BioResearch Open Access最新文献

Central obesity (CO) is a defining characteristic of polycystic ovary syndrome (PCOS) and PCOS-induced disorders are likely to be exacerbated in the presence of CO. This study aims to evaluate the impact of CO on infertile women with PCOS undergoing in vitro fertilization (IVF).It is a retrospective and case-control study. One hundred eighty-eight infertile PCOS women undergoing IVF were divided into CO group (n = 70, waist circumference [WC] ≥80 cm) and noncentral obesity (NCO) group (n = 118, WC <80 cm). Baseline characteristics, parameters of ovarian stimulation and laboratory, and pregnancy outcomes were compared between two groups. After controlling for body mass index (BMI), WC positively correlated with fasting insulin (r = 0.210, p = 0.007), homeostatic model assessment for insulin resistance (r = 0.249, p = 0.006) and free androgen index (r = 0.249, p = 0.006). Compared with NCO group, CO group had significantly increased endocrine and metabolic disorders and needed significantly higher dose of gonadotropins, longer duration of ovarian stimulation (p < 0.05), but had significantly lower peak serum estradiol level (p < 0.01) and less oocytes retrieved (p = 0.032). CO group had significantly lower live birth and implantation rates (53.8% vs. 86.8%, p = 0.001; and 24.3% vs. 36.3%, p = 0.019, respectively) and higher early spontaneous miscarriage rate (38.5% vs. 7.5%, p = 0.002). For the multivariate analysis, by adjusting for age, BMI, insulin resistance, and hyperandrogenism (HA), CO was significantly independent risk factor for early miscarriage (adjusted relative ratio = 16.87, 95% confidence interval = 2.15-132.70, p = 0.007). CO is associated with insulin resistance, hyperinsulinemia, and HA independent of BMI and is associated with poor pregnancy outcome in infertile women with PCOS undergoing IVF.

Regenerative medicine has been growing because of the emergent need for tissues/organs for transplants and restorative surgeries. Biological scaffolds are important tools to try to solve this problem. The one used in this reserach was developed by an acellular biological scaffold from canine placenta with a rich source of cellular matrix. After decellularization, the cellular matrix demonstrated structural preservation with the presence of important functional proteins such as collagen, fibronectin, and laminin. We used cells transduced with vascular endothelial growth factor (VEGF) to recellularize this scaffold. It was succeeded by seeding the cells in nonadherent plaques in the presence of the sterelized placenta scaffold. Cells were adhered to the scaffold when analyzed by immunocytochemistry and scanning electron microscopy, both showing sprouting of yolk sac VEGF (YSVEGF) cells. This recellularized scaffold is a promissory biomaterial for repairing injured areas where neovascularization is required.

Hearing loss, the most common neurological disorder and the fourth leading cause of years lived with disability, can have profound effects on quality of life. The impact of this "invisible disability," with significant consequences, economic and personal, is most substantial in low- and middle-income countries, where >80% of affected people live. Given the importance of hearing for communication, enjoyment, and safety, with up to 500 million affected globally at a cost of nearly $800 billion/year, research on new approaches toward prevention and treatment is attracting increased attention. The consequences of noise pollution are largely preventable, but irreversible hearing loss can result from aging, disease, or drug side effects. Once damage occurs, treatment relies on hearing aids and cochlear implants. Preventing, delaying, or reducing some degree of hearing loss may be possible by avoiding excessive noise and addressing major contributory factors such as cardiovascular risk. However, given the magnitude of the problem, these interventions alone are unlikely to be sufficient. Recent advances in understanding principal mechanisms that govern hearing function, together with new drug discovery paradigms designed to identify efficacious therapies, bode well for pharmaceutical intervention. This review surveys various causes of loss of auditory function and discusses potential neurological underpinnings, including mitochondrial dysfunction. Mitochondria mitigate cell protection, survival, and function and may succumb to cumulative degradation of energy production and performance; the end result is cell death. Energy-demanding neurons and vestibulocochlear hair cells are vulnerable to mitochondrial dysfunction, and hearing impairment and deafness are characteristic of neurodegenerative mitochondrial disease phenotypes. Beyond acting as cellular powerhouses, mitochondria regulate immune responses to infections, and studies of this phenomenon have aided in identifying nuclear factor kappa B and nuclear factor erythroid 2-related factor 2/antioxidant response element signaling as targets for discovery of otologic drugs, respectively, suppressing or upregulating these pathways. Treatment with free radical scavenging antioxidants is one therapeutic approach, with lipoic acid and corresponding carnitine esters exhibiting improved biodistribution and other features showing promise. These compounds are also histone deacetylase (HDAC) inhibitors, adding epigenetic modulation to the mechanistic milieu through which they act. These data suggest that new drugs targeting mitochondrial dysfunction and modulating epigenetic pathways via HDAC inhibition or other mechanisms hold great promise.

Weight Cycling (WC) is a prevalent behavior associated with adverse cardiovascular (CV) health. However, a 2010 review on the effects of WC and blood pressure (BP) determined that there was not enough evidence to draw definitive conclusions. Central BP is the principal predictor of CV risk compared to peripheral BP. The influence that WC may have specifically on central BP is unknown. Cross-sectional observation of self-reported history of WC on measures of CV health was undertaken. Seventy-five women completed a Weight and Lifestyle Inventory questionnaire, which is considered a reliable index of WC (r = 0.87, p < 0.001). Measures of visceral fat, BP, arterial stiffness, and VO₂peak were taken. Regression equations were used to assess primary predictors of these outcomes. Seventy-five middle aged (39 ± 11 years), obese (32 ± 7 kg/m²), and relatively unfit (24 ± 8 ml·kg^-1 min^-1) women completed the study. Visceral fat was the strongest predictor of brachial systolic blood pressure (SBP; r² = 0.283), brachial diastolic blood pressure (DBP; r² = 0.176), central SBP (r² = 0.375), and augmentation index (AIx; r² = 0.535, all p < 0.001). VO₂peak was the strongest predictor of central DBP (r² = 0.062, p = 0.036) and augmentation pressure (AP; r² = 0.491, p < 0.001). Weight cycling index was associated with visceral fat (r = 0.521, p < 0.001). Visceral fat was a mediator between WC and central SBP (confidence interval [CI] = 0.0053-0.0602), AP (CI = 0.0507-0.4915), AIx (CI = 0.0025-0.0699), and carotid-femoral pulse wave velocity (CI = 0.0115-0.1227; all p < 0.05). WC may increase visceral fat accumulation, which was associated with increased central SBP and measures of arterial stiffness.

Prophylactic human papillomavirus (HPV) vaccination is the most effective preventive method against invasive cervical cancer, the second leading cause of cancer-related deaths among women in Bangladesh. Evidence on women's knowledge and perception about cervical cancer and HPV vaccination are needed for effective implementation of national cervical cancer prevention programs. The objective of this study was to assess the knowledge, attitude, and acceptance of cervical cancer, HPV, and HPV vaccination among urban professional women in Bangladesh. We recruited 160 female professionals employed at selected private banks in Bangladesh. Participants were selected using nonprobability-based convenience sampling for interviews through a self-administered questionnaire. Later, in-depth interviews were conducted with nine of these women. Quantitative data were analyzed utilizing descriptive statistics, whereas qualitative data were analyzed using a thematic approach. Ninety-eight percent of participants reported that they had previously heard of cervical cancer, however, only half (51%) reported to have heard of HPV as a cause of the disease. Less than 1% of the 160 participants had previously undergone a pap smear, and only 2% were vaccinated with at least one dose of HPV vaccination. Although knowledge was low, intention for acceptance of vaccination was moderate for women and high for their children. Although the majority of women had heard of cervical cancer, few women had in-depth knowledge of HPV and the etiology of invasive disease. This study draws attention to the urgent need of educational interventions on cervical cancer and its prevention to improve uptake of available HPV vaccination in Bangladesh.

Fatigue, stress, and depression contribute to poor health-related quality of life (HRQoL) among cancer survivors. This study examined the effects of combined aerobic and resistance training (CART) on HRQoL and biomarkers of stress. Cancer survivors (n = 76, 91% female, 39% breast cancer, 32% gynecologic cancer) were enrolled in CART for three 60-min sessions, weekly, for 26 weeks. Participants completed the National Institutes of Health's Patient Reported Outcomes Measurement Information System (NIH PROMIS) fatigue assessment and the SF-36. Cortisol and c-reactive protein (CRP) were assessed using volunteered blood specimens. Baseline fatigue scores were worse for participants completing treatment within the last year, compared to long-term survivors [F = (2, 59) = 3.470, p = 0.038]. After 26 weeks, fatigue scores improved by a noteworthy two points [M = 52.72, standard deviation, SD = 10.10 vs. M = 50.67, SD = 10.14; t(48) = 1.7145, p = 0.092]. Pre- to postintervention improvements in bodily pain [M = 50.54, SD = 9.51 vs. M = 48.20, SD = 10.07; t(33) = 2.913, p = 0.006] and limitations in social functioning [M = 50.60, SD = 9.17 vs. M = 47.75, SD = 11.66; t(33) = 2.206, p = 0.034], as well as a mean decrease of 1.64 ± 10.11 mg/L in CRP levels [t(107) = 1.261, p = 5.965], were observed. Participants within 1 year of treatment completion experienced greater improvements in post CRP levels compared to those who had treatment 1-4 years (p = 0.030) and 5 or more years ago (p = 0.023). Physical functioning, fatigue, fear/anxiety, social role satisfaction, and CRP levels improved following participation in this exercise intervention. Oncologists should consider recommending CART as soon as medically feasible following the cessation of cancer treatment.

Breast cancer is the most common malignancy among Arab women in Eastern Mediterranean Region (EMR). The incidence of breast cancer has substantially increased in recent years among this women population, especially those younger than 50, and the incidence is expected to double by 2030. Considerable experimental evidence supports the potential role of dietary habits and lifestyle in cancer etiology and cancer prevention. In this review we examined the literature for evidence to link dietary choices and the rise in incidence and mortality of breast cancer among women in EMR. A literature search was conducted in PubMed and Ovid MEDLINE databases up to December 2017. The search terms used are breast cancer prevalence, breast cancer incidence worldwide, breast cancer and: nutrition, protein intake, vitamin D intake, fat intake, phytoestrogens, EMR, Arab, Middle East, Gulf countries, the UAE Arab women, breast cancer risk, diet, and chemoprevention. We found evidence to suggest that there is an alarming epidemic of obesity among women in most of the EMR countries, especially Gulf Cooperation Council (GCC) countries. The rise in the new breast cancer cases among women could be attributed to excess body weight. Their dietary pattern, which correlates with obesity, can be an important factor in the etiology of cancer. Although very few studies were found to support a direct causal relationship between obesity and breast cancer in the EMR, circumstantial evidence clearly points to the possible role of the epidemic, obesity, in this population and the startling rise in cases of breast cancer. Well-designed and systematic studies are urgently needed to confirm these associations and to elucidate potential mechanisms. More urgently, calls to action are needed in many sectors and at all levels of society, to establish intensive strategies for reducing obesity and promoting an overall healthy diet. Continued and expanded research on diet, lifestyle, and breast cancer risk is urgently needed to build the foundation for future progress in evidence-based public health efforts.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known to activate the canonical NF-κB pathway similar to TNF. The exact mechanism of the entire signaling cascade is still under investigation. The involvement of linear ubiquitylation as upregulating component has already been shown recently in some cell lines, but not in human embryonic kidney 293 (HEK293) cells. The downregulating function of the ABIN-1 (A20 binding and inhibitor of NF-κB) as linear ubiquitylation antagonist has been shown in combination with some NF-κB-inducing pathways, but not with TRAIL. We performed luciferase and western blot assays using HEK293 cells stimulated with either TRAIL (or TNF as a control) to analyze the involvement of linear ubiquitin chain assembly complex (LUBAC) components and the impact of ABIN-1 and ABIN-1-MAD (truncated form without A20 binding site) on NF-κB signaling. For overexpression experiments, we added plasmids of ABIN-1 and ABIN-1-MAD or LUBAC components HOIP, HOIL-1, or SHARPIN (single and combinations). For downregulation experiments five pairs of either SHARPIN, HOIL-1, or HOIP targeting miRNAs or one miRNA for ABIN-1 were designed and added. ABIN-1 and its truncated form ABIN-1-MAD reduced the NF-κB induction significantly indicating its involvement as antagonist (independent of deubiquitinase A20) of linear ubiquitylation in TRAIL-induced NF-κB signaling. In opposition, knockdown of ABIN-1 using a specific ABIN-1 miRNA led a clear increase of NF-κB signaling. Addition of single LUBAC components or combinations (except for SHARPIN with HOIL-1) resulted in clearly stronger NF-κB inductions. MiRNAs targeting LUBAC components significantly reduced NF-κB activation. Thus, in HEK293 cells linear ubiquitylation by LUBAC critically upregulates and ABIN-1 downregulates TRAIL-induced NF-κB signaling and may be interesting targets for future pathological therapies.

The precision health initiative is leading the discovery of novel biomarkers as important indicators of biological processes or responses to behavior, such as physical activity. Neural biomarkers identified by magnetic resonance imaging (MRI) hold promise to inform future research, and ultimately, for transfer to the clinical setting to optimize health outcomes. This study investigated resting-state and functional brain biomarkers between midlife women who were maintaining physical activity in accordance with the current national guidelines and previously acquired age-matched sedentary controls. Approval was obtained from the Human Subjects Committee. Participants included nondiabetic, healthy weight to overweight (body mass index 19-29.9 kg/m²) women (n = 12) aged 40-64 years. Control group data were used from participants enrolled in our previous functional MRI study and baseline resting-state MRI data from a subset of sedentary (<500 kcal of physical activity per week) midlife women who were enrolled in a 9-month exercise intervention conducted in our imaging center. Differential activation of the inferior frontal gyrus (IFG) and greater connectivity with the dorsolateral prefrontal cortex (dlPFC) was identified between physically active women and sedentary controls. After correcting for multiple comparisons, these differences in biomarkers of physical activity maintenance did not reach statistical significance. Preliminary evidence in this small sample suggests that neural biomarkers of physical activity maintenance involve activations in the brain region associated with areas involved in implementing goal-directed behavior. Specifically, activation of the IFG and connectivity with the dlPFC is identified as a neural biomarker to explain and predict long-term physical activity maintenance for healthy aging. Future studies should evaluate these biomarker links with relevant clinical correlations.