Unlocking the antiviral potential of rosmarinic acid against chikungunya virus via IL-17 signaling pathway.

Background: The Chikungunya virus is an Alphavirus that belongs to the Togaviridae family and is primarily transmitted by mosquitoes. It causes acute infection characterized by fever, headache, and arthralgia. Some patients also experience persistent chronic osteoarthritis-like symptoms. Dedicated antiviral treatments are currently unavailable for CHIKV. This study aims to explore the potential anti-CHIKV effect of rosmarinic acid using network pharmacology. Methods: This study employed network pharmacology to predict and verify the molecular targets and pathways associated with ROSA in the context of CHIKV. The analysis outcomes were further validated using molecular docking and in vitro experiments. Results: The analysis of CHIKV targets using the Kyoto Encyclopedia of Genes and Genomes and MCODE identified IL-17 as an important pathogenic pathway in CHIKV infection. Among the 30 targets of ROSA against CHIKV, nearly half were found to be involved in the IL-17 signaling pathway. This suggests that ROSA may help the host in resisting CHIKV invasion by modulating this pathway. Molecular docking validation results showed that ROSA can stably bind to 10 core targets out of the 30 identified targets. In an in vitro CHIKV infection model developed using 293T cells, treatment with 60 µM ROSA significantly improved the survival rate of infected cells, inhibited 50% CHIKV proliferation after CHIKV infection, and reduced the expression of TNF-α in the IL-17 signaling pathway. Conclusion: This study provides the first confirmation of the efficacy of ROSA in suppressing CHIKV infection through the IL-17 signaling pathway. The findings warrant further investigation to facilitate the development of ROSA as a potential treatment for CHIKV infection.

A New Mouse Model for Usher Syndrome Crossing Kunming Mice with CBA/J Mice.

BACKGROUND: Previously, we discovered a strain of Kunming mice, referred to as the KMush/ush strain, that exhibited notably abnormal electroretinogram (ERG) readings and elevated thresholds for auditory brainstem responses (ABRs), which resembled the characteristics of Usher Syndrome (USH). We successfully identified the pathogenic genes, Pde6b and Adgrv1, after KMush/ush crossbred with CBA/CaJ mice, referred to as CBA-1ush/ush, CBA-2ush/ush or CBA-2ush/ush. In this investigation, we crossbred KMush/ush and CBA/J mice to establish novel recombinant inbred lines and analysed their phenotypic and genotypic characteristics. METHODS: ERG readings, ABR testing, fundus morphology, histological examination of the retina and inner ear, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, western blotting, DNA sequence analysis and behavioural experiments were performed to assess the phenotypes and genotypes of the progeny lines. RESULTS: No obvious waveforms in the ERG were detected in F1 hybrid mice while normal ABR results were recorded. The F2 hybrids, which were called J1ush/ush or J2ush/ush, exhibited segregated hearing-loss phenotypes. J1ush/ush mice had a retinitis pigmentosa (RP) phenotype with elevated ABR thresholds, whereas J2ush/ush mice exhibited only the RP phenotype. Interestingly, J1ush/ush mice showed significantly higher ABR thresholds than wild-type mice at 28 days post born (P28), and RT-qPCR and DNA-sequencing analysis showed that Adgrv1 gene expression was significantly altered in J1ush/ush mice, but histological analysis showed no significant structural changes in the organ of Corti or spiral ganglia. Further elevation of ABR-related hearing thresholds by P56 manifested only as a reduced density of spiral ganglion cells, which differed significantly from the previous pattern of cochlear alterations in CBA-2ush/ush mice. CONCLUSIONS: We successfully introduced the hearing-loss phenotype of inbred mice with USH into CBA/J mice, which provides a good animal model for future studies on the important physiological roles of the Adgrv1 gene in inner-ear structure and for therapeutic studies targeting Adgrv1-mutated USH.

The efficacy of antiviral treatment in chronic hepatitis B patients with hepatic steatosis.

Background & aims: With a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. Methods: CHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. Results: In total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245-0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. Conclusions: Among CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study.

BACKGROUND: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. METHODS: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. RESULTS: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). CONCLUSIONS: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

SSFVEP as a potential electrophysiological examination for evaluating visual function of fundus diseases with vitreous hemorrhages: a clinical study.

To investigate the sensitivity and potential application of steady-state flash visual evoked potentials (SSFVEP) in assessing the visual function of fundus diseases with vitreous hemorrhage. 18 patients diagnosed with monocular vitreous hemorrhages in the fundus were examined the flash visual evoked potentials (FVEP) and SSFVEP in both eyes. The difference in the P2-wave amplitude of FVEP and the average amplitude of SSFVEP waveform between the diseased eyes and those without vitreous hemorrhage were statistically compared. There was no significant difference in the waveform of FVEP between both eyes. The amplitude of P2-wave from FVEP of the diseased eye was slightly lower than that without vitreous hemorrhage. However, the difference was not statistically significant (P = 0.111). The waveform of SSFVEP in the eye without vitreous hemorrhage showed a towering shape, while that of the diseased eye was flat. The average amplitude of SSFVEP in the diseased eye was statistically lower than that without vitreous hemorrhage (P = 0.036). The difference ratio of SSFVEP amplitude between both eyes was significantly greater than that of FVEP amplitude (P = 0.028). In some fundus diseases with vitreous hemorrhage, SSFVEP had a higher sensitivity than FVEP, providing a novel potential application for visual function assessment.

Disease severity and antiviral response in patients with chronic hepatitis B with non-obese NAFLD.

BACKGROUND: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in patients with chronic hepatitis B (CHB). NAFLD is typically associated with obesity, however, it is increasingly being identified in non-obese patients. This study aimed to investigate disease severity and antiviral response in non-obese patients with CHB with NAFLD (CHB + NAFLD). METHODS: A total of 809 patients with CHB + NAFLD were prospectively recruited and followed up for 3 years. NAFLD was diagnosed by transient elastography and defined as controlled attenuation parameter ≥248 dB/m, in the absence of excessive alcohol intake. Obesity status was defined by the Asian body mass index (BMI) cutoff of 25 kg/m2. Metabolic abnormality was defined by the presence of dyslipidemia, hypertension or diabetes. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1-stage increment. RESULTS: In the total cohort (median age 40 years, 59.0% antiviral-treated), 33.3% were non-obese. Non-obese patients were less metabolically abnormal than obese patients (60.2% vs 72.0%, P = 0.003). After 3-year follow up, the rate of fibrosis progression was comparable between non-obese and obese patients (17.5% vs 21.9% in the total cohort, P = 0.145; 15.7% vs 14.6% in antiviral-treated cohort with persistent viral suppression, P = 0.795). No significant differences in virological and biochemical responses were observed between non-obese and obese patients (P >0.05 for all). CONCLUSIONS: Approximately one third of CHB + NAFLD patients were non-obese. Non-obese patients, while less metabolically abnormal, had a similar risk for fibrosis progression as obese patients. Obesity status did not impact the efficiency of antiviral therapy.

C-C chemokine receptor 5 is essential for conventional NK cell trafficking and liver injury in a murine hepatitis virus-induced fulminant hepatic failure model.

BACKGROUND: Previous studies have demonstrated that natural killer (NK) cells migrated into the liver from peripheral organs and exerted cytotoxic effects on hepatocytes in virus-induced liver failure. AIM: This study aimed to investigate the potential therapeutic role of chemokine receptors in the migration of NK cells in a murine hepatitis  virus strain 3 (MHV-3)-induced fulminant hepatic failure (MHV-3-FHF) model and its mechanism. RESULTS: By gene array analysis, chemokine (C-C motif) receptor 5 (CCR5) was found to have remarkably elevated expression levels in hepatic NK cells after MHV-3 infection. The number of hepatic CCR5+ conventional NK (cNK) cells increased and peaked at 48 h after MHV-3 infection, while the number of hepatic resident NK (rNK) cells steadily declined. Moreover, the expression of CCR5-related chemokines, including macrophage inflammatory protein (MIP)-1α, MIP-1ß and regulated on activation, normal T-cell expressed and secreted (RANTES) was significantly upregulated in MHV-3-infected hepatocytes. In an in vitro Transwell migration assay, CCR5-blocked splenic cNK cells showed decreased migration towards MHV-3-infected hepatocytes, and inhibition of MIP-1ß or RANTES but not MIP-1α decreased cNK cell migration. Moreover, CCR5 knockout (KO) mice displayed reduced infiltration of hepatic cNK cells after MHV-3 infection, accompanied by attenuated liver injury and improved mouse survival time. Adoptive transfer of cNK cells from wild-type mice into CCR5 KO mice resulted in the abundant accumulation of hepatic cNK cells and aggravated liver injury. Moreover, pharmacological inhibition of CCR5 by maraviroc reduced cNK cell infiltration in the liver and liver injury in the MHV-3-FHF model. CONCLUSION: The CCR5-MIP-1ß/RANTES axis played a critical role in the recruitment of cNK cells to the liver during MHV-3-induced liver injury. Targeted inhibition of CCR5 provides a therapeutic approach to ameliorate liver damage during virus-induced acute liver injury.

Establishment of Ferroptosis-Associated Molecular Subtypes and Hub Genes Related to the Immune Microenvironment of Heart Failure.

BACKGROUND: Ferroptosis is a form of iron-dependent regulated cell death, and prior work has highlighted the potential utility of ferroptosis-inducing agents as tools to treat heart failure (HF). To date, however, no detailed examinations of the prognostic utility of ferroptosis-related genes (FRGs) in HF have been conducted. METHODS: We used established genomic identification of FRGs for total samples in the gene expression omnibus (GEO) database, screened for differentially expressed FRGs, performed protein-protein interaction analysis and functional analysis of HF immune microenvironment subtypes. Subsequently, we applied tools to calculate immune cell infiltration, compare immune cell, immune response genomic and HLA gene differences between subtypes, and perform candidate drug identification. Finally, preliminary in vivo validation of the screened central genes was performed in animal models. RESULTS: FRGs were compared between samples from HF and healthy control donors, revealing 62 of these genes to be differentially expressed as a function of HF status. HF patient-derived tissues exhibited significant changes in the expression of HLA genes, increase immune cell infiltration, and higher levels of other immune-related genes within the associated immune microenvironment. These FRGs were then leveraged to establish two different immune-related subtypes of HF based on clustering analysis results, after which these subtypes were characterized in further detail. Functional enrichment analyses revealed the identified differentially expressed genes to be enriched in key immune-related pathways including the primary immunodeficiency, natural killer cell-mediated cytotoxicity, FcϵRI signaling, and antigen processing and presentation pathways. The impact of the immune microenvironment was also explored through functional analyses, core gene analyses, and efforts to identify potential drug candidates for HF patients. Moreover, four key hub genes were identified as promising targets for therapeutic intervention in HF, including HDAC1, LNPEP, PSMA1, and PSMA6. Subsequent preclinical work in a mouse model system supported a potential role for HDAC1 as an important biomarker associated with the incidence of HF. CONCLUSIONS: To sum up, these results emphasize the importance of ferroptosis as a regulator of the HF-related immune microenvironment, highlighting viable avenues for the further study of molecular targets amenable to pharmacological intervention with the aim of treating this debilitating disease.

The clinical research on the effect of hydrogen-rich water on primary retinitis pigmentosa.

Objective: To investigate the feasibility and effectiveness of hydrogen in the treatment of retinitis pigmentosa (RP) patients through the drinking of hydrogen-rich water (HRW). Methods: RP patients clinically diagnosed in our hospital were selected and given HRW for drinking at 400-500 ml twice a day for four consecutive weeks. Changes in best corrected visual acuity (BCVA), intraocular pressure, the retinal thickness, and choroidal thickness, as well as the amplitude and peak time of visual electrophysiological examinations before and after HRW drinking were observed. Data were statistically analyzed. Results: In total, 24 eyes of 13 patients with RP (3 males and 10 females aged-27-65 years old, were enrolled in the study. The BCVA after HRW drinking was 0.34 ± 0.25, which was statistically improved compared with that before (P < 0.05). There were no significant differences in intraocular pressure, retinal lhickness, or choroidal thickness before and after HRW drinking (all P > 0.05). The amplitudes of the b-wave in Dark-adaptation 0.01 response, a and b waves in Dark-adaptation 3.0 response, the Dark-adaptation Ops total wave, a and b waves in Light-adaptation 3.0 response, and the Light-adaptation Flicker response of electroretinogram (ERG) were significantly higher than those before HRW drinking (all P < 0.05). The corresponding peak times iwere mproved to some extent compared to those before HRW consumption (all P < 0.05). Six patients with RP (11 eyes) had a BCVAm ore than 20/200. The amplitude and peak time of the P100 -ave from the 1°p attern visual evoked potentials (PVEP) were not significantly different from those before HRW drinking (P > 0.05), while the data from the 15' PVEP were statistically different (P < 0.05). Seven patients with RP (13 eyes) had a BCVA less than. 20/200 No significant differences were found in the amplitude and peak time of the P2 wave from the 1.0 Hz flash visual evoked potentials (FVEP) and the amplitude from the 12 Hz FVEP compared with those before HRW drinking (all P > 0.05). Conclusion: Short-term HRW drinking slightly improved visual function in patients with primary RP, whereas no significant improvement was found in the thickness of the retina and choroid.

Anti-VEGF combined with ocular corticosteroids therapy versus anti-VEGF monotherapy for diabetic macular edema focusing on drugs injection times and confounding factors of pseudophakic eyes: A systematic review and meta-analysis.

PURPOSE: To assess the effectiveness and safety of combining intravitreal endothelial growth factor inhibitor (anti-VEGF) and ocular corticosteroids for diabetic macular edema (DME). METHODS: Articles concentrating on the efficacy and safety of combining anti-VEGF and ocular corticosteroids therapy for DME versus anti-VEGF monotherapy was screened systematically. Meta-analysis was conducted on the basis of a protocol registered in the PROSPERO (CRD42023408338) and performed on the extracted continuous variables and dichotomous variables. The outcome was expressed as weighted mean difference (MD) and risk ratio (RR). RESULTS: Add up to 21 studies including 1468 eyes were enrolled in this study. The MD for best-corrected visual acuity (BCVA) improvement at 1/3/6/12-month between the combination therapy group and monotherapy group were 2.56 (95% CI [0.43, 4.70]), 2.46 (95% CI [-0.40, 5.32]), - 1.76 (95% CI [-3.18, -0.34]), - 1.94 (95% CI [-3.87, 0.00]), respectively. The MD for central retinal thickness (CMT) reduction at 1/3/6/12-month between two groups were - 66.27 (95% CI [-101.08, -31.47]), - 33.62 (95% CI [-57.55, -9.70]), - 4.54 (95% CI [-16.84, 7.76]), - 26.67 (95% CI [-41.52, -11.82]), respectively. Additionally, the combination group had higher relative risk of high intraocular pressure and cataract progression events. CONCLUSIONS: Anti-VEGF combined with ocular corticosteroids had a significant advantage over anti-VEGF monotherapy within 3 months of DME treatment, which reached the maximum with increasing anti-VEGF injection times to 3. However, with the prolongation of the treatment cycle, the effect of combined therapy after 6 months was no better than monotherapy, and the side effects of combined therapy were more severe.

The association of the serum levels of aldehydes with diabetes-related eye diseases: a cross-sectional population-based study.

Diabetes could impact many ocular tissues. However, the association of the serum aldehydes with diabetes-related eye diseases (DED) remains unclear. Thus, we aimed to examine the above relationship from the general US population of 2013-2014 National Health and Nutrition Examination Survey (NHANES). The multivariable logistic regression and Bayesian kernel machine regression (BKMR) were used to analyze the effect of serum aldehydes on the risk of DED. Pearson's correlation analysis, the restricted cubic spline (RCS) model, and the linear regression were performed to explore the association between the serum aldehydes and other parameters. The multivariable linear regression was conducted to further underlie the relationship between the serum aldehydes and the glycohemoglobin A1c (HbA1c) in DED participants. Although no significant association was observed between the serum aldehydes and the risk of DED by the multivariable logistic regression and BKMR, the Pearson correlation revealed a positive association between the HbA1c level and the serum level of heptanaldehyde and isopentanaldehyde in DED participants. The RCS model confirmed the above linear correlation. After adjusting for the cofounding factor of smoking, the multivariable linear regression revealed a significant association between the serum level of heptanaldehyde and the HbA1c level in DED participants. Our results suggest that aldehyde exposure did not significantly increase the risk of DED, while heptanaldehyde was the risk factor for increased HbA1c in DED population.

Fibrinogen-like protein 2 regulates macrophage glycolytic reprogramming by directly targeting PKM2 and exacerbates alcoholic liver injury.

BACKGROUND & AIMS: Switching of the macrophage activation phenotype affects the pathogenesis of alcoholic liver diseases, and metabolic reprogramming can provide the energy demand for macrophage phenotypes shift. However, the molecular mechanism by which immune metabolism regulates the activation of proinflammatory macrophages remains unclear. APPROACH: Expression of Fgl2 was examined in patients with alcoholic hepatitis and healthy controls. Mice were fed with a Lieber-DeCarli diet. Livers from mice were used to observe liver injury and macrophage activation. Fgl2 overexpressing THP-1 cell was used to find interacting partners through immunoprecipitation plus mass spectrometry. Naive bone marrow derived macrophages stimulated with LPS and ethanol were used for cell experiments. RESULTS: Expression of Fgl2 was elevated in macrophages of livers from mice with chronic-binge ethanol feeding or patients with alcoholic hepatitis. Fgl2 depletion ameliorated ethanol diet-induced hepatic steatosis and oxidative injury as well as the levels of proinflammatory cytokines. Fgl2-/- mice exhibited suppressed M1 polarization and glycolysis pathway activation. Fgl2 interacted with the M2 isoform of pyruvate kinase (PKM2) in macrophages and facilitated PKM2 nuclear translocation, thus promoting glycolysis in M1 macrophages and the secretion of proinflammatory cytokines. Furthermore, Fgl2 overexpression in THP-1 cells enhances PKM2-dependent glycolysis and inflammation, which could be reversed by activation of enzymatic PKM2 using DASA58. CONCLUSIONS: Taken together, Fgl2 hastens the development of alcoholic liver injury by mediating PKM2 dependent aerobic glycolysis in proinflammatory macrophages. Strategies that inhibiting proinflammatory macrophage activation by silencing Fgl2 might be a potential therapeutic intervention for alcoholic liver injury.

Long-term SARS-CoV-2 neutralizing antibody level prediction using multimodal deep learning: A prospective cohort study on longitudinal data in Wuhan, China.

The ongoing epidemic of SARS-CoV-2 is taking a substantial financial and health toll on people worldwide. Assessing the level and duration of SARS-CoV-2 neutralizing antibody (Nab) would provide key information for government to make sound healthcare policies. Assessed at 3-, 6-, 12-, and 18-month postdischarge, we described the temporal change of IgG levels in 450 individuals with moderate to critical COVID-19 infection. Moreover, a data imputation framework combined with a novel deep learning model was implemented to predict the long-term Nab and IgG levels in these patients. Demographic characteristics, inspection reports, and CT scans during hospitalization were used in this model. Interpretability of the model was further validated with Shapely Additive exPlanation (SHAP) and Gradient-weighted Class Activation Mapping (GradCAM). IgG levels peaked at 3 months and remained stable in 12 months postdischarge, followed by a significant decline in 18 months postdischarge. However, the Nab levels declined from 6 months postdischarge. By training on the cohort of 450 patients, our long-term antibody prediction (LTAP) model could predict long-term IgG levels with relatively high area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score, which far exceeds the performance achievable by commonly used models. Several prognostic factors including FDP levels, the percentages of T cells, B cells and natural killer cells, older age, sex, underlying diseases, and so forth, served as important indicators for IgG prediction. Based on these top 15 prognostic factors identified in IgG prediction, a simplified LTAP model for Nab level prediction was established and achieved an AUC of 0.828, which was 8.9% higher than MLP and 6.6% higher than LSTM. The close correlation between IgG and Nab levels making it possible to predict long-term Nab levels based on the factors selected by our LTAP model. Furthermore, our model identified that coagulation disorders and excessive immune response, which indicate disease severity, are closely related to the production of IgG and Nab. This universal model can be used as routine discharge tests to identify virus-infected individuals at risk for recurrent infection and determine the optimal timing of vaccination for general populations.

The impacts of resveratrol on the retinal degeneration in a rat model of retinitis pigmentosa induced by alkylation: an in-vivo study.

Upregulation of Sirtuin Type 1 (SIRT1), a nicotinamide adeninedinucleotide (NAD+)-dependent deacetylase, has been proved to protect against ample ocular diseases, while its effect on retinitis pigmentosa (RP) has not been illustrated. The study was aimed to explore the impacts of resveratrol (RSV), a SIRT1 activator, on the photoreceptor degeneration in a rat model of RP induced by N-methyl-N-nitrosourea (MNU), an alkylation. The rats were induced RP phenotypes via the intraperitoneal injection of MNU. The electroretinogram was conducted and revealed that RSV could not prevent the decline of retinal function in the RP rats. The optical coherence tomography (OCT) and the retinal histological examination were performed and showed that the reduced thickness of the outer nuclear layer (ONL) was not preserved by RSV intervention. The immunostaining technique was applied. Afther the MNU administration, the number of the apoptotic photoreceptors in the ONL throughout the retinasand the number of microglia cells present among the outer part throughout the retinas were not significantly reduced by RSV. Western blotting was also performed. The data showed that the level of SIRT1 protein was decreased after MNU administration, while RSV was not able to obviously alleviate the downregulation. Our data together indicated that RSV was not able to rescue the photoreceptor degeneration in the MNU-induced RP rats, which might be due to the MNU-induced consumption of the NAD+.

Pharmacological roles of lncRNAs in diabetic retinopathy with a focus on oxidative stress and inflammation.

Diabetic retinopathy (DR) is a complication caused by abnormal glucose metabolism, which affects the vision and quality of life of patients and severely impacts the society at large.DR has a complex pathogenic process. Evidence from multiple studies have shown that oxidative stress and inflammation play pivotal roles in DR.Additionally, with the rapid development of various genetic detection methods, the abnormal expression of long non-coding RNAs (lncRNAs) have been confirmed to promote the development of DR.Research has demonstrated the potential of lncRNAs as ideal biomarkers and theranostic targets in DR. In this narrative review, we will focus on the research results on mechanisms underlying DR, list lncRNAs confirmed to be closely related to these mechanisms, and discuss their potential clinical application value and limitations.

Fibrinogen-like protein 2 promotes proinflammatory macrophage polarization and mitochondrial dysfunction in liver fibrosis.

Fibrinogen-like protein 2 (Fgl2) robustly activates macrophages in response to infection or inflammatory cytokine challenge and is markedly increased in the liver tissues of liver cirrhosis patientswithhepatitisCvirus(HCV) infection. However, the molecular mechanism underlying the involvement of Fgl2 in macrophage function in the pathogenesis of liver fibrosis remains unclear. In this study, we demonstrated that increased hepatic Fgl2 expression was associated with hepatic inflammation and high-grade liver fibrosis in patients with hepatitis B virus (HBV) infection and experimental models. Genetic ablation of Fgl2 alleviated hepatic inflammation and fibrosis progression. Fgl2 promoted M1 macrophage polarization and increased the production of proinflammatory cytokines that contribute to inflammatory damage and fibrosis development. In addition, Fgl2 augmented mitochondrial reactive oxygen species (ROS) production and modulated mitochondrial functions. Fgl2-mediated mtROS were involved in macrophage activation and polarization. We further demonstrated that in macrophages, Fgl2 localized to not only the cytosol but also mitochondria, where it bound to cytosolic and mitochondrial heat shock protein 90 (HSP90). Mechanistically, Fgl2 interacted with HSP90, hindering the interaction of HSP90 with its target protein Akt, significantly inhibiting Akt phosphorylation and downstream FoxO1 phosphorylation. These results reveal different layers of regulation of Fgl2 that are necessary for inflammatory damage and mitochondrial dysfunction in M1-polarized macrophages. Therefore, Fgl2 may be a potent target in liver fibrosis treatment.

Inhibitors mitigate N2O emissions more effectively than biochar: A global perspective.

Farmlands receive large amounts of nitrogen (N) from anthropogenic activities, which increase N2O emissions and promote crop productivity. Inhibitor or biochar applications have proven effective in reducing N2O emissions and promoting crop yields worldwide. However, a direct comparison of the response of N2O emissions and crop yields to inhibitor and biochar applications has not been performed. Here, we conducted a meta-analysis of 787 datasets from different locations worldwide to investigate the response of N2O emissions and crop yields to inhibitor or biochar applications for different climate factors and experimental conditions and determine the key influencing factors. We found that inhibitor applications (37.4 %) resulted in larger N2O emission reductions than biochar applications (20.2 %), but there was no difference in the crop yield improvement (5.8 % and 5.4 %, respectively). Nitrification inhibitor (NI) applications reduced N2O emissions by 40.8 %, a larger reduction than that of urease inhibitor (UI) applications (24.3 %) and the combination of NI and UI applications (36.4 %); 3,4-dimethylpyrazole succinic (DMPSA) was the most effective NI in reducing N2O emissions (50.7 %). We also found that NI applications were more effective in reducing N2O emissions than biochar applications in different climates and experimental conditions (N source, N rate, cropland type, and soil texture). In addition, the N rate was the most important factor impacting N2O emissions and crop yields when inhibitors were applied, whereas the experimental duration had the largest influence on N2O emissions under biochar applications. Moreover, soil factors were also related to N2O emissions under biochar applications or inhibitor applications. Our findings indicate that inhibitors are more effective in reducing N2O emissions than biochar worldwide.

Effect of molecular hydrogen, a novelly-established antioxidant, on the retinal degeneration of hereditary retinitis pigmentosa: an in-vivo study.

Objective Our research was performed in order to explore the effects of molecular hydrogen (H2), a novelly-established antioxidant, on the retinal degeneration in rd1 mice, an animal model of inherited retinitis pigmentosa (RP). Methods The rd1 mice were divided randomly into control and H2 intervention groups. Mice from other groups received H2 intervention in three modes, two modes of the hydrogen gas (HG) and one model of hydrogen-rich saline (HRS). At 14 days post born (P14) and P21, various indicators were detected in all mice, including eletroretinogram (ERG), fundus phography, optical coherence tomography (OCT), and retinal immunotaining of microglia cells' marker, Iba1. Results The ERG amplitude in mice from the control and H2 intervention groups showed no statistical differences (p > 0.05). At P14 and P21, no significant difference in the distance from the retinal pigment epithelium to the outer plexiform layer on OCT from mice of the above two groups was found (p > 0.05). The thickness of the outer nuclear layer (ONL) in mice at P14 and P21 showed no statistical differences between the control group and the H2 intervention group (p > 0.05). In the aspect of the number of Iba1-positive cells, we did not found any significant differences between the two groups (p > 0.05). Conclusion Different forms of H2 intervention (hydrogen-rich saline and hydrogen gas) had no obvious effects on the course of retinal degeneration in rd1 mice. The specific mechanism of photoreceptor degeneration in the hereditary RP mouse model may be different, requiring different medical interventions.

The prevalence of ocular Demodex folliculorum in 2253 young males.

To investigate the prevalence and influencing factors of Demodex folliculorum (DF) in the eyelashes of healthy young males. An epidemiological cross-sectional prevalence study was conducted. We conducted visual acuity, eye-related examination, eyelash microscopic examination and DF count of recruits in Fujian Province in 2019. The presence of DF was analyzed according to age, keratorefractive surgery, annual household income, educational level, long-term residence, sleep time, time of using electronic products, smoking and drinking habit. A total of 2253 healthy young males (aged 17-24 years) were studied for the presence of DF within eyelash follicles. The total prevalence of DF was 20.73% in our study. Subjects with history of keratorefractive surgery had a statistically significant increase in the prevalence of DF (P < 0.001). The prevalence of DF was higher in subjects with ocular symptoms than in those without symptoms (P < 0.05). Factors such as the educational level and so on we analyzed had no significant correlation with the prevalence of DF (all P > 0.05). According to the multivariate logistic regression analysis, the history of keratorefractive surgery was the risk factors of DF infection (P < 0.001), and the risk of infection was 1.437 times higher in the population with the history of keratorefractive surgery than in the population without. There was no correlation between ocular discomfort and DF infection (P > 0.05). The prevalence of DF in eyelash follicles in healthy young males was relatively high. The history of keratorefractive surgery was an important risk factor for the infection.