Clinical research advances of CFHR5 nephropathy: a recent review.

CFHR5 nephropathy is a type of clinical C3 glomerulopathy, which is a monogenic genetic disease caused by the internal replication of CFHR5 gene, a protein related to the complement regulatory factor H family. The disease seems to be prevalent only in people of Greek Cypriot descent. Because of the special variation of the internal replication of exon 2 and exon 3 of CFHR5 protein in the occurrence of disease, it has had a serious impact on local residents. At present, the mechanism of glomerular damage caused by CFHR5 protein mutations is still unclear. The purpose of this article is to review the clinical research advances of this disease in the past 10 years, including the study of mutant genes, the analysis of mutant proteins and the role of alternative pathways in glomerular injury. It covers the progress in diagnosis and clinical treatment of the disease and looks forward to the future development prospects of its treatment. It is hoped that the recent results will be summarized for the follow-up in-depth study of CFHR5 nephropathy.

MRI findings for diagnosis of postoperative foreign body granulomas versus recurrent tumours in patients of brain tumour surgery.

AIM: To evaluate the postoperative magnetic resonance imaging (MRI) findings of intracranial foreign body granulomas (FBGs) and true recurrent tumours (RTs) and thus lead to a basis for management decision-making. MATERIALS AND METHODS: Twenty-two patients with previous brain tumour surgery were diagnosed clinically with RT and underwent surgery. Re-operative pathology revealed FBG in eight patients and RT in 14 patients. MRI findings before the initial operation were compared to those before the re-operation. RESULTS: Features of FBGs versus RTs on MRI were as follows: (1) mean lesion size: 1.3 ± 0.7 (0.5-2.6) versus 3.2 ± 1.7 (1.1-6.3) cm (p=0.001, odds ratio [OR] = 4.18); (2) hypointensity on T2-weighted imaging (WI): 6/8 (75%) versus 0/14 (0%; p<0.001, OR=75.4); (3) non-restricted diffusion on diffusion-WI (DWI): 6/8 (75%) versus 2/14 (14.3%; p=0.008, OR=18); and (4) "ring and bubble" appearance on contrast-enhanced T1WI: 7/8 (87.5%) versus 2/14 (14.3%; p=0.001, OR=42). In comparison with their original tumours, the FBGs in the FBG group showed significantly lower T2 signal intensity, lower signal on DWI, and more cases of non-restricted diffusion on DWI (p=0.04, 0.04, 0.04, respectively). CONCLUSION: On brain MRI, FBGs can be differentiated from RTs by their relatively smaller size, hypointensity on T2WI, lack of restricted diffusion on DWI, and "ring and bubble" appearance on contrast-enhanced T1WI. Comparing the MRI findings of the focal lesion in the tumour bed with those of the original tumour is suggested to enhance diagnostic confidence.

Anatomical characteristics of maxillary sinus antroliths and their influence on sinus membrane thickness: a retrospective cone beam computed tomography analysis.

The purpose of this study was to assess the anatomy of antroliths and its influence on the thickness of the maxillary sinus membrane. Cone beam computed tomography (CBCT) was performed on 239 patients (478 sinuses). The prevalence of antroliths per sinus was 8.4%. Regarding their distribution, antroliths were predominantly unilateral (82.5%), single (67.5%), and in a dentate area (60.0%). The antroliths were mainly located in the molar region (95.0%) and in the sinus floor (77.5%). The measured dimensions of the antroliths were as follows: length 5.6±4.4mm, width 4.1±2.9mm, height 3.5±2.1mm. The relationships between the antroliths and the sinus membrane (type 1, 34.1%; type 2, 52.3%; type 3, 13.6%) indicated that sinus membranes tended to encircle antroliths, which resulted in a gradual increase in membrane thickness. The sinus membrane was found to be significantly thicker in the presence of antrolith(s) (P<0.001). Antroliths which are sufficiently large or are located adjacent to the sinus floor or lateral wall increase the risk of sinus membrane perforation during sinus augmentation procedures. Therefore, a thorough CBCT evaluation is needed to minimize the risk of complications prior to sinus augmentation procedures.

T2 mapping histogram at extraocular muscles for predicting the response to glucocorticoid therapy in patients with thyroid-associated ophthalmopathy.

AIM: To evaluate the performance of T2 mapping histograms at the extraocular muscles (EOMs) in predicting the response to glucocorticoid therapy in the patients with active and moderate-severe thyroid-associated ophthalmopathy (TAO). MATERIALS AND METHODS: Thirty active and moderate-severe TAO patients (responsive group, n=20; unresponsive group, n=10) were enrolled, and evaluated using T2 mapping before treatment. Histogram parameters (mean, median, max, min, 10th, 90th percentiles, skewness, and kurtosis) of T2 relaxation time (T2RT) at the EOMs for each orbit, and clinical variables (age, sex, disease duration, anti-thyroid treatment, smoking habit, pre-treatment thyroid function, thyrotrophin receptor antibody, diplopia presence, activity and severity scores) were collected and compared between groups. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to assess the predictive value of identified independent variables for treatment response. RESULTS: The responsive group showed significantly shorter disease duration (p=0.003), while higher T2RTmin than unresponsive group (p<0.001). Multivariate analysis showed that T2RTmin and disease duration were independent predictors for responsive TAOs. ROC curve analyses indicated that setting a cut-off value of ≥54.3 for T2RTmin demonstrated the optimal predicting specificity for responsive TAOs (100%), while a combination of T2RTmin ≥54.3 and disease duration ≤4.5 showed optimal predicting efficiency and sensitivity (area under the curve, 0.820; sensitivity, 65%). CONCLUSIONS: Histogram analysis can help to exhibit the heterogeneity of T2RT at the EOMs. T2RTmin, together with disease duration may be the promising marker for predicting response to glucocorticoid therapy in the patients with active and moderate-severe TAO.

Clinical significance of miR-492 in peripheral blood of acute myocardial infarction.

OBJECTIVE: To detect the potential of microRNA-492 (miR-492) as a diagnostic biomarker of acute myocardial infarction (AMI) in the acute phase. PATIENTS AND METHODS: A total of 100 AMI patients and 100 controls (non-AMI patients with chest pain) were retrospectively analyzed. Blood samples were collected at 0, 6, 12, and 24 h after admission, followed by detection of the serum miR-492 level. Serum levels of cTnI and creatine kinase-MB (CK-MB) in AMI patients were examined by enzyme-linked immunosorbent assay (ELISA). The potential relationship between miR-492 level with cTnI and CK-MB levels was analyzed by Pearson correlation test. Moreover, diagnostic value of miR-492 was assessed by depicting receiver operating characteristic (ROC) curves. RESULTS: Serum level of miR-492 achieved the peak at 6 h after admission, which was time-dependently reduced at 12 h and 24 h.  Serum levels of cTnI and CK-MB were higher in AMI patients than those of controls. However, miR-492 level achieved the peak before cTnI and CK-MB increased to the highest levels. MiR-492 level was positively correlated to cTnI and CK-MB levels. ROC curves verified the diagnostic value of miR-492 in AMI (AUC=0.8621, 95% CI=0.8129-0.9112, sensitivity=80%, specificity=75%). CONCLUSIONS: Serum level of miR-492 remarkably increases in the acute phase of AMI, which may be used as an effective biomarker for diagnosing AMI.

Morphological and microstructural brain changes in thyroid-associated ophthalmopathy: a combined voxel-based morphometry and diffusion tensor imaging study.

PURPOSE: To explore the morphological and microstructural changes of grey and white matter in the patients of thyroid-associated ophthalmopathy (TAO). METHODS: Twenty-five TAO patients and 25 well-matched healthy controls were recruited. Structural T1- and diffusion-weighted magnetic resonance imaging data were analyzed using voxel-based morphometry and voxel-based analysis of diffusion tensor imaging. RESULTS: Compared with healthy controls, TAO group showed significantly decreased grey matter volume in the brain region of the right middle frontal gyrus. Meanwhile, TAO group showed significantly decreased fractional anisotropy (FA), but increased mean, axial and radial diffusivities in the brain regions of the right superior occipital gyrus, middle occipital gyrus and cuneus in TAO group. In addition, the FA value in significant brain regions showed a positive correlation with visual acuity (r = 0.456, P = 0.025) and a negative correlation with disease duration (r = - 0.609, P = 0.003). CONCLUSION: Significant morphological and microstructural abnormalities in areas corresponding to known functional deficits of vision and cognition could be found in TAO patients. These results extended our understanding of neural relationships with TAO.

Dipeptidyl peptidase-4 inhibitor treatment could decrease chronic rhinosinusitis in diabetic patients.

AIM: To evaluate the relationship between dipeptidyl peptidase-4 inhibitor (DPP4i) treatment and chronic rhinosinusitis (CRS) in diabetic patients. METHODS: We used the Longitudinal Health Insurance Database for this population-based and population-matched cohort design study. Chi-square and Wilcoxon rank-sum tests were used to evaluate the association between categorical and continuous variables, respectively. The Kaplan-Meier method with the log-rank test was used to estimate the risk of CRS and DPP4i users. RESULTS: A total of 6198 diabetic patients were included in this cohort study. DPP4i users had a lower risk of developing CRS. The risk of CRS was significantly lower in women, patients with a Diabetes Complications Severity Index score higher than 4, patients with comorbidities, and patients with higher cumulative defined daily dose in the DPP4i group. CONCLUSION: The results of our study demonstrate that the use of DPP4i treatment could decrease CRS risk in diabetic patients in Taiwan.

MiR-15b ameliorates SONFH by targeting Smad7 and inhibiting osteogenic differentiation of BMSCs.

OBJECTIVE: The aim of this study was to explore the role of micro ribonucleic acid (miR)-15b in steroid-induced osteonecrosis of the femoral head (SONFH) and its potential mechanism. PATIENTS AND METHODS: Bone marrow tissues were collected from 5 patients with glucocorticoid (GC)-induced ONFH (GC-ONFH, GC group) and 5 patients with secondary ONFH (control group) undergoing total hip replacement in our hospital from July 2016 to August 2017. Subsequently, bone marrow mesenchymal stem cells (BMSCs) were separated from bone marrow extracted and cultured in vitro. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) assay was used to detect differentially expressed miRNAs in BMSCs of patients in GC group and control group. BMSCs were treated with different concentrations of GC. Next, the effect of GC on tmiR-15b expression level was detected via qRT-PCR. Alizarin red staining assay was performed to evaluate the effect of miR-15b on osteogenic differentiation of BMSCs. Meanwhile, the potential targets of miR-15b were predicted using bioinformatics software and validated through luciferase reporter gene assay, respectively. Additionally, Western blotting was conducted to determine the effect of miR-15b on the protein expression of the transforming growth factor beta (TGF-ß) signaling pathway. RESULTS: Flow cytometry demonstrated that the proportion of cluster of differentiation 44 (CD44)-positive cells was 99.7%, while that of CD45-positive cells was only 0.17% in cultured BMSCs. This suggested that the purity of BMSCs was relatively high. QRT-PCR assay indicated that the expression level of miR-15b declined significantly in BMSCs of GC group when compared with control group (p<0.01). The osteogenic differentiation capacity of BMSCs was significantly strengthened in GC group compared with control group (p<0.01). Subsequent qRT-PCR assay revealed that GC down-regulated the expression level of miR-15b in a dose-dependent manner. Besides, the osteogenic differentiation capacity of cells was remarkably strengthened in miR-15b mimic treatment group when compared with control group (p<0.01). Bioinformatics software (TargetScan) predicted that drosophila mothers against decapentaplegic protein 7 (Smad7) might be a potential target of miR-15b, which was indicated by luciferase reporter gene assay. In comparison with control group, miR-15b mimic treatment group exhibited significantly down-regulated protein expression level of Smad7, increased expression level of phosphorylated (p)-Smad2/3 and up-regulated messenger RNA (mRNA) expression level of runt-related transcription factor 2 (Runx2). However, the protein expression level of Smad7 and p-Smad2/3 and the mRNA expression level of Runx2 exhibited opposite trends in miR-15b inhibitor treatment group. CONCLUSIONS: MiR-15b relieves SONFH by targeting Smad7 and repressing osteogenic differentiation of BMSCs.

Ten-year fracture risk by FRAX and osteoporotic fractures in patients with systemic autoimmune diseases.

The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients' 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.

The MTase15 regulates reproduction in the wing-dimorphic planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).

S-Adenosyl-l-methionine-dependent methyltransferases (SAMMTases) modulate important cellular and metabolic activities in both prokaryotes and eukaryotes. Here, we functionally characterized an SAMMTase gene (MTase15) in the migratory brown planthopper (BPH), Nilaparvata lugens, which is the most notorious rice pest in Asia. The cDNA sequence of MTase15 is 2764 nt in length with an open reading frame of 1218 nt encoding 405 amino acid residues. Quantitative real-time PCR analysis showed that MTase15 was readily detected from egg to adult stages and extensively distributed in various body parts of adult females and males, with slightly high levels in ovary and testis, respectively. In addition, MTase15 was transcriptionally regulated by the insulin signalling pathway in BPH. RNA-interference-mediated knockdown of MTase15 (dsMtase15) resulted in deficiencies in vitellogenin synthesis and oogenesis, and female infertility. Males with Mtase15 knockdown retained the capability of producing sperms with normal viability, but less sperm was transferred to wild-type (wt) females during copulation, and eggs laid by these wt females arrested embryogenesis. These findings not only assign a functional role to MTase15, but also provide a link between the insulin signalling pathway and epigenetic regulation in BPH reproduction.

LncRNA GAPLINC promotes the growth and metastasis of glioblastoma by sponging miR-331-3p.

OBJECTIVE: Recent evidence shows that gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) acts as a critical role in the proliferation and metastasis in several tumors. We aimed to explore the expression pattern, function, and potential mechanism of GAPLINC in glioblastoma multiforme (GBM). PATIENTS AND METHODS: The expression levels of GAPLINC and its clinical significance were determined by analyzing TCGA datasets. RT-PCR was performed to detect the levels of GAPLINC and miR-331-3p. CCK-8, colony formation, EdU assays, wound healing assay and transwell invasion assay were performed to analyze the effect of GAPLINC on GBM behaviors. MiRNAs that may interact with GAPLINC were predicted using StarBase and RegRNA 2.0. A luciferase reporter assay was used to detect the targeting effect of GAPLINC on miR-331-3p. RESULTS: We found that GAPLINC expression was significantly up-regulated in both GBM tissues and cell lines. The overexpression of GAPLINC was associated with shorter overall survival and disease-free survival. Functional assays indicated that GAPLINC silencing suppressed GBM cells proliferation, migration, and invasion, and promoted apoptosis. In the mechanism, we found that GAPLINC acted as a competing endogenous RNA to sponge miR-331-3p and knockdown of GAPLINC promoted the expression of miR-331-3p. CONCLUSIONS: Our findings suggested that GAPLINC served as an oncogenic lncRNA in GBM through negative modulation of miR-331-3p, providing a novel treatment targeting for GBM.

Bone mineral density as a dose-response predictor for osteoporosis: a propensity score analysis of longitudinal incident study (KCIS no. 39).

BACKGROUND: Osteoporosis is a global disease burden for aging society. The role of quantitative ultrasound (QUS) in the prediction for osteoporosis in a dose-response manner is hardly addressed. AIM: We aimed to show the dose-response of QUS measurement in the prediction for osteoporosis by a community-based study. DESIGN: A prospective cohort study. METHODS: Participants were recruited between 2000 and 2004. Demographic data and heel QUS measurement were collected at baseline. Diagnosis of osteoporosis was ascertained by the follow-up of this cohort over time. In order to reduce the imbalance of baseline characteristics in the observational study, we applied propensity score by using proportional odds regression analysis to match the quintiles of QUS T-score. RESULTS: A total of 44 957 subjects composed of 17 678 men (39.3%) and 27 279 women (69.7%) were recruited. After adjustments for propensity score, an increase in one unit of QUB T-score led to 7% reduction in the risk for osteoporosis [adjusted odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.89-0.96, P < 0.0001]. Higher quintile of QUS T-score yielded a lower risk of osteoporosis with a gradient relationship [OR: 0.82 (95%CI: 0.72-0.92); OR: 0.81 (95%CI: 0.71-0.91); OR: 0.77 (95%CI: 0.68-0.87) and OR: 0.76 (95%CI: 0.67-0.86)] from the second to highest quintile opposed to first quintile (P < 0.0001). The cumulative incidence of osteoporosis was higher in the lower quintile during follow-up (log-rank test, P < 0.001). CONCLUSION: QUS is an independent predictor for osteoporosis in a dose-response manner using a large population-based cohort. Due to the lower cost and portability of QUS measurement, the pre-screening for osteoporosis by QUS can be considered in the area with limited resources can be a feasible and alternative method.

Cyclotrimerization of phenylacetylene catalyzed by a cobalt half-sandwich complex embedded in an engineered variant of transmembrane protein FhuA.

An (η5-cyclopentadienyl)cobalt(i) complex was covalently incorporated into an engineered variant of the transmembrane protein ferric hydroxamate uptake protein component: A, FhuA ΔCVFtev, using a thiol-ene reaction. A CD spectrum shows the structural integrity of the biohybrid catalyst. MALDI-TOF of the segment containing the anchoring site for the cobalt complex Cys545 confirmed successful conjugation. This biohybrid catalyst catalyzed the cyclotrimerization of phenylacetylene to give a mixture of regioisomeric 1,2,4- and 1,3,5-triphenylbenzene in aqueous medium.

Effect of light deprivation on expression of extended vascular endothelial growth factor and neovascularization in retina of neonatal rats.

OBJECTIVE: The aim of this study is to analyze the effect of light deprivation on the expression of vascular endothelial growth factor (VEGF) and neovascularization in the retina of neonatal rats. MATERIALS AND METHODS: Thirty-six neonatal SD rats (male and female) were used in this study. These rats were numbered randomly and assigned into 3 groups (12 rats in each group), ie. 10-day group (routine feeding after birth, eyeball enucleation on 10th day), 14-day group (routine feeding after birth, eyeball enucleation on 14th day) and light deprivation group (routine feeding within 1st week after birth, feeding with light deprivation within 2nd week after birth, eyeball enucleation on 14th day). The expression level of VEGF mRNA was measured by RT-PCR, and the percentage of the retinal vascular area was calculated by PAS staining, and the number of vascular endothelial cells was counted with a microscope in a double-blind manner. RESULTS: It was found that the expression levels of VEGF mRNA and the number of vascular endothelial cells in 10-day group and light deprivation group were significantly higher than 14-day group (p < 0.05), while the difference between the 10-day group and light deprivation group was not significant. The percentage of retinal vascular area in the 10-day group and light deprivation group was significantly lower than 14-day group (p < 0.05), while the difference between the 10-day group and the light deprivation group was not significant. CONCLUSIONS: The light deprivation delayed the growth of neovessels in the retina.

Effects of risk factors on periodontal disease defined by calibrated community periodontal index and loss of attachment scores.

OBJECTIVES: We evaluated whether and how the effects of risk factors on periodontal disease (PD) were modified by measurement errors using community periodontal index (CPI) and loss attachment (LA) in the community-based survey. METHODS: A pilot validation study was performed to estimate the rates of false negative and false positive for both CPI and LA in 31 subjects from different regions using measurements from 12 well-trained dentists and a senior periodontist as a gold standard. Afterward, a Taiwanese nationwide survey was conducted by enrolling 3,860 participants to estimate the effect of each risk factor on PD calibrated with both sensitivity and specificity of two indices. RESULTS: The values obtained for the sensitivity to false-positive ratio for CPI ranged widely from 1.12 to 7.71, indicating regional variation in both errors. The calibrated adjusted odds ratio for smoking vs non-smoking was higher than the uncalibrated odds ratio for PD defined by CPI (2.75 (2.01, 3.77) vs 2.02 (1.63, 2.52)) and LA (3.85 (2.44, 6.13) vs 1.93 (1.47, 2.54)) scores. Similar underestimation was noted for other risk factors. CONCLUSION: The effects of risk factors on PD measured using CPI and LA in a large population-based survey were underestimated without correcting for measurement errors.

MiR-155 regulates oral squamous cell carcinoma Tca8113 cell proliferation, cycle, and apoptosis via regulating p27Kip1.

OBJECTIVE: P27Kip1 is the one of the negative regulators of the cell cycle that plays an important role in regulating cell cycle and inhibiting cell proliferation by restraining cell in G1 phase. P27Kip1 downregulation maybe related to the occurrence of oral squamous cell carcinoma (OSCC). It was found that miR-155 significantly upregulated in OSCC tissue. Bioinformatics analysis revealed that miR-155 may bind with the 3'-UTR of p27Kip1. This study investigated the role of miR-155 in regulating p27Kip1 and affecting Tca8113 cell proliferation, cycle, and apoptosis. PATIENTS AND METHODS: A total of 46 cases of OSCC patients received treatment in our hospital were enrolled to obtain tumor tissue. Another 25 normal oral mucosa samples were selected as control to detect the relationship between miR-155 and p27Kip1 expressions. Dual luciferase assay was adopted to confirm the targeted relationship between miR-155 and p27Kip1. Flow cytometry was applied to test cell apoptosis and cell cycle. CCK-8 assay was used to evaluate cell proliferation. Caspase-3 activity was detected by spectrophotometry. RESULTS: MiR-155 upregulated, while p27Kip1 declined in OSCC tissue compared with normal oral mucosa. Their expressions were related to TNM stage. MiR-155 targeted suppressed p27Kip1 expression. MiR-155 mimic and/or pEGFP-p27Kip1 transfection obviously declined p27Kip1 expression, blocked cell cycle in G1 phase, reduced cell proliferation, enhanced Caspase-3 activity, and increased cell apoptosis in Tca8113 cells. CONCLUSIONS: MiR-155 increased, while p27Kip1 reduced in OSCC tissue. Inhibition of miR-155 upregulated p27Kip1 expression, blocked cell cycle in G1 phase, weakened cell proliferation, and induced cell apoptosis.

B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics / Péptido natriurético de tipo B e insuficiencia cardiaca aguda: homeostasis de fluidos, biomarcadores y terapéutica

Natriuretic peptides are a family of peptides with similar structures, but are genetically distinct with diverse actions in cardiovascular, renal and fluid homeostasis. The family consists of an atrial natriuretic peptide (ANP) and a brain natriuretic peptide (BNP) of myocardial cell origin, a C-type natriuretic peptide (CNP) of endothelial origin, and a urodilatin (Uro) which is processed from a prohormone ANP in the kidney. Nesiritide, a human recombinant BNP, was approved by the Federal Drug Administration (FDA) for the management of acute heart failure (AHF) in 2001. Human recombinant ANP (Carperitide) was approved for the same clinical indication in Japan in 1995, and human recombinant Urodilatin (Ularitide) is currently undergoing phase III clinical trial (TRUE AHF). This review will provide an update on important issues regarding the role of BNP in fluid hemostasis as a biomarker and therapeutics in AHF (AU)

Los péptidos natriuréticos son una familia de péptidos con estructura semejante, pero distintos genéticamente, con múltiples acciones en la homeostasis cardiovascular, renal y de fluidos. Esta familia está formada por un péptido natriurético auricular y un péptido natriurético cerebral que se originan en las células miocárdicas, un péptido natriurético de tipo C de origen endotelial y una urodilatina que se procesa de una prohormona del péptido natriurético auricular en el riñón. La nesitirida, un péptido natriurético cerebral recombinante humano, fue aprobada por la Administración de Medicamentos y Alimentos (FDA) en el año 2001 para el tratamiento de la insuficiencia cardiaca aguda. El péptido natriurético auricular recombinante humano (carperitida) fue aprobado con las mismas indicaciones clínicas en Japón en el año 1995, y la urodilatina recombinante humana (ularitida) forma parte ahora mismo de un ensayo de fase iii (TRUE-AHF). Esta revisión permitirá actualizar aspectos importantes relativos al papel que desempeña el péptido natriurético cerebral en la homeostasis de fluidos como biomarcador y fármaco para las insuficiencias cardiacas agudas (AU)

Effects of light on the development of melanoposin containing retinal ganglion cells in rats.

OBJECTIVE: The present study was planned to evaluate the effect of light on the development of light-sensitive retinal ganglion cells. MATERIALS AND METHODS: The Sprague-Dawley (SD) rats were segregated into 3 groups (n=18) which included routine feeding 10-day group 1, routine feeding 14-day group 2 and light-deprivation feeding 14-day group 3. The group 1 animals were routinely fed for 10 days in normal light conditions and were sacrificed for analyses on day 10. Similarly, group 2 animals were routinely fed for 14 days in normal light conditions and were sacrificed for analyses on day 14. The group 3 animals were kept were routinely fed for 7 days which was followed by their feeding in a light-deprived conditions and were sacrificed on day 14. RESULTS: The expression of the opsin gene determined by real-time PCR in retinal tissues showed a significant decline in the light-deprived group 3 when compared to other two groups. Furthermore, the melanopsin protein also showed a significant decline in its protein expression in light-deprived group 3 as observed by immune-blot analyses. The immuno-fluorescence analyses also showed the similar trend confirming the effect of light on the development of retinal ganglion cells. CONCLUSIONS: Light is essential for the proper development process of retinal ganglion cells as light directly affects regulatory opsin gene expression.

Impact of mTOR Inhibitors on Cancer Development in Kidney Transplantation Recipients: A Population-Based Study.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. METHODS: We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. RESULTS: During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46-1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33-1.46; P = .34). CONCLUSIONS: The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients.