS: Exosomes isolated from MSCs culture supernatants by ultracentrifugation could ameliorate CNI-induced ED in rats by inhibiting apoptosis in CCSMCs, with similar potency to that observed in the MSCs-treated group. Therefore, this cell-free therapy has great potential for application in the treatment of CNI-induced ED for replacing cell therapy. MSC-derived exosomes ameliorate erectile dysfunction in a rat model of cavernous nerve injury.

Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction.

BACKGROUND: Whether combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is more effective than transplantation of a single cell type in the restoration of erectile function is unknown. AIM: To investigate the effect of combined transplantation of MSCs and EPCs on restoration of erectile function in rats with cavernous nerve injury (CNI). METHODS: MSCs were isolated from human bone marrow and EPCs were isolated from human umbilical cord blood. MSCs and EPCs were identified by flow cytometry and in vitro differentiation or immunofluorescence staining. 25 8-week-old male Sprague-Dawley rats were allocated to 1 of 5 groups: sham operation group, bilateral CNI group receiving periprostatic implantation of MSCs plus EPCs, MSCs, EPCs, or phosphate buffered saline (control group). 2 weeks after CNI and treatment, erectile function of rats was measured by electrically stimulating the CN. The penis and major pelvic ganglia were harvested for histologic examinations. RNA and protein levels of neurotrophin factors (vascular endothelial growth factor, nerve growth factor, and brain-derived neurotrophic factor) in mono- or coculture MSCs and EPCs were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. OUTCOMES: Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. Histologic examinations of the penis and major pelvic ganglia and RNA and protein levels of neurotrophin factors in MSCs and EPCs were performed. RESULTS: MSCs and EPCs expressed the specified cell markers and exhibited the typical appearance and characteristics. Treatments using MSCs and/or EPCs could increase endothelial and smooth muscle contents of the corpus cavernosum, decrease caspase-3 expression and increase penile neuronal nitric oxide synthase expression, and restore the neural component of the major pelvic ganglia in rats with CNI. Combined transplantation of MSCs and EPCs had a better effect on improving erectile function than single transplantation of MSCs or EPCs. Expression levels of vascular endothelial growth factor and nerve growth factor in coculture MSCs and EPCs were significantly higher than those of primary MSCs or EPCs. CLINICAL TRANSLATION: Combined transplantation of MSCs and EPCs was more effective in restoring erectile function in CNI-related erectile dysfunction models. STRENGTHS AND LIMITATIONS: The study, for the 1st time, proved that combined transplantation of MSCs and EPCs was more effective in restoring erectile function in rats with CNI. The rat model might not represent the human condition. CONCLUSION: Combined periprostatic transplantation of MSCs and EPCs could restore erectile function in rats with CNI more effectively. MSCs might restore CN fibers by secreting neurotrophin factors such as vascular endothelial growth factor and nerve growth factor, and EPCs could enhance the paracrine activity of MSCs. Fang J-f, Huang X-n, Han X-y, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med 2018;15:284-295.