Potential Roles of mtDNA Mutations in PCOS-IR: A Review.

Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disease that affecting females in reproductive age. Insulin resistance (IR), an important molecular basis for PCOS, accounts for at least 75% of women carrying this syndrome. Although there have been many studies on PCOS-IR, the detailed mechanisms are not fully understood. As essential hub for energy generation, mitochondria are critical to insulin secretion and normal function, whereas mutations in mitochondrial DNA (mtDNA) result in mitochondrial dysfunctions contributing to the pathophysiology of PCOS-IR via the regulation of balance of oxidative stress (OS), energy deficiency, or hormone metabolism. In the current review, we summarize the clinical and molecular features of PCOS-IR and discuss molecular mechanisms related to mtDNA mutations.

Peripheral-Free Calibration Method for Redundant IMUs Based on Array-Based Consumer-Grade MEMS Information Fusion.

The MEMS array-based inertial navigation module (M-IMU) reduces the measurement singularities of MEMS sensors by fusing multiple data processing to improve its navigation performance. However, there are still existing random and fixed errors in M-IMU navigation. The calibration method calibrates the fixed error parameters of M-IMU to further improve navigation accuracy. In this paper, we propose a low-cost and efficient calibration method to effectively estimate the fixed error parameters of M-IMU. Firstly, we manually rotate the M-IMU in multiple sets of different attitudes (stationary), then use the LM-calibration algorithm to optimize the cost function of the corresponding sensors in different intervals of the stationary-dynamic filter separation to obtain the fixed error parameters of MEMS, and finally, the global fixed error parameters of the M-IMU are calibrated by adaptive support fusion of the individual MEMS fixed error parameters based on the benchmark conversion. A comparison of the MEMS calibrated separately by the fusion-calibration algorithm and the LM-calibration algorithm verified that the calibrated MEMS array improved the measurement accuracy by about 10 db and reduced the dispersion of the output data by about 8 db compared to the individual MEMS in a multi-dimensional test environment, indicating the robustness and feasibility of the fusion calibration algorithm.

Clinical profiles and outcomes of acute type A aortic dissection and intramural hematoma in the current era: lessons from the first registry of aortic dissection in China.

BACKGROUND: Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. METHODS: All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. RESULTS: A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%). CONCLUSIONS: Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.

Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin.

Diabetes mellitus (DM) increases myocardial oxidative stress and endoplasmic reticulum (ER) stress. Melatonin confers cardioprotective effect by suppressing oxidative damage. However, the effect and mechanism of melatonin on myocardial ischemia-reperfusion (MI/R) injury in type 2 diabetic state are still unknown. In this study, we developed high-fat diet-fed streptozotocin (HFD-STZ) rat, a well-known type 2 diabetic model, to evaluate the effect of melatonin on MI/R injury with a focus on silent information regulator 1 (SIRT1) signaling, oxidative stress, and PERK/eIF2α/ATF4-mediated ER stress. HFD-STZ treated rats were exposed to melatonin treatment in the presence or the absence of sirtinol (a SIRT1 inhibitor) and subjected to MI/R surgery. Compared with nondiabetic animals, type 2 diabetic rats exhibited significantly decreased myocardial SIRT1 signaling, increased apoptosis, enhanced oxidative stress, and ER stress. Additionally, further reduced SIRT1 signaling, aggravated oxidative damage, and ER stress were found in diabetic animals subjected to MI/R surgery. Melatonin markedly reduced MI/R injury by improving cardiac functional recovery and decreasing myocardial apoptosis in type 2 diabetic animals. Melatonin treatment up-regulated SIRT1 expression, reduced oxidative damage, and suppressed PERK/eIF2α/ATF4 signaling. However, these effects were all attenuated by SIRT1 inhibition. Melatonin also protected high glucose/high fat cultured H9C2 cardiomyocytes against simulated ischemia-reperfusion injury-induced ER stress by activating SIRT1 signaling while SIRT1 siRNA blunted this action. Taken together, our study demonstrates that reduced cardiac SIRT1 signaling in type 2 diabetic state aggravates MI/R injury. Melatonin ameliorates reperfusion-induced oxidative stress and ER stress via activation of SIRT1 signaling, thus reducing MI/R damage and improving cardiac function.

cIAP1 attenuates shear stress-induced hBMSC apoptosis for tissue-engineered blood vessels through the inhibition of the mitochondrial apoptosis pathway.

AIMS: Shear stress-induced apoptosis is one of the leading problems in seeding cells of tissue-engineered blood vessels (TEBVs). We aim to determine the human bone mesenchymal stem cell (hBMSC) apoptosis under shear stress and its possible mechanism. MAIN METHODS: hBMSCs were subjected to 3-, 10-, and 30-dyn/cm(2) shear stress in vitro. Cell multiplication and apoptosis were analyzed by flow cytometry. Apoptosis-related genes were screened by a microarray and evidenced by real-time polymerase chain reaction (RT-PCR). hBMSCs were treated with the human recombinant cell inhibitor of apoptosis protein 1 (cIAP1) and its inhibitor, direct IAP-binding protein with low pl (DIABLO), and then cell apoptosis was analyzed. KEY FINDINGS: Exposure to shear stress (3dyn/cm(2) for >6h) activated apoptosis progress of hBMSCs. However, the same degree of shear stress (3dyn/cm(2) for 6h) did not induce apoptosis. Microarray screening and RT-PCR revealed that Bcl-2-related ovarian killer (BOK) and apoptotic protease-activating factor 1 (APAF1), key molecules of the mitochondrial apoptosis pathway, were markedly upregulated under 3-dyn/cm(2) shear stress. Then, we observed that cIAP1, a Caspase 9 inhibitor, was elevated under 3dyn/cm(2) at short-time exposure (2 or 6h), and it was reduced at long-time exposure (24h). When treated with human recombinant cIAP1, Caspase 3 activity and LDH release of hBMSCs were decreased, and vice versa when treated with DIABLO. SIGNIFICANCE: cIAP1 attenuates hBMSC apoptosis when cells were exposed to shear stress through the regulation of the BOK-APAF1-Caspase 9-Caspase 3 pathway. It may present a pharmacological target to enhance hBMSC biological function in the application of TEBVs.

[Comparison study between Vecchietti's and Davydov's laparoscopic vaginoplasty in Mayer-Rokitansky-Küster-Hauser syndrome].

OBJECTIVE: To compare Vecchietti's and Davydov's laparoscopic techniques for vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. METHODS: From January 2010 to December 2013, 13 patients underwent the Vecchietti's laparoscopic procedure (Vecchietti group), and 15 patients underwent the Davydov's laparoscopic procedure (Davydov group). Intraoperative parameters and postoperative results were compared. RESULTS: Both of the two groups were successfully treated. The neovagina in both groups were wide with good elasticity, softness and smoothness. The operation time [(39±7) versus (73±11) minutes], the intraoperative blood loss [(21±6) versus (63±10) ml], the anal exsufflation time after surgery [(19±5) versus (28±6) hours] and the recovery period of body temperature after surgery [(35±10) versus (46±10) hours] of the Vecchietti group were less than those of the Davydov group (all P<0.05). But the neovagina length [(8.8±0.5) versus (9.6±0.5) cm] was shorter and the Female Sexual Function Index scale score [26.8±2.0 versus 28.5±1.7] was lower in the Vecchietti group than those in the Davydov group (all P<0.05). The postoperation hospital duration didn't reached statistical difference between the two groups [(7.5±0.9) versus (7.1±0.7) days, P>0.05]. No intraoperative complication occurred. After surgery, 2 patients were found vaginal polyps and 8 patients were suffered from pain in the Davydov group, while all patients were suffered from pain in the Vecchietti group. CONCLUSIONS: Both Vecchietti's and Davydov's laparoscopic techniques are simple, safe and effective surgical methods for vaginal reconstruction. In contrast, the Vecchietti's procedure is more time efficient and minimally invasive, while the Davydov's procedure can get less pain, longer vagina and higher sexual satisfaction.

Proteomic profiling of human bone marrow mesenchymal stem cells under shear stress.

Mesenchymal stem cells (MSCs) are promising seed cells for tissue engineering of blood vessels. As seed cells, MSCs must endure blood fluid shear stress after transplantation. It has been shown that fluid shear stress can regulate the proliferation and differentiation of MSCs. However, the effects of fluid shear stress on MSCs including the types of proteins modulated are still not well understood. In this study, we exposed human mesenchymal stem cells (HMSCs) to 3 dyn/cm(2) shear stress for 6 h and compared them to a control group using proteomic analysis. Thirteen specific proteins were affected by shear stress, 10 of which were up-regulated. Shear stress especially induced sustained increases in the expression of Annexin A2 and GAPDH, which have been specifically shown to affect HMSCs function. We present here the first comparative proteome analysis of effect of shear stress on HMSCs.

RGD-modified acellular bovine pericardium as a bioprosthetic scaffold for tissue engineering.

Acellular biological tissues, including bovine pericardia (BP), have been proposed as natural biomaterials for tissue engineering. However, small pore size, low porosity and lack of extra cellular matrix (ECM) after native cell extraction directly restrict the seed cell adhesion, migration and proliferation and which is a vital problem for ABP's application in the tissue engineered heart valve (TEHV). In the present study, we treated acellular BP with acetic acid, which increased the scaffold pore size and porosity and conjugated RGD polypeptides to ABP scaffolds. After 10 days of culture in vitro, the human mesenchymal stem cells (hMSCs) attached the best and proliferated the fastest on RGD-modified acellular scaffolds, and the cell has grown deep into the scaffold. In contrast, a low density of cells attached to the unmodified scaffolds, with few infiltrating into the acellular tissues. These findings support the potential use of modified acellular BP as a scaffold for tissue engineered heart valves.