Self-therapeutic metal-based nanoparticles for treating inflammatory diseases

Inflammatory diseases are key contributors to high mortality globally and adversely affect the quality of life. Current treatments include corticosteroids or nonsteroidal anti-inflammatories that may cause systemic toxicity and biologics that may increase the risk of infection. Composite nanoparticles that bear not only the drug payload but also targeting ligands for delivery to inflammation sites at lowered systemic toxicity are established in the nanomedicine field, but their relatively large size often leads to systemic clearance. Metal-based nanoparticles with intrinsic anti-inflammatory properties represent attractive alternatives. They are not only designed to be compact for crossing biological barriers (with the nanoparticle serving as a dual carrier and drug), but also support label-free tracking of their interactions with cells. The review commences with an outline of the common inflammatory diseases, inflammatory pathways involved, and conventional drug-loaded nanoparticles for anti-inflammation. Next, the review features the emerging applications of self-therapeutic metal-based nanoparticles (e.g., gold, coper oxide, platinum, ceria, and zinc oxide) for managing inflammatory diseases in animals over the past three years, focusing on therapeutic outcomes and anti-inflammatory mechanisms. The review concludes with an outlook on the biodistribution, long-term toxicity, and clinical translation of self-therapeutic metal-based nanoparticles.

Identification of AIPL1 gene variants in two Chinese families with Cone-rod dystrophy / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic gene variants in two Chinese families with cone-rod dystrophy(CORD).@*METHODS@#After the informed consent and comprehensive ophthalmic examinations for the patients, 3 mL peripheral blood was taken from the patients' blood vessel and DNA was extracted. The DNA was sequenced by whole-exome sequencing technology and variants were analyzed.@*RESULTS@#Two novel compound heterozygous AIPL1 variants were detected in two patients, which were c.923T to C (p.L308P) and c.421C to T (p.Q141X) variants in Family 1, c.572T to C (p.L191P) and c.421C to T (p.Q141X) in Family 2.@*CONCLUSION@#The results supported that AIPL1 gene variants are the main cause of the two CORD families. Whole-exome sequencing technology is a useful tool in the clinical differentiated diagnosis and genetic counseling for CORD patients.

Identification of AIPL1 gene variants in two Chinese families with Cone-rod dystrophy / 中华医学遗传学杂志

Objective@#To detect pathogenic gene variants in two Chinese families with cone-rod dystrophy(CORD).@*Methods@#After the informed consent and comprehensive ophthalmic examinations for the patients, 3 mL peripheral blood was taken from the patients’ blood vessel and DNA was extracted. The DNA was sequenced by whole-exome sequencing technology and variants were analyzed.@*Results@#Two novel compound heterozygous AIPL1 variants were detected in two patients, which were c. 923T>C(p.L308P) and c. 421C>T(p.Q141X) variants in Family 1, c. 572T>C(p.L191P) and c. 421C>T(p.Q141X) in Family 2 .@*Conclusion@#The results supported that AIPL1 gene variants are the main cause of the two CORD families. Whole-exome sequencing technology is a useful tool in the clinical differentiated diagnosis and genetic counseling for CORD patients.

Clinical features and identification of gene mutation in families with familial exudative vitreoretinopathy / 中华眼底病杂志

Objective To identify mutations in NDP,FZD4,LRPS,TSPAN12 in Chinese families with familial exudative vitreoretinopathy (FEVR) and observe the clinical features.Methods Retrospective case series study.The 9 patients (18 eyes) and 5 normal members from 4 unrelated families were included in the study.The patients medical history and family history were collected in detail.All patients underwent best corrected visual acuity (BCVA),slit-lamp biomicroscopy,fundus colorized photography,fundus fluorescein angiography (FFA).Genomic DNA were collected from all the patients.Mutations were detected by directly sequencing to the whole coding region and exon-intron boundaries ofNDP,FZD4,LRP5 and TSPAN12 gene.Polyphen and SWT programs were used to predict the effects on the structure and functional properties of mutant protein.Results There were two affected individuals in the family 2 carried LRP5 gene mutation [c.1330C＞T (p.R444C)] in exon 6 by sequence analysis.A score of 0.882 was acquired by Polyphen program analysis.And the missense change was predicted to be pathogenic by SIFT.Fundus changes of the proband showed angioplasia,tortuosity of peripheral vessels.And temporal dragging of the optic disc,peripheral avascular zone,neovascularization were found in FFA.Brush-like and straight of peripheral vessels were found in I 1.No variant was found in NDP,FZD4 and TSPAN12 gene.Conclusion Our study supports the gene mutation c.1330C＞T (p.R444C) of LRP5 is pathogenesis of FEVR.Patients with the same mutation could have variable phenotypic characteristics.

Screening of TYR gene mutations and clinical classification in oculocutaneous albinism patients / 中华实验眼科杂志

Background Oculocutaneous albinism (OCA) is a hereditary disease of pigment absence in eyes,skin and hair due to the lack of congenital melanocyte.OCA is classified into 7 types based on different genetic mutations,and the mutation of tyrosinase (TYR) gene causes OCA type 1 (OCA1).OCA has obvious genetic heterogeneity and phenotypic heterogeneity.The molecular diagnosis of the mutant gene is helpful for the classification and molecular pathogenesis study of OCA.Objective This study was to screen the TYR mutation in OCA patients,and to analyze the association between the gene mutation type and clinical phenotype.Methods Ten patients with OCA were enrolled in Tianjin Ophthalmological Hospital from January 2011 to December 2014.The clinical and ocular manifestations of the patients were examined.Peripheral venous blood 3 ml was collected in the patients and their lineal relatives for the extraction of genomic DNA.Extracted DNA was amplified by PCR and the TYR gene sequence was analyzed,including all 5 exon coding sequence and exon 5 ' and 3' end and the non-coding region sequence of intron splicing in TYR gene.This study complied with Helsinki Declaration and the protocol was approved by Ethic Committee of Tianjin Eye Hospital.Informed consent was obtained from each subject.Results All the patients showed white or reddish hair and snow-white skin,and different degrees of pigment lack was seen in iris.The best corrected visual acuity of the patients was 0.05-0.2,and 3 patients complicated with nystagmus.Fundus findings showed a sunset-like change and dysplasia of macula.The TYR gene sequencing revealed that patient 1 was OCA1A subtype,with the compound heterozygous mutant of c.832C＞T (p.R278X) and c.1217C＞T (p.P406L),and his/her parents occurred the heterozygous mutation of exons P406L and R278X.The phenotype of the patient 1 was white hair and white iris.The patient 3 was OCA1B subtype,with the compound heterozygous mutations of c.1265G＞A (p.R422Q) and c.1217C＞T (p.P406L),showing an appearance of reddish brown hair and sallow iris.TYR gene mutant was not detected in other 8 patients.Conclusions The mutation of TYR gene is the main cause of OCA1 type.The phenotype of OCA1A subtype is no pigment in eyes and hair,and one of OCA1B subtype was obviously lessening of pigment.The difference of mutant genes of OCA is the cause of genetic and phenotypic heterogeneity.

Mutation analysis of Pax6 in Chinese patients with congenital aniridia / 中华实验眼科杂志

Background Congenital aniridia is a rare congenital autosomal dominant disease,which is shown as aniridia of double eyes,and the paired box gene 6 (Pax6) gene mutation is now known to be associated with congenital aniridia.Objective This study was to screen the Pax6 gene mutation in patients with congenital aniridia.Methods Eleven patients with congenital aniridia were enrolled in Tianjin Eye Hospital from August 2012 to October 2015,including 6 patients from 3 congenital aniridia family and 5 sporadic patients.All patients received routine ophthalmic examination.Peripheral venous blood of 3 ml was collected from the patients for DNA extraction according to the standard process of DNA isolation instructions,and all the exons of Pax6 gene,Elp4 gene,exon 5 ' and 3',intron splice sequence and SIMO sequence were amplified by PCR.Pax6 genes of the patients were sequenced using Sanger direct sequencing and multiplex ligation dependent probe amplification (MLPA) and compared with those of 500 ocular trauma patients.This study complied with Helsinki declaration,and written informed consent was obtained from each patient prior to any medical examination.Results Iris absence was found in all the patients,and the visions acuity was hand motion to 0.2.Lens dislocation was seen in 1 patient.Direct sequencing results found that three patients in AN-O1 family were c.688g＞t (p.E230X) mutation of Pax6 gene,and 3 of 5 sporadic patients carried c.468g＞a (p.W156X),c.613c＞t (p.Q205X) and c.141 +2t＞c mutant of Pax6 gene,and the c.688g＞t (pE230X) mutation was a novel-discovered mutation.No any mutation in Pax6,Elp4 gene and SIMO fragment was detected in 1 patient from AN-02 family,2 patients from AN-03 family and 2 sporadic patients by both direct sequencing and MLPA validation.No above-mentioned mutation was found in 500 normal individuals.Conclusions The mutation of Pax6 gene is a pathogenic mutation in congenital aniridia patients,and c.688g＞t (p.E230X) is a novel Pax6 mutant,which expanded the mutation spectrum of Pax6 gene.

Recent advance about cytokines of proliferative vitreoretinopathy / 中华实验眼科杂志

Proliferative vitreoretinopathy (PVR) is a leading cause of blindness and caused by abnormal repairs for the damaged vitreous and retina.The formation of PVR involves many cytokines,including platelet derived growth factor (PDGF),vascular endothelial growth factor,hepatocyte growth factor,transforming growth factor-β,epidermal growth factor,tumor necrosis factor-α,connective tissue growth factor,etc.The Jagged-1/Notch signaling pathway and RhoA/ROCK signaling pathway are involved in the epithelial-mesenchymal transition of retinal pigment epithelium (RPE) cells.The migration and proliferation of RPE cells are associated with the PKC/ERK and Akt/mTORCl signaling pathway.Non-PDGF cytokines indirectly active PDGF receptor α,which seems to be the key pathway in the development of PVR.The methods of cocktail neutralizing reagents targeted to multiple cytokines and the antioxidant N-acetylcysteine are effective in preventing PVR.Here,we reviewed the mechanisms and signaling pathways of multiple relevant cytokines involved in development and treatment of PVR.