Biosynthesis of selenium nanoparticles and their protective, antioxidative effects in streptozotocin induced diabetic rats.

Green synthesis of selenium nanoparticles (Se NPs) was performed by mixing Hibiscus sabdariffa (roselle plant) leaf extract with the solution of selenious acid (H2SeO3) under continuous stirring conditions resulting the roselle plant secondary metabolites conjugated Se NPs. The existence of functional groups of roselle plant secondary metabolites on the surface of prepared Se NPs was confirmed by Fourier transform infrared spectroscopy (FTIR). The formation of crystalline nanoparticles with anisotropic shape was confirmed by transmission electron microscopy (TEM) images. Furthermore, we also studied anti-oxidative and protective effects of Se NPs in streptozotocin (STZ) induced diabetes rats. These STZ induced diabetic rats were daily exposed to Se NPs or/and insulin treatment and the effect of Se NPs on the factors correlated to oxidative damage in the rat testes were evaluated. The biochemical studies showed that the Se NPs are capable to enhance the serum testosterone reduction caused due to STZ induced diabetes. In addition, Se NPs can significantly reduce the oxidative stress indicators of the testicular tissue such as nitric oxide and lipid peroxidation. However, the treatment of Se NPs on the STZ induced diabetic rats increased the activities of antioxidant enzyme as well as the glutathione content in testicular tissues. Furthermore, microscopic studies revealed that the Se NPs are capable of preventing the histological damage in the testes of STZ induced diabetic rats. Altogether, these results explained the possible effects of Se NPs in attenuating oxidative damage induced by diabetes, especially in the testicular tissue.

Effect of hyperlipidemia on the incidence of cardio-cerebrovascular events in patients with type 2 diabetes.

BACKGROUND: This study was to explore the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. METHODS: Three hundred ninety five patients with type 2 diabetes in our hospital from January 2012 to January 2016 were followed up with an average of 3.8 years. The incidence of cardio-cerebrovascular diseases between diabetes combined with hyperlipidemia group (195 patients) and diabetes group (200 patients) were made a comparison. Multivariable Cox's proportional hazards regression model was used to analyze the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. RESULTS: Diastolic blood pressure, systolic blood pressure, high-density lipoprotein, low-density lipoprotein, body mass index and hyper-sensitive C-reactive protein were higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). At the end of the follow-up period, all-cause mortality, cardio-cerebrovascular diseases mortality, and the incidence of myocardial infarction, cerebral infarction, cerebral hemorrhage and total cardiovascular events were significantly higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). The analysis results of multivariable Cox's proportional hazards regression model showed that the risks of myocardial infarction and total cardiovascular events in diabetes combined with hyperlipidemia group were respectively 1.54 times (95%CI 1.13-2.07) and 1.68 times (95%CI 1.23-2.24) higher than those in diabetes group. Population attributable risk percent of all-cause mortality and total cardiovascular events in patients with type 2 diabetes combined with hyperlipidemia was 9.6% and 26.8%, respectively. CONCLUSIONS: Hyperlipidemia may promote vascular endothelial injury, increasing the risk of cardio-cerebrovascular diseases in patients with type 2 diabetes. Medical staffs should pay attention to the control of blood lipids in patients with type 2 diabetes to delay the occurrence of cardio-cerebrovascular diseases.

Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a rare X-linked recessive inherited disease that is considered a major cause of steroidogenesis disorder and is associated with variants or complete deletion of the NR0B1 gene. The DAX-1 protein (encoded by NR0B1) is a vertebrate-specific orphan nuclear receptor and is also a transcriptional factor for adrenal and reproductive development. CAH usually causes adrenal insufficiency in infancy and early childhood, leading to hypogonadotropic hypogonadism in adulthood; however, few adult cases have been reported to date. In this study, we examined a Chinese family with one adult patient with CAH, and identified a putative variant of NR0B1 gene via next-generation sequencing (NGS), which was confirmed with Sanger sequencing. A novel nonsense variant (c.265C>T) was identified in the NR0B1 gene, which caused the premature termination of DAX-1 at residue 89 (p.G89*). Furthermore, mutant NR0B1 gene displayed a partial DAX-1 function, which may explain the late pathogenesis in our case. Additionally, qPCR revealed the abnormal expression of four important genes identified from ChIP-seq, which were associated with energy homeostasis and steroidogenesis, and were influenced by the DAX-1 mutant. In addition, hormone disorders can be caused by DAX-1 mutant and partially recovered by siRNA of PPARGC1A. Herein, we identified a novel nonsense variant (c.265C>T) of NR0B1 in a 24-year-old Chinese male who was suffering from CAH. This mutant DAX-1 protein was found to have disordered energy homeostasis and steroidogenesis based on in vitro studies, which was clinically consistent with the patient's phenotypic features.

GJA8 missense mutation disrupts hemichannels and induces cell apoptosis in human lens epithelial cells.

Autosomal dominant congenital cataract (ADCC), the most common hereditary disease, is a major cause of eye disease in children. Due to its high genetic and clinical heterogeneity, the identification of ADCC-associated gene mutations is essential for the development of molecular therapies. In this study, we examined a four-generation Chinese pedigree with ADCC and identified putative mutations in ADCC candidate genes via next-generation sequencing (NGS) followed by Sanger sequencing. A novel missense mutation in GJA8 (c.T217C) in ADCC patients causes a serine-to-proline substitution at residue 73 of connexin 50 (Cx50); no mutation was found in unaffected family members and unrelated healthy individuals. Functional analysis revealed that this missense mutation disrupts protein function in human lens epithelial cells (HLEpiCs), which fails to form calcium-sensitive hemichannels. Furthermore, mutant Cx50 leads to decreased ROS scavenging by inhibiting G6PD expression and thus induces cell apoptosis via aberrant activation of the unfolded protein response (UPR). In conclusion, we report a novel GJA8 heterozygous mutation in a Chinese family with a vital role in ADCC, broadening the genetic spectrum of this disease.

Surgical treatment and visual outcomes of cataract with persistent hyperplastic primary vitreous.

AIM: To evaluate the surgical treatment and visual outcomes of eyes with cataract and persistent hyperplastic primary vitreous (PHPV). METHODS: This retrospective study included patients with cataract and PHPV treated with various strategies. Anterior PHPV was treated using phacoemulsification with underwater electric coagulation on posterior capsule neovascularization, posterior capsulotomy, anterior vitrectomy, and intraocular lens (IOL) implantation. Posterior PHPV was treated with lensectomy, posterior vitrectomy, retinal photocoagulation, and IOL implantation or silicone oil tamponade. Visual acuity (VA), pattern visual evoked potential (P-VEP), anatomic recovery, postoperative complications, and amblyopia outcome were examined. Subjects were followed-up for 3-48mo after surgery. RESULTS: Of the 30 patients (33 eyes) with congenital cataract and PHPV included (average age, 39.30±35.47mo), 9 eyes had anterior PHPV and 24 had posterior PHPV. Thirty-two eyes were surgically treated. Eyes with anterior PHPV received an IOL during one-stage (6 eyes) and two-stage (3 eyes) implantation. Postoperative complications included retinal detachment (1 eye) and recurrent anterior chamber hemorrhage (1 eye). In eyes with posterior PHPV, 6 and 11 eyes received IOLs in one- and two-stage procedures, respectively. Silicone oil was retained in 2 eyes, and IOLs were not implanted in 4 eyes. VA significantly improved in 25 eyes following operations and 3-48mo of amblyopia treatment. P-VEP P100 was improved following surgery in both PHPV types. CONCLUSION: Our surgical strategies are appropriate and effective for anterior and posterior PHPV. Early surgical intervention and amblyopia therapy result in positive treatment outcomes.

Two novel mutations identified in ADCC families impair crystallin protein distribution and induce apoptosis in human lens epithelial cells.

Congenital cataract (CC) is a clinical and genetically heterogeneous eye disease that primarily causes lens disorder and even amblyopic blindness in children. As the mechanism underlying CC is genetically inherited, identification of CC-associated gene mutations and their role in protein distribution are topics of both pharmacological and biological research. Through physical and ophthalmic examinations, two Chinese pedigrees with autosomal dominant congenital cataract (ADCC) were recruited for this study. Mutation analyses of CC candidate genes by next-generation sequencing (NGS) and Sanger sequencing revealed a novel missense mutation in CRYBB2 (p.V146L) and a deletion mutation in CRYAA (p.116_118del). Both mutations fully co-segregated were not observed in unaffected family members or in 100 unrelated healthy controls. The CRYBB2 missense mutation disrupts the distribution of CRYBB2 in human lens epithelial cells (HLEpiCs), and the CRYAA deletion mutation causes hyperdispersion of CRYAA. Furthermore, these two crystallin mutations result in aberrant expression of unfolded protein response (UPR) marker genes as well as apoptosis in HLEpiCs. Collectively, these findings broaden the genetic spectrum of ADCC.