Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events: a narrative review.

Multiple evanescent white dot syndrome (MEWDS) is a rare fundus disease, characterized by acute vision loss and visual field defects. Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS. However, as the number of reported cases increases, secondary MEWDS occurs in other related retinal diseases and injuries, exhibiting some special characteristics. The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy (MFC/PIC), acute zonal occult outer retinopathy, best vitelliform macular dystrophy, pseudoxanthoma elasticum, and ocular toxoplasmosis. The related retinal injury is laser photocoagulation, surgery, and trauma. Although primary MEWDS often have a self-limiting course, secondary MEWDS may require treatment in some cases, according to the severity of concomitant diseases and complications. Notably, MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation, needs positive treatment with corticosteroids. The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch's membrane. The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances. Its prognosis and treatment depend on the severity of complications. Current studies propose that the etiology is associated with immune factors, including viral infection, inflammation in choroid and Bruch's membrane, and antigen exposure caused by retinal and/or choroidal insults. More pathogenic studies should be conducted in the future. Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.

The multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy lesion with multiple evanescent white dot syndrome-like features: a retrospective study.

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS)-like features is a rare condition triggered by a macular disease or iatrogenic injury, exhibiting MEWDS changes in the fundus. This study aims to describe the multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) lesions with MEWDS-like features. METHODS: Six cases were studied retrospectively. All cases were given regional and oral corticosteroids. RESULTS: All cases showed an isolated juxtafoveal yellowish-white MFC/PIC lesion with disruption of RPE-Bruch's membrane-choriocapillaris complex (RPE-BM-CC), subretinal hyperreflective materials and choroidal thickening on optical coherence tomography. Two weeks after presentation, the grayish-white dots disappeared spontaneously and the corticosteroids were given. After four weeks, the ellipsoid zone (EZ) around the lesion and hyper-autofluorescence resolved. After 13 weeks, five cases showed shrinkage of the juxtafoveal lesion and restoration of foveal EZ. After six months, the juxtafoveal lesion became pigmented. Only one case developed type 2 choroidal neovascularization. CONCLUSIONS: The clinical course of MEWDS-like manifestations is still evanescent in our cases. The yellowish-white juxtafoveal MFC/PIC lesions with disruption of RPE-BM-CC and choroidal thickening showed a well-controlled prognosis after corticosteroid treatment.

Heat shock protein HSPA13 promotes hepatocellular carcinoma progression by stabilizing TANK.

HSPA13, an important member of the heat shock protein family, plays an essential role in the oncogenesis of many organs, but the mechanism and function in hepatocellular carcinoma (HCC) is still unclear. In the present study, we found that HSPA13 was highly expressed in HCC and predicted poor clinical prognosis. Upregulation of HSPA13 was significantly associated with vascular invasion in HCC patients. Functionally, knockdown experiments demonstrated that HSPA13 promoted HCC proliferation, migration, and invasion. Mechanistic investigation showed that HSPA13 could interact with TANK to inhibit its ubiquitination and degradation. In addition, the expression of HSPA13 and TANK were positively correlated in HCC tissues. To conclude, the present study uncovers the oncogenic function of HSPA13 in the progression of HCC by regulating the stability of TANK. These findings suggest that HSPA13 and TANK may serve as promising targets for the diagnosis and treatment of HCC.

Case report: A frameshift mutation in CLCN2-related leukoencephalopathy and retinopathy.

Background: Leukoencephalopathy and visual impairment have been linked to loss-of-function mutations in the CLCN2 gene (MIM #600570). However, the ocular features caused by the CLCN2 mutations remain poorly understood and seldom reported. This study aims to present a novel mutation and characterize the ocular phenotype in a Chinese female diagnosed with CLCN2-related leukoencephalopathy (CC2L), also known as leukoencephalopathy with ataxia (LKPAT; MIM #615651). Case presentation: A 20-year-old Chinese female presented with bilateral blurred vision persisting for 2 years, which had worsened over the past 6 months. Ophthalmologic examination revealed bilateral post-capsular cataracts, macular retinal atrophy, and peripheral retinal pigmentation. Swept-source optical coherence tomography (SS-OCT) showed bilateral choroidal capillary atrophy, loss of the outer retinal layer, and a novel noteworthy sign of vacuole-like vitreoretinopathy. Cranial magnetic resonance imaging confirmed leukoencephalopathy. Genetic testing identified a novel homozygous pathogenic c.1382_1386del (p.P461Lfs*13) mutation in exon 13 of the CLCN2 gene. Conclusion: This case report expands the knowledge of CLCN2 mutations and their associated ocular manifestations in patients with CC2L. The identified ophthalmic features may serve as crucial indicators for early diagnosis in individuals with CC2L, especially in the absence of evident neurological symptoms.

Case report: A rare appearance of preretinal deposits in a patient with uveitis: multimodal imaging observation.

Background: Uveitis is a disease presenting with varied clinical symptoms and potentially devastates visual function. Here, we report a patient with uveitis exhibiting a rare appearance of preretinal deposits (PDs). Case presentation: A 49-year-old female showed vitreous opacity and perivascular white PDs involving veins and arteries. The interferon-gamma release assay was strongly positive and chest computed tomography showed signs of calcified nodules; other tests were unremarkable. The patient was diagnosed with uveitis and tubercular infection. The patient was given systemic anti-tubercular therapy and steroids, which were subsequently combined with immunosuppressants. The shrinkage of HRD was more sensitively observed with OCT than on photographs during follow-up visits. The right eye was relieved subsequently, but the left eye showed vitreous opacity and responded poorly to the treatment. Three months after the dexamethasone intravitreal implant, the perivascular deposits in the left eye disappeared and the vitreous opacity was relieved. Conclusion: PDs can appear as spotted deposits in the posterior pole and segmental deposits in the periphery in patients with uveitis, which mainly involves the vitreous cavity and is easily confused with retinal vasculitis. OCT can more sensitively observe the response than other examinations.

Upregulation of helicase-like transcription factor predicts poor prognosis and facilitates hepatocellular carcinoma progression.

Helicase-like transcription factor (HLTF) belongs to the family of SWI/SNF proteins, which has been reported to exert oncogenic function in several human cancers. However, to date, its functional role in hepatocellular carcinoma (HCC) has not been revealed. Here, we found that HLTF was highly expressed in HCC tissues compared to nontumor tissues. Additionally, upregulation of HLTF was significantly associated with poor prognosis of patients with HCC. Functional experiments demonstrated that knockdown of HLTF expression significantly inhibited the proliferation, migration, and invasion of HCC cells in vitro, and suppressed tumor growth in vivo. In conclusion, our results suggest that upregulation of HLTF is associated with the development of HCC, and HLTF may be a potential therapeutic target for HCC treatment.

Metformin synergistically enhances the antitumour activity of Lenvatinib in hepatocellular carcinoma by altering AKT-FOXO3 signalling pathway.

BACKGROUND AND AIMS: Lenvatinib is a first-line drug commonly used in the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is very limited due to drug resistance. Therefore, there is a great need to explore its combination with other agents to achieve better therapeutic effects. Metformin has been demonstrated to show an anti-cancer effect. This study aimed to investigate the combined effect of lenvatinib with metformin in HCC cells both in vitro and in vivo and elucidate the possible molecular mechanisms. METHODS: Flow cytometry, colony formation, CCK-8 and transwell assays were used to study the effect of Lenvatinib-Metformin combination on the malignant behaviour of HCC cells in vitro. Constructing an animal model of tumour-bearing to study the effect of combined drugs on HCC in vivo. Western blot experiments were performed to assess the relationship between AKT and FOXO3 and the cellular translocation of FOXO3. RESULTS: Our results suggested that Lenvatinib and Metformin synergistically inhibited HCC growth and motility. Mechanistically, the combination of Lenvatinib and Metformin synergistically suppressed the activation of the AKT signalling pathway, which in turn reduced the phosphorylation level of downstream effector FOXO3 and induced its nuclear aggregation. In vivo studies further confirmed the synergistic suppression of lenvatinib with metformin in HCC growth. CONCLUSION: The Lenvatinib-Metformin combination may provide a potential therapeutic strategy to improve the prognosis of HCC patients.

Clinical Features and Possible Origin of Preretinal Deposits in Different Ocular Diseases and Events: A Narrative Review.

Preretinal deposits (PDs) are a rare condition among fundus diseases. We found that preretinal deposits have some features in common that can provide clinical information. This review affords an overview of PDs in different but related ocular diseases and events, and summarizes the clinical features and possible origin of PDs in related conditions, providing diagnostic clues for ophthalmologists when facing PDs. A literature search was performed using three major electronic databases (PubMed, EMBASE, and Google Scholar) to identify potentially relevant articles published on or before June 4, 2022. Most of the cases in the enrolled articles had optical coherence tomography (OCT) images to confirm the preretinal location of the deposits. Thirty-two publications reported PD-related conditions, including ocular toxoplasmosis (OT), syphilitic uveitis, vitreoretinal lymphoma, human T-cell lymphotropic virus type 1 (HTLV-I) associated uveitis or HTLV-I carriers, acute retinal necrosis, endogenous fungal endophthalmitis, idiopathic uveitis, and exogenous materials. Based on our review, OT is the most frequent infectious disease to exhibit PDs, and silicone oil tamponade is the most common exogenous cause of preretinal deposits. PDs in inflammatory diseases are highly suggestive of active infectious disease and are preferentially accompanied by a retinitis area. However, PDs will largely resolve after etiological treatment in either inflammatory or exogenous conditions.

Dissection of the Pearl of Csaba pedigree identifies key genomic segments related to early ripening in grape.

Pearl of Csaba (PC) is a valuable backbone parent for early-ripening grapevine (Vitis vinifera) breeding, from which many excellent early ripening varieties have been bred. However, the genetic basis of the stable inheritance of its early ripening trait remains largely unknown. Here, the pedigree, consisting of 40 varieties derived from PC, was re-sequenced for an average depth of ∼30×. Combined with the resequencing data of 24 other late-ripening varieties, 5,795,881 high-quality single nucleotide polymorphisms (SNPs) were identified following a strict filtering pipeline. The population genetic analysis showed that these varieties could be distinguished clearly, and the pedigree was characterized by lower nucleotide diversity and stronger linkage disequilibrium than the non-pedigree varieties. The conserved haplotypes (CHs) transmitted in the pedigree were obtained via identity-by-descent analysis. Subsequently, the key genomic segments were identified based on the combination analysis of haplotypes, selective signatures, known ripening-related quantitative trait loci (QTLs), and transcriptomic data. The results demonstrated that varieties with a superior haplotype, H1, significantly (one-way ANOVA, P < 0.001) exhibited early grapevine berry development. Further analyses indicated that H1 encompassed VIT_16s0039g00720 encoding a folate/biopterin transporter protein (VvFBT) with a missense mutation. VvFBT was specifically and highly expressed during grapevine berry development, particularly at veraison. Exogenous folate treatment advanced the veraison of "Kyoho". This work uncovered core haplotypes and genomic segments related to the early ripening trait of PC and provided an important reference for the molecular breeding of early-ripening grapevine varieties.

An iris puncture technique for restoration of the anterior chamber in vitrectomy for pediatric vitreoretinopathies.

Purpose: To present a novel usage of iris puncture-assisted lensectomy with anterior vitrectomy or vitrectomy in pediatric patients with the absence of anterior chamber caused by various advanced vitreoretinopathies complicated with capsule-endothelial, iris-endothelial adhesion, and secondary glaucoma. Design: Prospective study. Materials and methods: Forty-one patients were enrolled in this consecutive, prospective study. The iris puncture was performed in all patients using a 20G Vitrectomy Microsurgical Knife, followed by the lensectomy with anterior vitrectomy or vitrectomy. Demographic information, the number of iris puncture times, surgical procedure, intraoperative and postoperative complications, therapy, and prognosis were collected. Patients were followed up for at least 6 months. Results: A total of 18 female patients and 23 male patients were included, with a mean age of 9.5 ± 7.5 months. The formation of anterior chamber formation was achieved in 28 (68.3%) eyes, with only 1 initial episode of iris puncture, 11 (26.8%) patients required 2 episodes, and 3 episodes of iris puncture, with additional external drainage of subretinal fluid, were needed in the remaining 2 (4.9%) patients. Except for iris incarceration, which occurred in 7 (17%) eyes during operation, there was no iridodialysis or subretinal fluid overflow during operation. At the last visit (mean: 12.16 ± 5.38 months of follow-up), all eyes had a reconstructed anterior chamber with normal depth. No synechiae between the iris and the cornea occurred after surgery. The mean postoperative intraocular pressure was 6.23 ± 1.64 mmHg. A hazy cornea vanished in 31 out of 41 (75.6%) eyes, relieved in 8 out of 41 eyes (19.5%), and 2 out of 41 eyes (4.88%) did not change. In the 25 eyes accepting vitrectomy and lensectomy, 20 out of 25 (80%) achieved different degrees of reattachment. Conclusion: The innovative iris puncture technique is effective, simple, and safe management for the anterior chamber disappearance caused by various advanced pediatric vitreoretinopathies, which helped to lower the intraocular pressure and offers a chance for lensectomy with anterior vitrectomy or vitrectomy.

LRP5 BIALLELIC MUTATIONS CAUSE A HIGHER INCIDENCE OF SEVERE PHENOTYPE COMPARED WITH LRP5 MONOALLELIC MUTATION.

PURPOSE: To analyze the clinical features of LRP5 gene mutation-related familial exudative vitreoretinopathy and explore the potential phenotype-genotype correlation on LRP5 gene. METHODS: Eighty-seven familial exudative vitreoretinopathy (FEVR) families with LRP5 mutations were selected from 722 FEVR patients, which were divided into 2 groups, including 22 autosomal-recessive FEVR (ar-FEVR) families and 65 autosomal-dominant FEVR (ad-FEVR) families. Clinical and genetic data were retrospectively analyzed. The potential phenotype-genotype correlation was explored from the mutation type and inheritance pattern. RESULTS: No significant difference between the LRP5 null mutation subgroup and the LRP5 missense mutation subgroup was observed in the proportion of FEVR stage and the ratio of ocular involvement. Instead, a significant difference between the LRP5 ar-FEVR subgroup and the LRP5 ad-FEVR subgroup was observed in the proportion of FEVR stage and the ratio of binocularly severe phenotype. The probands with LRP5 gene recessive mutation showed a higher incidence of severe phenotype. Moreover, the ratio of binocularly severe patients in ar-FEVR was nearly 3.5 times higher than that in ad-FEVR. CONCLUSION: The severity of phenotype was more likely to be related to the synergistic effect of the variants.

Long-term clinical prognosis of 335 infant single-gene positive FEVR cases.

PURPOSE: To describe and analyze the clinical prognosis of infants diagnosed of familial exudative vitreoretinopathy (FEVR) with single gene mutation in long-term follow-up. METHODS: A retrospective case study was conducted on 355 FEVR infants with single positive gene. RESULT: Of the 335 single-gene positive infant FEVR cases (under 3 years old), 20% (n = 67) was diagnosed of strabismus at first visit. Staging of various genotypes was different (P < 0.001). Patients with NDP mutations presented the most severe clinical phenotypes and patients with ZNF408 mutations presented the mildest clinical phenotypes. Most infants underwent surgery under 1 year old (5th stage 75 of 108 [69.44%]). The axial length of different genotypes showed no significant difference (P = 0.2891). The 1st to 3rd stage cases were given intravitreal injection and/or retina photocoagulation with the last follow-up vision above 20/67. The 4th to 5th stage cases received the transcorneal vitrectomy with lensectomy or lens sparing vitrectomy (LSV), whose lens maintained transparent after LSV (11/14[78.58%]). After 2 to 10 years of follow-up, 37.96% (41/108) of post-surgery cases showed retinal funnel-like unfold and posterior pole unfold, 69.57% (16/ 23) of which received second surgery for closure of pupil with good prognosis. At the last follow-up, 20% (60/300) were with vision above 20/200. CONCLUSION: LRP5 gene mutation was the most common mutation in FEVR patients. The severity of the clinical phenotype varied with different gene mutations. The main surgical methods for cases at Stage 4-5 were transcorneal vitrectomy with lensectomy or LSV. The earlier FEVR occurred, the worse prognosis would be. Active surgical intervention and lens sparing were necessary for cases at Stage 4-5.

CLINICAL CHARACTERISTICS OF STREAKY MULTIFOCAL CHOROIDITIS: A Subtype of Multifocal Choroiditis.

PURPOSE: To describe and analyze clinical characteristics of multifocal choroiditis with linear streaks (LSs). METHODS: Eight cases of multifocal choroiditis with LSs were retrospectively studied. Multimodal imaging was performed. Demographic data and spherical equivalent were collected. Axial length was measured. RESULTS: All cases are young myopic women with a mean age of 17.13 ± 3.64 years (range, 13-23 years), presenting with vision loss and distortion. Nine eyes with LSs were high myopia of -8.97 ± 2.69 D (range, -6.00 to 12.5 D; growing by 1.88 ± 0.61 D annually since wearing glasses), with mean axial length of 26.36 ± 1.71 mm. Vitreous cells were noted in seven eyes. LSs were located in the equator (eight eyes), around the optic disk (three eyes), and at the edge of the posterior pole (one eye). Angio-optical coherence tomography showed choroidal neovascularization in eight eyes, especially 2 to 3 choroidal neovascularizations in three eyes. The location of choroidal neovascularization were in subfovea (three eyes), parafovea (six eyes), and perifovea (two eyes). Swept source optical coherence tomography showed punched-out disruption of retinal pigment epithelium‒Bruch's membrane‒choriocapillaris complex at the LSs' sites. LSs showed fluorescence staining on late FA but hypofluorescence throughout all phases on ICGA. CONCLUSION: Multifocal choroiditis with LSs mostly occurs in young women with high myopia, especially occurring in eyes with rapid progression of myopia. LSs are mainly located in the midperiphery near the equator, being prone to concur with choroidal neovascularization. Based on our findings, we propose a new term called "streaky multifocal choroiditis" as a subtype of multifocal choroiditis.

Genome-wide identification and expression analysis of JmjC domain-containing genes in grape under MTA treatment.

Histone demethylases containing the JmjC domain play an extremely important role in maintaining the homeostasis of histone methylation and are closely related to plant growth and development. Currently, the JmjC domain-containing proteins have been reported in many species; however, they have not been systematically studied in grapes. In this paper, 21 VviJMJ gene family members were identified from the whole grape genome, and the VviJMJ genes were classified into five subfamilies: KDM3, KDM4, KDM5, JMJD6, and JMJ-only based on the phylogenetic relationship and structural features of Arabidopsis and grape. After that, the conserved sites of VviJMJ genes were revealed by protein sequence analysis. In addition, chromosomal localization and gene structure analysis revealed the heterogeneous distribution of VviJMJ genes on grape chromosomes and the structural features of VviJMJ genes, respectively. Analysis of promoter cis-acting elements demonstrated numerous hormone, light, and stress response elements in the promoter region of the VviJMJ genes. Subsequently, the grape fruit was treated with MTA (an H3K4 methylation inhibitor), which significantly resulted in the early ripening of grape fruits. The qRT-PCR analysis showed that VviJMJ genes (except VviJMJ13c) had different expression patterns during grape fruit development. The expression of VviJMJ genes in the treatment group was significantly higher than that in the control group. The results indicate that VviJMJ genes are closely related to grape fruit ripening.

Engineering of Nebulized Metal-Phenolic Capsules for Controlled Pulmonary Deposition.

Particle-based pulmonary delivery has great potential for delivering inhalable therapeutics for local or systemic applications. The design of particles with enhanced aerodynamic properties can improve lung distribution and deposition, and hence the efficacy of encapsulated inhaled drugs. This study describes the nanoengineering and nebulization of metal-phenolic capsules as pulmonary carriers of small molecule drugs and macromolecular drugs in lung cell lines, a human lung model, and mice. Tuning the aerodynamic diameter by increasing the capsule shell thickness (from ≈100 to 200 nm in increments of ≈50 nm) through repeated film deposition on a sacrificial template allows precise control of capsule deposition in a human lung model, corresponding to a shift from the alveolar region to the bronchi as aerodynamic diameter increases. The capsules are biocompatible and biodegradable, as assessed following intratracheal administration in mice, showing >85% of the capsules in the lung after 20 h, but <4% remaining after 30 days without causing lung inflammation or toxicity. Single-cell analysis from lung digests using mass cytometry shows association primarily with alveolar macrophages, with >90% of capsules remaining nonassociated with cells. The amenability to nebulization, capacity for loading, tunable aerodynamic properties, high biocompatibility, and biodegradability make these capsules attractive for controlled pulmonary delivery.

Current Progresses in Metal-based Anticancer Complexes as Mammalian TrxR Inhibitors.

Reactive oxygen species (ROS) are produced as normal products of cellular metabolism, which are essential for numerous cell biological functions. Due to aberrant metabolism, oncogenic signaling activation and mitochondrial dysfunction, cancer cells generate excessive ROS that cause severe oxidative damage, finally leading to tumor cell death. Thioredoxin reductase (TrxR), as an important ROS-scavenging enzyme, is overexpressed in various human tumors and plays an important role in regulating intracellular redox homeostasis to protect cancer cells from cell death induced by substantial ROS. Hence, TrxR has emerged as a promising target for anticancer agent development. Currently, metallodrugs with anticancer activity, especially gold- and platinum-complexes, have an enormous impact on clinical cancer chemotherapy. This review provides a comprehensive overview of various metal complexes (gold, platinum, ruthenium, rhodium, iridium, iron, palladium, silver, antimony, bismuth, tin) targeting mammalian TrxR and discusses their cytotoxicity in tumor cells.

Relationship between total phenolic contents and biological properties of propolis from 20 different regions in South Korea.

BACKGROUND: Propolis (or bee glue), collected from botanical sources by honey bee, has been used as a popular natural remedies in folk medicine throughout the world. This study was conducted to assess growth inhibitory effects of ethanol extracts of propolis (EEPs) from 20 different regions in South Korea on human intestinal bacteria as well as their human ß-amyloid precursor cleavage enzyme (BACE-1), acetylcholinesterase (AChE) inhibitory, antioxidant, antiproliferative, and anti-human rhinovirus activities. METHODS: The Bonferroni multiple-comparison method was used to test for significant differences in total polyphenol and flavonoid contents among EEP samples using SAS 9.13 program. Correlation coefficient (r) analysis of the biological activities of EEP samples was determined using their 50 % inhibition concentration or minimal inhibitory concentration values and their polyphenol or flavonoid contents in 20 native Korean EEP samples. RESULTS: The amounts of total polyphenol and flavonoids in the Korean EEP samples ranged from 49 to 239 mg gallic acid equivalent (GAE)/g EEP (Brazilian, Chinese, and Australian samples, 127-142 mg GAE/g EEP) and from 21 to 50 mg quercetin equivalent (QE)/g EEP (Brazilian, Chinese, and Australian samples, 33-53 mg QE/g EEP), respectively. Correlation coefficient analysis showed that total polyphenol contents may be negatively correlated with 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (r = -0.872) and total flavonoid content has no correlation with the activity (r = 0.071). No direct correlation between BACE-1 inhibition, AChE inhibition, or antiproliferative activity and total polyphenol or total flavonoid content in Korean EEP samples was found. Gram-positive and Gram-negative bacteria were observed to have different degrees of antimicrobial susceptibility to the EEP samples examined, although ciprofloxacin susceptibility among the bacterial groups did not differ greatly. CONCLUSIONS: Further studies will warrant possible applications of propolis as potential therapeutic BACE-1 blocker, antioxidant, antiproliferative agent, and antimicrobial agent.