Inhibition of NLRP3 inflammasome by MCC950 under hypoxia alleviates photoreceptor apoptosis via inducing autophagy in Müller glia.

NLRP3 inflammasome activation has emerged as a critical initiator of inflammatory response in ischemic retinopathy. Here, we identified the effect of a potent, selective NLRP3 inhibitor, MCC950, on autophagy and apoptosis under hypoxia. Neonatal mice were exposed to hyperoxia for 5 days to establish oxygen-induced retinopathy (OIR) model. Intravitreal injection of MCC950 was given, and then autophagy and apoptosis markers were assessed. Retinal autophagy, apoptosis, and related pathways were evaluated by western blot, immunofluorescent labeling, transmission electron microscopy, and TUNEL assay. Autophagic activity in Müller glia after NLRP3 inflammasome inhibition, together with its influence on photoreceptor death, was studied using western blot, immunofluorescence staining, mRFP-GFP-LC3 adenovirus transfection, cell viability, proliferation, and apoptosis assays. Results showed that activation of NLRP3 inflammasome in Müller glia was detected in OIR model. MCC950 could improve impaired retinal autophagic flux and attenuate retinal apoptosis while it regulated the retinal AMPK/mTOR/ULK-1 pathway. Suppressed autophagy and depressed proliferation capacity resulting from hypoxia was promoted after MCC950 treatment in Müller glia. Inhibition of AMPK and ULK-1 pathway significantly interfered with the MCC950-induced autophagy activity, indicating MCC950 positively modulated autophagy through AMPK/mTOR/ULK-1 pathway in Müller cells. Furthermore, blockage of autophagy in Müller glia significantly induced apoptosis in the cocultured 661W photoreceptor cells, whereas MCC950 markedly preserved the density of photoreceptor cells. These findings substantiated the therapeutic potential of MCC950 against impaired autophagy and subsequent apoptosis under hypoxia. Such protective effect might involve the modulation of AMPK/mTOR/ULK-1 pathway. Targeting NLRP3 inflammasome in Müller glia could be beneficial for photoreceptor survival under hypoxic conditions.

Diagnostic ability of the combination of retinal microvasculature evaluation and static automated perimetry for early primary open-angle glaucoma.

PURPOSE: To investigate the diagnostic ability of retinal superficial vasculature evaluation by optic coherence tomography angiography (OCTA) combined with visual field (VF) testing for early primary open-angle glaucoma (POAG). PATIENTS AND METHODS: In this cross-sectional study, 84 participants were included, including 11 in the ocular hypertension (OHT) group, 11 in the preperimetric POAG (pre-POAG) group, 29 in the early POAG group and 33 in the control group. All participants underwent 6 × 6 mm2 scans of macula and optic nerved head by optic coherence tomography (OCT) and OCTA, along with white-on-white and blue-on-yellow VF testing by static automated perimetry. The ability of diagnosing early glaucoma by either various examinations separately or combination of examinations in both terms of function and structure was studied using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: The superficial retinal vessel densities (VD) in peri-nasal, para-temporal, peri-temporal and peri-inferior regions around the macula, as well as vessel area densities (VAD) in all peripapillary regions, were significantly different among the four groups, with lower VD or VAD in the early POAG patients compared to the normal individuals. The diagnostic ability of peripapillary superficial retinal VAD alone or VF testing alone was limited for early POAG only. However, the combination of these two was more effective in distinguishing normal individuals from OHT subjects or pre-POAG patients without VF defects, with better performance than the combination of peripapillary retinal nerve fiber layer (RNFL) thickness and VF indicators. CONCLUSIONS: Peripapillary retinal vessel densities were generally lower in early POAG patients compared to normal individuals. The combination of peripapillary superficial retinal VAD by OCTA with white-on-white VF testing improved the ability to distinguish POAG patients at early stage without function impairment, which may help in providing reference and guidance for the following-up and treatment of suspected POAG patients.

Prokaryotic Expression, Purification, and Antibacterial Activity of the Hepcidin Peptide of Crescent Sweetlips (Plectorhinchus cinctus).

The hepcidin peptide of crescent sweetlips (Plectorhinchus cinctus) is a cysteine-rich, cationic antimicrobial peptide that plays a crucial role in the innate immune system's defense against invading microbes. The aim of this study was to identify the optimal parameters for prokaryotic expression and purification of this hepcidin peptide and characterize its antibacterial activity. The recombinant hepcidin peptides were expressed in Escherichia coli strain Arctic Express (DE3), with culture and induction conditions optimized using response surface methodology (RSM). The obtained hepcidin peptides were then purified before tag cleavage, and their antibacterial activity was determined. The obtained results revealed that induction temperature had the most significant impact on the production of soluble recombinant peptides. The optimum induction conditions were determined to be an isopropylthio-ß-galactoside (IPTG) concentration of 0.21 mmol/L, induction temperature of 18.81 °C, and an induction time of 16.01 h. Subsequently, the recombinant hepcidin peptide was successfully purified using Ni-IDA affinity chromatography followed by SUMO protease cleavage. The obtained hepcidin peptide (without His-SUMO tag) demonstrated strong antimicrobial activity in vitro against V. parahaemolyticus, E. coli, and S. aureus. The results showed prokaryotic (E. coli) expression is a feasible way to produce the hepcidin peptide of crescent sweetlips in a cost-effective way, which has great potential to be used as an antimicrobial agent in aquaculture.

Inhibition of vascular endothelial growth factor alleviates neovascular retinopathy with regulated neurotrophic/proinflammatory cytokines through the modulation of DBI-TSPO signaling.

Diazepam binding inhibitor (DBI)-translocator protein (18kDa) (TSPO) signaling in the retina was reported to possess coordinated macroglia-microglia interactions. We investigated DBI-TSPO signaling and its correlation with vascular endothelial growth factor (VEGF), neurotrophic or inflammatory cytokines in neovascular retinopathy, and under hypoxic conditions. The vitreous expression of DBI, VEGF, nerve growth factor (NGF), and interleukin-1beta (IL-1ß) were examined in proliferative diabetic retinopathy (PDR) patients with or without anti-VEGF therapy and nondiabetic controls. Retinal DBI-TSPO signaling and the effect of the anti-VEGF agent were evaluated in a mouse model of oxygen-induced retinopathy (OIR). Interactions between Müller cell-derived VEGF and DBI, as well as cocultured microglial cells under hypoxic conditions, were studied, using Western blot, real-time RT-PCR, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunofluorescent labeling. Results showed that vitreous levels of DBI, VEGF, NGF, and IL-1ß were significantly higher in PDR patients compared with controls, which further changed after anti-VEGF therapy. A statistical association was found between vitreous DBI and VEGF, NGF, IL-1ß, and age. The application of the anti-VEGF agent in the OIR model induced retinal expression of DBI and NGF, and attenuated inflammation and microglial cell activation. Inhibition of Müller cell-derived VEGF could increase its DBI expression under hypoxic conditions, while the DBI-TSPO signaling pathway is essential for anti-VEGF agents exerting anti-inflammatory and neuroprotective effects, as well as limiting inflammatory magnitude, promoting its neurotrophin production and anti-inflammatory (M2) polarization in microglial cells. These findings suggest the beneficial effect of anti-VEGF therapy on inflammation and neurotrophy of retinal glial cells through modulation of the DBI-TSPO signaling pathway.

Analysis of choroidal thickness in juvenile systemic lupus erythematosus and its correlation with laboratory tests.

BACKGROUND: The aim of this study is to investigate the alterations of choroidal thickness (CT) in juvenile systemic lupus erythematosus (JSLE) using enhanced depth imaging optical coherence tomography (EDI-OCT). We also aimed to assess whether CT parameters correlated with systemic health status in JSLE patients. METHODS: JSLE patients and age- and sex-matched healthy subjects were recruited. A detailed ophthalmological examination was applied to all participants. CT measurements were acquired in the macular region using EDI-OCT. Moreover, a spectrum of laboratory tests was examined to evaluate the systemic conditions, and the Th1/Th2/Th17/Treg cytokine profiles in the peripheral blood were also analyzed in JSLE group. RESULTS: A total of 45 JSLE patients with no visual impairment and 50 healthy individuals were enrolled in the study. CT values in the macular region were decreased in JSLE patients when compared with healthy controls, even adjusting for age, axial length and refraction. There were no significant correlations between CT and cumulative dose of hydroxychloroquine or duration of hydroxychloroquine use (all P > 0.05). The average macular, temporal and subfoveal CT in JSLE group was negatively correlated with IL-6 and IL-10 (all P < 0.05), but had no significant correlations with other laboratory results (all P > 0.05). CONCLUSIONS: JSLE patients without ocular involvement may have significant variations in choroidal thickness at the macular area. Choroidal alterations might be associated with the systemic cytokine profiles in JSLE.

Polyoxometalate K6[P2Mo18O62] Inactivates Escherichia coli O157:H7 by Inducing recA Expression and Apoptosis-like Bacterial Death.

Polyoxometalates have emerged as promising bactericidal agents. In the current study, the bactericidal activity of polyoxometalate K6[P2Mo18O62] against Escherichia coli (E. coli) O157:H7 and its possible underlying mechanisms were explored. The obtained results demonstrated that K6[P2Mo18O62] could effectively kill E. coli O157:H7 at millimolar levels. Moreover, K6[P2Mo18O62] treatment also induced significant increases in recA protein expression and further triggered characteristic apoptosis-like bacterial death events such as DNA fragmentation and phosphatidylserine exposure. In conclusion, polyoxometalate K6[P2Mo18O62] possesses a desirable antibacterial activity, and induction of bacterial apoptosis-like death might be involved in its underlying bactericidal mechanisms.

Quantitative evaluation of retinal and choroidal changes in Fabry disease using optical coherence tomography angiography.

To examine the retinal and choroidal changes in patients with Fabry disease (FD) using optical coherence tomography angiography (OCTA). FD patients and age- and sex-matched healthy subjects were enrolled. A detailed ophthalmological examination was performed for all participants. The retinal thickness, ganglion cell layer with inner plexiform layer (GCIPL) thickness, choroidal thickness (CT), vessel length density (VLD), vessel perfusion density (VPD), and foveal avascular zone (FAZ) were analyzed in a detailed way with OCTA. Moreover, all FD patients underwent several laboratory tests to evaluate systemic conditions. A total of 54 subjects comprising 26 FD patients and 28 normal controls were enrolled. The retinal thickness, GCIPL thickness, and FAZ area showed no significant differences between the two groups (all P > 0.05). Only the superior CT in FD patients was significantly thinner than that in the normal subjects (P = 0.040). The macular VLD and VPD in the FD group were significantly reduced compared with the healthy controls (P = 0.026, P = 0.008). The macular VLD in FD patients had no significant correlations with different laboratory results (all P > 0.05), while the macular VPD were negatively correlated with creatinine (r = - 0.432, P = 0.028) and cystatin C (r = - 0.422, P = 0.032). FD patients may have retinal vascular dropout and choroidal vascular alterations. Analysis of vessel density using OCTA might be useful in the clinical assessment in FD patients.

Evaluation of retinal and choroidal variations in thyroid-associated ophthalmopathy using optical coherence tomography angiography.

BACKGROUND: To investigate the difference in retinal nerve fiber layer (RNFL) thickness, choroidal thickness (CT) and superficial retinal vessels between thyroid-associated ophthalmopathy (TAO) patients and healthy controls. To identify the potential influencing factors for these parameters and evaluate their diagnostic abilities in TAO. METHODS: Twenty active TAO patients, 33 inactive TAO patients and 29 healthy participants were enrolled. TAO patients were divided according to the clinical activity score (CAS). RNFL thickness and CT were measured by HD-OCT, while foveal avascular zone (FAZ), vascular density and perfusion density were measured by optical coherence tomography angiography (OCTA). SPSS software was used for statistical analysis. RESULTS: Active TAO patients had thinner RNFL thickness than the other two groups (P < 0.001, P < 0.001). Both active and inactive TAO patients had significantly higher CT in the macular region (all P < 0.05). The FAZ area in the active TAO group was significantly larger than the other two groups (P = 0.045, P = 0.001). The inactive TAO group had significantly higher vascular density than the other two groups (all P < 0.05). With regard to the perfusion density, significant differences were observed in the temporal and inferior areas (P = 0.045, P = 0.001), as well as the average values (P = 0.032). The FAZ area was positively correlated with intraocular pressure (r = 0.274, P = 0.013), while it was negatively correlated with axial length (r = - 0.344, P = 0.002). The vascular density and perfusion density were not significantly correlated with different clinical variables (all P > 0.05). The AUC analysis indicated these parameters also exhibited a significant discriminatory power in TAO diagnosis. CONCLUSIONS: TAO patients had significant variations in RNFL thickness, choroidal thickness, FAZ area and superficial retinal vessels. These parameters appeared to be potential adjuncts in the evaluation of TAO patients.

Intravitreal ranibizumab or conbercept for retinal arterial macroaneurysm: a case series.

BACKGROUND: There is no consensus for the standard treatment of retinal arterial macroaneurysm (RAM). Intravitreal anti-vascular endothelium growth factor (anti-VEGF) is an alternative treatment option for RAM. The purpose of this study is to describe the clinical efficacy of intravitreal ranibizumab or intravitreal conbercept for retinal arterial macroaneurysm. CASE PRESENTATION: Three cases that presented with symptomatic RAM were treated with intravitreal anti-VEGF agents. Two eyes received two intravitreal ranibizumab injections with a time interval of one month and completed a one-year follow-up, while one eye only received one intravitreal conbercept injection and was followed up for six months. Both the retinal thickness and the visual acuity were significantly improved at the final clinic visit. The macular hemorrhage and edema were resolved. There were no ocular or systemic side effects. CONCLUSIONS: Intravitreal ranibizumab or conbercept might be used as a therapeutic option for symptomatic retinal arterial macroaneurysm patients. Anti-VEGF therapy should be further investigated in a larger series with longer follow-up for this disease profile.

Hydrogen sulfide supplement attenuates the apoptosis of retinal ganglion cells in experimental glaucoma.

Glaucoma is a group of neurodegenerative eye diseases characterized by progressive impairment of visual function due to loss of retinal ganglion cells (RGC). As hydrogen sulfide (H2S) was reported to play a role in the process of glaucomatous neuropathy and improve RGC survival in experimental glaucoma, the authors aimed to investigate the anti-apoptosis effect of H2S supplement in a rat glaucoma model, and further tried to explore the involved factors in the neuroprotection. A chronic ocular hypertension (COH) rat model induced by intracameral injection of cross-linking hydrogel was employed to simulate glaucoma and 288 rats were subjected to experimental procedures in the present study. After 4 weeks of sodium hydrosulfide (NaHS) administration following COH induction, the apoptosis of RGC isolated from experimented rats as well as apoptosis of neurons in ganglion cell layer (GCL), intrinsic apoptotic pathway activity, mitochondrial function, glial activation, NF-κB pathway activity, NADPH oxidase activity, autophagy activity and TNF-α level in retina were evaluated. The results showed that H2S supplement effectively attenuated the apoptosis of RGC in experimental glaucoma, and the neuroprotection by H2S might correlate with preservation of mitochondrial function, attenuation of oxidative stress, suppression of glial activation, inhibition of inflammatory pathways and downregulation of autophagy. Our study indicated that H2S supplement resulted in significant neuroprotection through attenuation of RGC apoptosis which might be linked with multiple factors in experimental glaucoma. The new therapeutic strategy might potentially contribute to benefit glaucoma treatment, which is worth further concerns.

Surgical removal of submacular perfluorocarbon liquid with a 38-gauge flexible cannula combined with internal limiting membrane peeling and intravitreal air tamponade: a case series.

BACKGROUND: To report a case series in which a modified technique was used to remove retained submacular perfluorocarbon liquid (PFCL) secondary to vitreoretinal surgery for rhegmatogenous retinal detachment. CASE PRESENTATION: Four patients who had undergone pars plana vitrectomy for rhegmatogenous retinal detachment were further treated with surgical intervention because of retained submacular PFCL. With a three-port pars plana approach, after the internal limiting membrane peeling with indocyanine green staining, a 38-gauge flexible cannula was used to aspirate the submacular perfluorocarbon bubble, followed by fluid-air exchange and air injection into vitreous cavity. Submacular perfluorocarbon liquid was removed successfully and visual acuity had an improvement in all cases. CONCLUSION: The surgical removal of retained submacular PFCL using a 38-gauge flexible cannula combined with internal limiting membrane peeling and intravitreal air tamponade may provide anatomical and visual satisfactory outcomes.

Analysis of choroidal thickness in ocular hypertensive patients using enhanced depth imaging optical coherence tomography.

This study aimed to compare choroidal thickness between subjects with ocular hypertension (OHT) and normal individuals and explore factors affecting choroidal thickness. This study included 60 untreated newly diagnosed OHT eyes and 60 normal eyes. Choroidal thickness obtained from Cirrus HD-OCT was measured at different locations in the macular and peripapillary regions and compared between the two groups before and after adjusting for potential confounding variables. Regression analysis was performed to figure out factors influencing choroidal thickness. The macular choroidal thickness did not vary significantly between OHT patients and normal controls regardless of locations (all P > 0.05). The average peripapillary choroidal thickness was 167 ± 53 µm in OHT eyes and 185 ± 63 µm in the normal eyes; no significant differences were identified (P = 0.107). Only one of the locations in the temporal area in the OHT group demonstrated significantly thinner peripapillary choroidal thickness as compared to the normal group (P = 0.033). Age was the only significant factor affecting choroidal thickness on multivariate analysis regardless of locations (all P < 0.001). Choroidal thickness of the macular and peripapillary regions in OHT patients is not decreased significantly except one location in the temporal area of the optic disc when comparing with the normal subjects. Anatomic peripapillary choroidal thickness measurements with SD-OCT might be one more tool to track changes in OHT patients.

Comparison of anti-allergic activities of different types of lotus seed resistant starch in OVA-induced mouse model.

Currently, evidence from observational studies suggests dietary fiber intake may be associated with decreased risk of food allergy. As a type of dietary fiber, resistant starch was also widely reported to possess anti-allergic properties. However, there is a relative paucity of studies assessing the influence of resistant starch types on their anti-allergic activity and its possible underlying mechanisms. In the current study, the anti-allergic effects of RS3-type (retrograded starch), RS4-type (chemically modified starch, cross-bonded), and RS5-type (starch-palmitic acid complex) of lotus seed resistant starch were evaluated in the OVA (100 mg/kg)-induced food allergic mice model. The results showed that oral administration of RS3 or RS4 lotus seed resistant starch (0.3 g/100 g b.w.) for 25 days significantly improved adverse symptoms of food allergy such as weight loss, increases in allergy symptom score and diarrhea rate; with significant reduction of serum specific antibody IgE, TNF-α, IL-4 levels and improved Th1/Th2 balance being observed. The mechanism may involve the regulation of lotus seed resistant starch on intestinal flora and the metabolites short-chain fatty acids and bile acids. Taken together, the findings may enhance understanding towards ameliorative effects of resistant starch on food allergy, and offer valuable insights for the exploration of novel anti-allergic bioactive compounds.

TLR4 Inhibition Protects against Retinal Ganglion Cell Damage in Rats with Chronic Ocular Hypertension.

BACKGROUND: This study aims to investigate the protective effect of Toll-like receptor 4 (TLR4) inhibitor Resatorvid (TAK-242) on retinal ganglion cells (RGCs) in a chronic ocular hypertension (COH) rat model, as well as to explore the potential involved mechanisms. METHODS: COH model was built up in rats with a single intracameral administration of cross-linking hydrogel. The expression levels of TLR4, NLR family pyrin domain containing 3 (NLRP3), microglial activation and pro-inflammatory cytokines were evaluated in COH retinas and COH retinas treated with TAK-242 using immunofluorescence staining and Western blot. Additionally, retrograde labeling and neuronal nuclear protein (NeuN) staining were performed to count RGCs. RESULTS: Activated microglia and increased TLR4 expression were observed in the retinas of COH rats. This was accompanied by upregulated expressions of NLRP3, tumor necrosis factor alpha (TNF-α), cytokine interleukin-1ß (IL-1ß) and Interleukin-6 (IL-6). Intravitreal injection of TAK-242 promoted the survival of RGCs by attenuating microglial activation, interfering with the TLR4-NLRP3 pathway and regulating pro-inflammatory cytokines. CONCLUSIONS: Targeting TLR4 inhibition could be a potential therapeutic strategy to protect RGCs from COH damage.

Clinical Efficacy of Preoperative and Intraoperative Intravitreal Ranibizumab as Adjuvant Therapy of Ahmed Glaucoma Valve Implantation Combined with Vitrectomy in the Management of Neovascular Glaucoma with Diabetic Vitreous Hemorrhage.

Neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR) is a devastating ocular disease with poor prognosis. Intravitreal ranibizumab injection (IVR) has been used as adjuvant therapy of surgical interventions preoperatively or intraoperatively. This study aimed to determine the efficacy and safety of combined IVR as adjuvant therapy in treating NVG with vitreous hemorrhage (VH) in PDR. A total of 39 NVG patients with VH (39 eyes) received IVR 3 to 5 days before surgery, and then they were assigned to either pars plana vitrectomy (PPV) + Ahmed glaucoma valve (AGV) implantation (Group 1, n = 22) or PPV + AGV implantation + intraoperative IVR (Group 2, n = 17). Patients were followed up for at least 9 months. Intraocular pressure (IOP), anti-glaucoma medications, best corrected visual acuity (BCVA), surgical success rates and postoperative complications were compared. Results showed that IOP decreased promptly after surgery and was notably maintained at a mid-term follow-up in both groups, and no significant differences were observed (all p > 0.05). Additional intraoperative IVR significantly reduced postoperative recurrent VH and iris neovascularization (p = 0.047, p = 0.025, respectively). There was no remarkable difference in postoperative anti-glaucoma medications, BCVA and complications between two groups (all p > 0.05). In conclusion, preoperative and intraoperative IVR as adjuvant therapy of AGV implantation combined with PPV could be a safe and effective treatment for NVG with VH in PDR. An additional intraoperative anti-VEGF injection could significantly reduce postoperative VH and iris neovascularization.

Oral Administration of Lotus-Seed Resistant Starch Protects against Food Allergy.

Food allergy is a serious food safety and public health issue. However, the medical interventions for allergy treatment are still suboptimal. Recently, the gut microbiome-immune axis has been considered as a promising target to reduce the symptoms of food allergy. In this study, we explore the oral administration of lotus-seed resistant starch as a means to protect against food allergy using an ovalbumin (OVA) sensitization and challenge rodent model. The results obtained showed that lotus-seed resistant starch intervention alleviated the food allergy symptoms (such as reductions in body temperature and allergic diarrhea). Furthermore, lotus-seed resistant starch also attenuated the increase in OVA-specific immunoglobulins and improved Th1/Th2 imbalance in OVA-sensitized mice. These anti-allergic effects might be associated with the actions of lotus-seed resistant starch on intestinal microbiota. Taken together, our findings suggest that daily ingestion of lotus-seed resistant starch might be effective for the alleviation of food allergy.

RNA-seq Analysis Reveals Potential Synergic Effects of Acetate and Cold Exposure on Interscapular Brown Adipose Tissue in Mice.

Brown adipose tissue (BAT) exhibits remarkable morphological and functional plasticity in response to environmental (e.g., cold exposure) and nutrient (e.g., high-fat diet) stimuli. Notably, a number of studies have showed that acetate, the main fermentation product of dietary fiber in gut, profoundly influences the differentiation and activity of BAT. However, the potential synergic or antagonistic effects of acetate and cold exposure on BAT have not been well examined. In the present study, the C57BL/6J mice were treated with acetate at the systemic level before a short period of cold exposure. Physiological parameters including body weight, blood glucose, and Respiratory Exchange Ratio (RER) were monitored, and thermal imaging of body surface temperature was captured. Moreover, the transcriptome profiles of interscapular BAT were also determined and analyzed afterwards. The obtained results showed that acetate treatment prior to cold exposure could alter the gene expression profile, as evidenced by significant differential clusters between the two groups. GO analysis and KEGG analysis further identified differentially expressed genes being mainly enriched for a number of biological terms and pathways related to lipid metabolism and brown adipose activity such as "G-protein-coupled receptor activity", "cAMP metabolic process", "PPAR signaling pathway", and "FoxO signaling pathway". GSEA analysis further suggested that activation status of key pathways including "PPAR signaling pathway" and "TCA cycle" were altered upon acetate treatment. Taken together, our study identified the potential synergistic effect of acetic acid with cold exposure on BAT, which highlighted the positive dietary and therapeutic aspects of acetate.

Molecular cloning of the hepcidin gene from crescent sweetlips (Plectorhinchus cinctus) and characterization of its encoded antimicrobial peptide.

Hepcidin has been identified as an important antimicrobial peptide exerting important innate immunomodulatory activities in many fish species. In the present study, reverse transcription PCR coupled with the rapid amplification of cDNA ends was used to obtain the full-length cDNA of the crescent sweetlips hepcidin gene, which is 829 bp in length and includes an 273 bp ORF encoding a peptide with 90 amino acid residues. Sequence alignment showed a typical RXKR motif and eight conserved cysteine residues in the deduced amino acid sequences. Four disulfide bonds were predicted to form between these eight cysteines, which may stabilize the hairpin structure in hepcidin molecule. Furthermore, phylogenetic analysis showed that the deduced amino acid sequences of crescent sweetlips hepcidin had high sequence homology to hepcidins from fish species of Eupercaria. In addition, the crescent sweetlips hepcidin peptide demonstrated a strong antimicrobial activity in vitro against several types of pathogenic bacteria in fish. In conclusion, the obtained results suggested that crescent sweetlips hepcidin possessed the typical structure similar to other fish hepcidins and had strong antibacterial activity, which showed great potential in the prevention of fish diseases in aquaculture.

Oxidative Stress-Responsive Small Extracellular Vesicles and MicroRNAs in Age-related Macular Degeneration: Biomarkers and Therapeutic Tools.

Age-related macular degeneration (AMD) is the main cause of blurred vision, and oxidative stress is a leading risk factor for AMD pathology. Small extracellular vesicles (EVs) are 50-90 nm membrane microvesicles (MVs) released by several cell types in a controlled fashion and they transfer from cell to cell to mediate disease progression. EVs encapsulate and transfer microRNAs (miRNA) to recipient cells. MiRNAs are small non-coding RNA molecules that inhibit expression and function of targeted mRNAs through miRNA/mRNA interactions in the conserved 3'UTR regions, and in this way they can modulate a variety of physiological and pathological processes. Dysregulation of EVs and their miRNAs cargo from retinal cells is believed to be correlated to a loss of cellular homeostasis and AMD pathology. This review investigates the association between oxidative stress, sEVs, miRNAs, and AMD pathogenesis, and the potential for discovering novel treatment targets for AMD.

Iris metastasis of diffuse large B-cell lymphoma misdiagnosed as primary angle-closure glaucoma: A case report and review of the literature.

BACKGROUND: Lymphoma with intraocular metastasis is an uncommon and serious disease. We describe a case of diffuse large B-cell lymphoma (DLBCL) with iris metastasis. Meanwhile, we refer to published case reports retrieved via a PubMed search to summarize this rare disease. CASE PRESENTATION: Glaucoma and uveitis symptoms were found in the left eye of a 50-year-old woman upon admission to the hospital. After treatment and pathological examination, the iris of her left eye was diagnosed with DLBCL. Given the patient's unfavorable treatment options in the local hospital, primary enucleation was offered as a therapeutic option. CONCLUSIONS: Iris metastasis of systemic lymphoma is an extremely rare ophthalmic disease with poor prognosis. Ophthalmologists should be able to definitively and differentially diagnose eye symptoms and pay attention to systemic conditions to provide a series of optimized treatments.