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Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.
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Apoptosis , Ivermectina , Larva , Mitocondrias , Receptores Notch , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Pez Cebra , Animales , Ivermectina/análogos & derivados , Ivermectina/toxicidad , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Larva/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Receptores Notch/metabolismo , Insecticidas/toxicidad , Vasos Sanguíneos/efectos de los fármacosRESUMEN
Dimefluthrin (DIM) is a commonly utilized sanitary insecticide, predominantly employed for indoor pest management within residential and public environments directly interacting with human habitation. However, the usage of DIM is escalating with increasing mosquito resistance, prompting concerns about its health risks. Here, using zebrafish as a research model, we systematically evaluated DIM's impact on human health. Findings revealed significant health hazards during embryonic development, including reduced hatching rates, shortened body lengths, and organ malformations, notably affecting the heart. It was explored the mechanism of DIM-induced cardiotoxicity in zebrafish, and histopathological analyses revealed that DIM resulted in ventricular linearization in zebrafish embryos. Antioxidant enzyme activities were reduced and cardiac reactive oxygen species (ROS) accumulated after DIM exposure, suggesting clear signs of oxidative stress. Additionally, acridine orange (AO) staining and caspase-3 immunofluorescence demonstrated cardiac apoptosis in Tg (kdrl: EGFP) zebrafish. qPCR analysis implied that DIM induced apoptosis via the p53/Caspase pathway by up-regulating the expression levels of p53, cytochrome C (cyto-C), caspase-9, and caspase-3. Together, our work provided a systematic perspective on the cardiotoxicity of sanitary pesticides, which could offer opportunities for future risk management.
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Retinal fibrosis is one of the major features of Diabetic retinopathy. Our recent research has shown that Poldip2 can affect early DR through oxidative stress, but whether or not Poldip2 would regulate retinal fibrosis during DR development is still enigmatic. Here, Diabetic Sprague-Dawley (SD) rats were induced with STZ and treated with AAV9-Poldip2shRNA, while human retinal pigment epithelial cells (ARPE-19) were treated with high glucose (HG) or Poldip2 siRNA. We identified that in STZ-induced DR rats and ARPE-19 treated with high glucose, the expression of Poldip2, TGFß1, P-SMAD3/SMAD3, MMP9, COL-1, FN, and CTGF increased while the expression of Cadherin decreased. However, deleting Poldip2 inhibited the TGF-ß1/SMAD3 signaling pathway and attenuated the above protein expression in vivo and in vitro. Mechanistically, we found that Poldip2 promotes the activation of SMAD3, and facilitates its nuclear translocation through interacting with it, and significantly enhances the expression of fibrosis makers. Collectively, it was identified that Poldip2 is a novel regulator of DR fibrosis and it is expected to become a therapeutic target for PDR.
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Natural pyrethrins (NPs) are insecticidal compounds isolated and extracted from pyrethrum flowers and are primarily use to control sanitary pests. The lungs become the main target after exposure, and its use may pose potential hazards to respiratory health. Therefore, in this paper, the toxic effects of NPs on human lung cells A549 were investigated and the risk of respiratory toxicity of NPs was studied using zebrafish swim bladder as a model. The results showed that NPs induced cytotoxicity, caused oxidative DNA damage and triggered mitochondria-mediated apoptosis. In addition, exposure to NPs decreased zebrafish embryo survival, hatchability, and heartbeat, and may inhibit normal swim bladder development by disrupting Wnt and Hedgehog signaling pathways. In conclusion, our results suggest that NPs can induce cytotoxicity in A549 in vitro and developmental toxicity in zebrafish in vivo. This study provides a conceptual basis for understanding the mechanisms of toxicity of NPs and assessing respiratory health risks in humans.
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Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. In vitro studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a H2O2-induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further in vivo studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood-retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility in vivo. In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.
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Enfermedades Autoinmunes , Curcumina , Nanopartículas , Estrés Oxidativo , Povidona , Uveítis , Animales , Curcumina/administración & dosificación , Curcumina/farmacología , Curcumina/química , Curcumina/uso terapéutico , Uveítis/tratamiento farmacológico , Uveítis/inmunología , Uveítis/metabolismo , Povidona/química , Povidona/administración & dosificación , Nanopartículas/administración & dosificación , Nanopartículas/química , Humanos , Enfermedades Autoinmunes/tratamiento farmacológico , Línea Celular , Estrés Oxidativo/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Ratas , Femenino , Ratas Endogámicas Lew , Barrera Hematorretinal/efectos de los fármacos , Barrera Hematorretinal/metabolismo , MasculinoRESUMEN
To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16-13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.
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Retinopatía Diabética , Encuestas Nutricionales , Humanos , Retinopatía Diabética/mortalidad , Masculino , Femenino , Anciano , Estados Unidos/epidemiología , Causas de Muerte , Anciano de 80 o más Años , Persona de Mediana Edad , Factores de Riesgo , Modelos de Riesgos Proporcionales , Diabetes Mellitus/mortalidadRESUMEN
Natural pyrethrins are widely used in agriculture because of their good insecticidal activity. Meanwhile, natural pyrethrins play an important role in the safety evaluation of pyrethroids as precursors for structural development of pyrethroid insecticides. However, there are fewer studies evaluating the neurological safety of natural pyrethrins on non-target organisms. In this study, we used SH-SY5Y cells and zebrafish embryos to explore the neurotoxicity of natural pyrethrins. Natural pyrethrins were able to induce SH-SY5Y cells damage, as evidenced by decreased viability, cycle block, apoptosis and DNA damage. The apoptotic pathway may be related to the involvement of mitochondria and the results showed that natural pyrethrins induced a rise in Capase-3 viability, Ca2+ overload, a decrease in adenosine triphosphate (ATP) and a collapse of mitochondrial membrane potential in SH-SY5Y cells. Natural pyrethrins may mediate DNA damage in SH-SY5Y cells through oxidative stress. The results showed that natural pyrethrins induced an increase in reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and catalase (CAT) activity, and induced a decrease in glutathione peroxidase (GPx) activity in SH-SY5Y cells. In vivo, natural pyrethrins induced developmental malformations in zebrafish embryos, which were mainly characterized by pericardial edema and yolk sac edema. Meanwhile, the results showed that natural pyrethrins induced damage to the Huc-GFP axis and disturbed lipid metabolism in the head of zebrafish embryos. Further results showed elevated ROS levels and apoptosis in the head of zebrafish embryos, which corroborated with the results of the cell model. Finally, the results of mRNA expression assay of neurodevelopment-related genes indicated that natural pyrethrins exposure interfered with their expression and led to neurodevelopmental damage in zebrafish embryos. Our study may raise concerns about the neurological safety of natural pyrethrins on non-target organisms.
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Embrión no Mamífero , Piretrinas , Pez Cebra , Animales , Pez Cebra/embriología , Piretrinas/toxicidad , Embrión no Mamífero/efectos de los fármacos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Insecticidas/toxicidad , Daño del ADN/efectos de los fármacos , Línea Celular Tumoral , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
PURPOSE: Uveitis is a common, sight-threatening inflammatory ocular disease and is the main cause of blindness, which is caused by autoimmune response, infection, and injury. The contribution of 14-3-3ζ in uveitis remains obscure. This study aims to investigate the role of 14-3-3ζ in regulating ferroptosis in retinal inflammation and its contribution to uveitis. METHODS: A lipopolysaccharide (LPS)-induced uveitis mouse model and BV-2 cell line were used to examine the effect of LPS stimulation on the expression of 14-3-3ζ and ferroptosis in microglia. The expression of heme oxygenase-1 (HO-1) was also analyzed to understand its role in promoting microglial ferroptosis. RESULTS: We found that LPS stimulation increased the expression of 14-3-3ζ and promoted ferroptosis in microglia. Additionally, 14-3-3ζ was found to promote microglial ferroptosis by stabilizing the expression of HO-1. These findings suggest that the 14-3-3ζ/HO-1 axis plays a crucial role in promoting microglial ferroptosis in retinal inflammation. CONCLUSION: The study provides valuable insights into the mechanisms underlying uveitis and highlights the potential of the 14-3-3ζ/HO-1 axis as a therapeutic target for the disease. Further research in this area could lead to the development of preventive and therapeutic strategies for uveitis.
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This cross-sectional study investigated the association between glaucoma and B vitamin dietary intake. A total of 5025 enrolled individuals participated in self-reported glaucoma questionnaire and 3264 participated in International Society Geographical and Epidemiological Ophthalmology (ISGEO) criteria. In self-reported glaucoma, the risk of having self-reported glaucoma was lower in the third quartile of vitamin B1 intake (odds ratio [odds ratio [OR] 0.63, 95% confidence interval [CI] 0.40-0.97), and P trend (P trend = 0.004) for vitamin B12 was significant; in males, the third quartile of vitamin B1 intake (OR 0.44, 95% CI 0.24-0.83) and the fourth quartile of vitamin B2 intake (OR 0.39, 95% CI 0.17-0.89) were associated with a lower risk. In glaucoma based on ISGEO criteria, the increase of niacin intake (OR 0.94, 95% CI 0.89-0.99) was negatively associated with the odds of self-reported glaucoma. After sex-stratified analysis, the third quartile of vitamin B6 intake (OR 0.21, 95% CI 0.08-0.60) in males were associated with reduced odds of glaucoma. The restricted cubic spline analysis revealed a nonlinear association of vitamin B2 (p for nonlinearity = 0.04) and B9 (p for nonlinearity = 0.024) intake with glaucoma diagnosed by ISGEO criteria in females.
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Glaucoma , Complejo Vitamínico B , Femenino , Masculino , Humanos , Estudios Transversales , Riboflavina , Glaucoma/epidemiología , TiaminaRESUMEN
High-temperature-resistant and self-lubricating polymer composites with long life and high reliability are increasingly indispensable in the aerospace field. Herein, ZIF-67 grown on the MXene lamella was successfully prepared, and ZIF-67@MXene/PI composites with a regular layered structure were obtained by a hot-pressing three-dimensional network aerogel. It was revealed that incorporating ZIF-67@MXene into PI dramatically reduced the friction and abrasion with elevated temperatures. Largely, aerogel walls always paralleled the sliding direction by compressing, providing a significant antifriction effect. More notably, the presence of a vigorous tribofilm composed of a PI matrix and a diamond-type lattice MOF-modified MXene provided rolling and sliding interface friction under high temperatures, simultaneously. In addition, the uniform tribofilm with a thickness of about 200 nm can effectively avoid the direct contact of the friction pair during the sliding process. Hence, the combination of the constructed multiscale nanocomposites and nanostructured tribofilm with outstanding tribological performance endow the material potentially useful in reducing energy consumption, thus addressing the energy wastage problem caused by friction.
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Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.
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The pesticide acetochlor (ACT) is a chiral isomer commonly detected in the global environment, yet its specific impacts on liver function remain poorly understood. We utilized zebrafish and L02 cells as research models to comprehensively investigate how ACT and its chiral isomers affect the liver. Our investigations unveiled that the R, Rac, and S isomers of ACT disrupt hepatic lipid transport, catabolism, and synthesis, leading to delayed yolk sac absorption and the accumulation of lipids in zebrafish embryos. These isomers induce oxidative stress in the liver of zebrafish embryos, reducing antioxidant levels and enzyme activity. The accumulated lipids in the liver render it susceptible to oxidative stress, further exacerbating hepatocyte damage. Hepatocyte damage manifests as extensive vacuolization of liver cells and alterations in liver morphology, which are induced by R, Rac, and S. Furthermore, we elucidated the molecular mechanisms underpinning the disturbance of hepatic lipid metabolism by R, Rac, and S in L02 cells. These compounds stimulate lipid synthesis through the upregulation of the AMPK/SREBP-1c/FAS pathway while inhibiting lipolysis via downregulation of the PPAR-α/CPT-1a pathway. Remarkably, our results highlight that S exhibits significantly higher hepatotoxicity in comparison to R. This study provides valuable insights into the hepatic effects of ACT chiral isomers.
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Hígado , Toluidinas , Pez Cebra , Animales , Hígado/metabolismo , Hepatocitos , Metabolismo de los Lípidos , LípidosRESUMEN
OBJECTIVES: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort. METHODS: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence (net drift, % per year), annual percentage change of prevalence within each age group (local drift, % per year), fitted longitudinal age-speciï¬c rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019. RESULTS: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift, higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts. CONCLUSIONS: Although a favourable overall temporal trend (net drift) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing.
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Carga Global de Enfermedades , Enfermedades Musculoesqueléticas , Adulto , Adolescente , Humanos , Femenino , Prevalencia , Factores de Riesgo , Estudios de Cohortes , Enfermedades Musculoesqueléticas/epidemiología , Salud Global , Años de Vida Ajustados por Calidad de Vida , IncidenciaRESUMEN
Emamectin benzoate (EMB) is an insecticide for the control of agricultural lepidoptera pests, and also an anti-parasiticide for the control of exoparasites in aquaculture industry. Increased studies suggest that EMB could cause toxicity to non-targeted organisms, but its immunotoxicity to human remains unclear. In this study, zebrafish were used to investigate the immunotoxic effects induced by environmentally relevant doses of EMB. We observed that EMB exposure led to embryo mortality and delayed hatching, as well as increased malformations. Meanwhile, zebrafish exposed to EMB exhibited a significant decrease in the number of neutrophils and macrophages. In addition, untargeted metabolomics approach was developed to elucidate the mechanism of EMB-induced immunotoxicity. We found that a total of 10 shared biomarkers were identified in response to EMB exposure. Furthermore, pathway analysis identified glycerophospholipid metabolism was the most relevant pathway. Within this pathway, it was observed abnormal increases in glycerol 3-phosphate content, which could be attributed to the increased expression of GK5 and decreased expression of GPAT3. Our study provided novel and robust perspectives, which showed that EMB exposure to zebrafish embryos could cause metabolic disturbances that adversely affected development and immune system.
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Insecticidas , Pez Cebra , Animales , Humanos , Ivermectina/toxicidad , Insecticidas/toxicidad , MacrófagosRESUMEN
Acetochlor (ACT) is a widely detected pesticide globally, and the neurotoxic effects of its chiral isomers on humans and environmental organisms remain uncertain. Zebrafish were used to study the neurotoxicity of ACT and its chiral isomers. Our study reveals that the R-ACT, Rac-ACT, and S-ACT induce neurotoxicity in zebrafish larvae by impairing vascular development and disrupting the blood-brain barrier. These detrimental effects lead to apoptosis in brain cells, hindered development of the central nervous system, and manifest as altered swimming behavior and social interactions in the larvae. Importantly, the neurotoxicity caused by the S-ACT exhibits the most pronounced impact and significantly diverges from the effects induced by the R-ACT. The neurotoxicity associated with the Rac-ACT falls intermediate between that of the R-ACT and S-ACT. Fascinatingly, we observed a remarkable recovery in the S-ACT-induced abnormalities in BBB, neurodevelopment, and behavior in zebrafish larvae upon supplementation of the Wnt/ß-catenin signaling pathway. This observation strongly suggests that the Wnt/ß-catenin signaling pathway serves as a major target of S-ACT-induced neurotoxicity in zebrafish larvae. In conclusion, S-ACT significantly influences zebrafish larval neurodevelopment by inhibiting the Wnt/ß-catenin signaling pathway, distinguishing it from R-ACT neurotoxic effects.
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Toluidinas , Pez Cebra , Humanos , Animales , Pez Cebra/metabolismo , Larva , Toluidinas/toxicidad , Toluidinas/metabolismo , Barrera HematoencefálicaRESUMEN
OBJECTIVES: This review outlines the function of oxidative stress in DR and discusses therapeutic strategies to treat DR with antioxidants. METHODS: Published papers on oxidative stress in DR and therapeutic strategies to treat DR with antioxidants were collected and reviewed via database searching on PubMed. RESULTS: The abnormal development of DR is a complicated process. The pathogenesis of DR has been reported to involve oxidative stress, despite the fact that the mechanisms underlying this are still not fully understood. Excessive reactive oxygen species (ROS) accumulation can damage retina, eventually leading to DR. Increasing evidence have demonstrated that antioxidant therapy can alleviate the degeneration of retinal capillaries in DR. CONCLUSION: Oxidative stress can play an important contributor in the pathogenesis of DR. Furthermore, animal experiments have shown that antioxidants are a beneficial therapy for treating DR, but more clinical trial data is needed.
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Diabetes Mellitus , Retinopatía Diabética , Animales , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Retinopatía Diabética/tratamiento farmacológico , Estrés Oxidativo , Especies Reactivas de Oxígeno , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
BACKGROUND: EAU is an inflammatory disease usually characterized by autoinflammation and autoimmunity and is aggravated by excessive generation of ROS. Conventional hormone therapy often has more adverse effects. It is urgent to find a therapeutic drug with higher efficiency and fewer adverse effects. METHODS: We developed an Fe-curcumin nanozyme in which natural antioxidants coordinate with Fe3+ to form nanoparticles with excellent solubility for directing anti-inflammatory and ROS scavenging effects to treat EAU. Several experiments were used to detect the characteristics of nanozymes. EAU model rats were used to detect the abilities of decreasing autoinflammation and autoimmunity. PBMCs were used to detect the ability to inhibit cell proliferation. RESULTS: Free radical scavenging experiments showed that nanozymes decreased the level of free radicals at low concentrations. In vitro and in vivo experiments revealed that the group treated with Fe-curcumin nanozymes had lower inflammatory reactions and ROS levels than the control group, as reflected by the downregulated levels of several critical inflammatory cytokines, such as IFN-γ, IL-17, and TNF-α; decreased H2O2 release; inhibited proliferation of Th1 and Th17 cells; and alleviated pathological changes in the eye. Importantly, the Fe-curcumin nanozyme was detected in the retina using Prussian blue staining. Additionally, Fe-curcumin nanozyme is noncytotoxic when directing these biological activities. CONCLUSION: This study has demonstrated the feasibility of using the Fe-curcumin nanozyme as a nanodrug to inhibit inflammatory reactions and scavenge ROS in the treatment of EAU, indicating that it may serve as a promising therapeutic agent in clinical treatment.
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PURPOSE: To screen for the differentially expressed genes in experimental retinal detachment rats, and to explore the expression of S100 calcium-binding protein A9 and Toll-like receptor 4 in the vitreous of rhegmatogenous retinal detachment patients. METHODS: Three rats of experimental retinal detachment and three normal rats were enrolled in the study. Transcriptomics (RNAseq) sequencing technology was used to screen differentially expressed genes in the retinas of the experimental retinal detachment group and the normal group. The selected differentially expressed genes for gene ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed. In addition, the vitreous of 15 patients with rhegmatogenous retinal detachment and six patients with the control group were collected. The expressions of S100 calcium-binding protein A9 and Toll-like receptor 4 were detected by Elisa, and the differences in expression levels were analyzed statistically. RESULTS: A total of 198 differentially expressed genes were screened by RNAseq sequencing, including 118 upregulated genes and 80 downregulated genes. Kyoto Encyclopedia of Genes and Genomes analysis confirmed that the most enriched pathway was the mitogen-activated protein kinase signaling pathway. Compared to the normal group, the expressions of suppressor of cytokine signaling-3, Storkhead box-2, S100 calcium-binding protein A9, Spi-1 proto-oncogene, phosphodiesterase 1B, and kinesin-light chain 1 mRNA in the retinas of the experimental retinal detachment rats were up-regulated, and the expressions of Max interacting protein 1 and the voltage-gated sodium 1 were down-regulated. Compared to the control group, the expressions of S100 calcium-binding protein A9 and Toll-like receptor 4 were upregulated by Elisa in the vitreous humor of rhegmatogenous retinal detachment patients with a statistically significant difference (p all <.05). CONCLUSION: The differentially expressed genes of experimental retinal detachment rats were suppressor of cytokine signaling-3, Storkhead box-2, S100 calcium-binding protein A9, Spi-1 proto-oncogene, phosphodiesterase 1B, kinesin-light chain 1, Max interacting protein 1, voltage-gated sodium 1, etc. The differences of S100 calcium-binding protein A9 and Toll-like receptor 4 expressions between the rhegmatogenous retinal detachment patients and the control group were statistically significant, indicating that they may play a potential role in the inflammatory process of rhegmatogenous retinal detachment.
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Calgranulina B , Desprendimiento de Retina , Receptor Toll-Like 4 , Animales , Humanos , Ratas , Proteínas de Unión al Calcio , Citocinas/metabolismo , Perfilación de la Expresión Génica , Cinesinas/genética , Hidrolasas Diéster Fosfóricas/metabolismo , Desprendimiento de Retina/genética , Desprendimiento de Retina/metabolismo , Sodio/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismoRESUMEN
Dry eye disease (DED) is a common disorder of tear secretion on the ocular surface caused by multiple factors with dry eyes as the main symptom, but until now studies focusing on relationship between local meteorological factors and ocular surface diseases in Urumqi are very limited. Besides, the effects of long-term and extreme meteorological factors on DED and the lag effect have not been fully evaluated. Electronic case information of 9970 DED outpatients from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) between January 1, 2013, and December 31, 2020, was screened and analyzed. We used a time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) to fit the effects of exposure to different meteorological factors and extreme weather on DED outpatient visits. Subgroup analyses were further performed for gender, age, and season. The results showed that exposure to extremely low mean temperature (P1:RR = 1.18), atmospheric pressure (P1:RR = 1.11), and extremely high relative humidity (P99:RR = 1.35) were the risk factors, while extremely high atmospheric pressure (P90:RR = 0.883) and extremely low humidity (P10:RR = 0.856) appeared to have a positive effect on reduced risk of DED. Relative humidity exhibited a 1-day lag effect (RR = 1.06). Increased mean temperature positively affected female DED patients (RR = 0.761) with similar effects in the cold season (RR = 0.926). However, elevated relative humidity had a negative effect on female patients (RR = 1.14). We conducted the first large sample size time-series analysis study in this major city at the farthest distance from the ocean in the world and in northwest China, confirming the association of DED outpatient visits with the remaining three meteorological factors except wind speed in Urumqi, and a larger sample size multi-center epidemiological study with a longer duration is still needed.