Atherosclerosis is an inflammatory process due to oxidized low-density lipoprotein (oxLDL) accumulation in macrophages. We investigated the involvement of microRNAs in oxLDL accumulation and ...inflammatory response in macrophages. The expression of miR-146a decreases under oxLDL stimulation. MiR-146a significantly reduces intracellular LDL cholesterol content and secretion of interleukin 6, interleukin 8, chemokine (C–C motif) ligand 2 and matrix metallopeptidase 9. Toll-like receptor 4 (TLR4) is a relevant target of miR-146a, and miR-146a inhibits the activation of TLR4-dependent intracellular signaling pathways involved in cytoskeleton rearrangement, lipid uptake, and inflammatory cytokine secretion. These results indicate that miR-146a contributes to the regulation of both oxLDL accumulation and inflammatory response by negatively regulating TLR4 and thereby inhibiting the activation of TLR4-dependent signaling pathways. Over-expression of miR-146a may be useful in the prevention and treatment of atherosclerosis.
This study aims to investigate the effect of different local testicular treatments and validate common prognostic factors on primary testicular lymphoma (PTL) patients. We retrospectively reviewed ...the clinical records of 32 patients from 1993 to 2017 diagnosed with PTL and included 22 patients for analysis. The Kaplan-Meier method, Log-rank test, and multivariate Cox proportional hazard regression analysis were applied to evaluate progression-free survival (PFS), overall survival (OS), and determine prognosis predictors. The median follow-up time was 30 months. Median OS and PFS were 96 months and 49 months, respectively. In univariate analysis, advanced Ann Arbor stage (III/IV) (P < 0.001), B symptoms (P < 0.001), and extranodal involvement other than testis (P = 0.001) were significantly associated with shorter OS and PFS. In multivariate analysis, Ann Arbor stage was significantly associated with OS (OR = 11.58, P = 0.049), whereas B symptom was significantly associated with PFS (OR = 11.79, P= 0.049). In the 10 patients with the systemic usage of rituximab, bilateral intervention could improve median OS from 16 to 96 months (P = 0.032). The study provides preliminary evidence on bilateral intervention in testes in the rituximab era and validates common prognostic factors for Chinese PTL patients.
Osteoporosis is a systemic skeletal disorder characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue. The World Health Organization has defined osteoporosis as a ...decrease in bone mass (50%) and bony quality (50%). Vitamin D, a steroid hormone, is crucial for skeletal health and in mineral metabolism. Its direct action on osteoblasts and osteoclasts and interaction with nonskeletal tissues help in maintaining a balance between bone turnover and bone growth. Vitamin D affects the activity of osteoblasts, osteoclasts, and osteocytes, suggesting that it affects bone formation, bone resorption, and bone quality. At physiological concentrations, active vitamin D maintains a normal rate of bone resorption and formation through the RANKL/OPG signal. However, active vitamin D at pharmacological concentration inhibits bone resorption at a higher rate than that of bone formation, which influences the bone quality and quantity. Nutritional vitamin D rather than active vitamin D activates osteoblasts and maintains serum 25(OH)D3 concentration. Despite many unanswered questions, much data support nutritional vitamin D use in osteoporosis patients. This article emphasizes the role of nutritional vitamin D replacement in different turnover status (high or low bone turnover disorders) of osteoporosis together with either anti-resorptive (Bisphosphonate, Denosumab et.) or anabolic (Teriparatide) agents when osteoporosis persists.
•Osteoporosis is composed by quality and quantity of bone mass.•Treatment for osteoporosis should be focused on the bone turnover rate in order to normalize the bone remodeling.•Nutritional vitamin D is an important regulator to maintain the bone remodeling due to its pleotropic effect.
Abstract In the meiotic prophase, programmed SPO11‐linked DNA double‐strand breaks (DSBs) are repaired by homologous recombination (HR). The MRE11‐RAD50‐NBS1 (MRN) complex is essential for initiating ...DNA end resection, the first step of HR. However, residual DNA end resection still occurs in Nbs1 knockout (KO) spermatocytes for unknown reasons. Here, we show that DNA end resection is completely abolished in Mre11 KO spermatocytes. In addition, Mre11 KO, but not Nbs1 KO, undifferentiated spermatogonia are rapidly exhausted due to DSB accumulation, proliferation defects, and elevated apoptosis. Cellular studies reveal that a small amount of MRE11 retained in the nucleus of Nbs1 KO cells likely underlies the differences between Mre11 and Nbs1 KO cells. Taken together, our study not only demonstrates an irreplaceable role of the MRE11 in DNA end resection at SPO11‐linked DSBs but also unveils a unique function of MRE11 in maintaining the long‐term viability of undifferentiated spermatogonia.
White matter lesions induced by chronic cerebral hypoperfusion are associated with cognitive impairment in vascular dementia (VaD). Previous studies have shown that acupuncture can ameliorate the ...cognitive deficits of individuals with VaD. However, the neuroimaging mechanisms of acupuncture on white matter perfusion and integrity remain elusive. In this study, the VaD model was induced by bilateral common carotid arteries occlusion (BCCAO) in rats. Novel object recognition task and Morris water maze were performed to evaluate short-term memory and spatial learning and memory. Arterial spin labeling and diffusion tensor imaging (DTI) were used to measure the cerebral blood flow (CBF) and the white matter integrity. Pathological examinations detected the myelin loss and concomitant neuroinflammation. The results demonstrate that BCCAO rats with reduced CBF exhibited worse performance and altered DTI parameters, including decreased fractional anisotropy, increased radial diffusivity, and axial diffusivity in white matter regions. Acupuncture ameliorated cognitive impairment, increased CBF, and protected the myelin sheath integrity but not the axons of BCCAO rats. These protective effects of acupuncture on white matter were significantly correlated with improved CBF. Pathological examination confirmed that the loss of myelin basic protein and microglial accumulation associated IL-1β and IL-6 production were attenuated by acupuncture treatment. Our findings suggest that acupuncture protects cognitive function of BCCAO rats by improving white matter perfusion and integrity.
Abstract Objective To explore the reliability and accuracy of lung ultrasound for diagnosing neonatal pneumothorax. Methods This study was divided into two phases. (1) In the first phase, from ...January 2013 to June 2015, 40 patients with confirmed pneumothorax had lung ultrasound examinations performed to identify the sonographic characteristics of neonatal pneumothorax. (2) In the second phase, from July 2015 to August 2016, lung ultrasound was undertaken on 50 newborn infants with severe lung disease who were suspected of having pneumothorax, to evaluate the sonographic accuracy and reliability to diagnose pneumothorax. Results (1) The main ultrasonic manifestations of pneumothorax are as follows: ① lung sliding disappearance, which was observed in all patients (100%); ② the existence of the pleural line and the A-line, which was also observed in all patients (100%); ③ the lung point, which was found in 75% of the infants with mild-moderate pneumothorax but not found to exist in 25% of the severe pneumothorax patients; ④ the absence of B-lines in the area of the pneumothorax (100% of the pneumothorax patients); and ⑤ no lung consolidation existed in the area of the pneumothorax (100% of the pneumothorax patients). (2) The accuracy and reliability of the lung sonographic signs of lung sliding disappearance as well as the existence of the pleural line and the A-line in diagnosing pneumothorax were as follows: 100% sensitivity, 100% specificity, 100% positive predictive value, and 100% negative predictive value. When the lung point exists, the diagnosis is mild-moderate pneumothorax, whereas if no lung point exists, the diagnosis is severe pneumothorax. Conclusion Lung ultrasound is accurate and reliable in diagnosing and ruling out neonatal pneumothorax and, in our study, was found to be as accurate as chest X-ray.
There has been growing research interest in developing methodology to evaluate healthcare centers' performance with respect to patient outcomes. Conventional assessments can be conducted using fixed ...or random effects models, as seen in provider profiling. We propose a new method, using fusion penalty to cluster healthcare centers with respect to a survival outcome. Without any prior knowledge of the grouping information, the new method provides a desirable data‐driven approach for automatically clustering healthcare centers into distinct groups based on their performance. An efficient alternating direction method of multipliers algorithm is developed to implement the proposed method. The validity of our approach is demonstrated through simulation studies, and its practical application is illustrated by analyzing data from the national kidney transplant registry.
Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes ...to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats.
In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl's staining. The expressions of β-CTX and osteocalcin were assessed by ELISA.
It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group.
In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.
This review investigates the mechanisms of bioactive glass on the management of dental caries. Four databases (PubMed, Web of Science, EMBASE (via Ovid), Medline (via Ovid)) were systematically ...searched using broad keywords and terms to identify the literature pertaining to the management of dental caries using "bioactive glass". Titles and abstracts were scrutinized to determine the need for full-text screening. Data were extracted from the included articles regarding the mechanisms of bioactive glass on dental caries management, including the aspect of remineralizing effect on enamel and dentine caries, and antimicrobial effect on cariogenic bacteria. After removal of duplicates, 1992 articles were identified for screening of the titles and abstracts. The full texts of 49 publications were scrutinized and 23 were finally included in this review. Four articles focused on the antimicrobial effect of bioactive glass. Twelve papers discussed the effect of bioactive glass on demineralized enamel, while 9 articles investigated the effect of bioactive glass on demineralized dentine. In conclusion, bioactive glass can remineralize caries and form apatite on the surface of enamel and dentine. In addition, bioactive glass has an antibacterial effect on cariogenic bacteria of which may help to prevent and arrest dental caries.
Biomass-derived levulinic acid (LA) and its esters are currently envisaged as versatile, renewable platform chemicals. In this study, cellulosic pulp derived from the cooking of lignocellulosic ...biomass with active oxygen and solid alkali was employed as raw material for the formation of LA or ethyl levulinate (EL). This pretreatment process is highly effective for the delignification and deconstruction of lignocellulose matrix, making a facile degradation of the resulting cellulosic pulp to LA or EL. At this point, the acid-catalyzed hydrolysis or ethanolysis of cellulosic pulp was optimized by response surface methodology (RSM), offering desirable LA yield of 65.3% or EL yield of 62.7%, which is significantly higher than those obtained from raw biomass. More importantly, coking behavior on the inwall of the reactor was eliminated during the hydrolysis or ethanolysis of cellulosic pulp, which is one of the top challenges for the acid-catalyzed conversion of biomass in an industrial scale.
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