Mitochondrial dysfunction and NLRP3 inflammasome: key players in kidney stone formation.

The mitochondrion serves as a critical intracellular organelle, engaging in essential roles in the regulation of energy production, oxidative stress management, calcium homeostasis, and apoptosis. One such disease that has been particularly associated with these functions is kidney stone disease (KSD), specifically calcium oxalate (CaOx). It is underpinned by oxidative stress and tissue inflammation. Recent studies have shed light on the vital involvement of mitochondrial dysfunction, the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome, endoplasmic reticulum stress and subsequent cell death in CaOx crystal retention and aggregation. These processes are pivotal in the pathogenesis of kidney stone formation. This review focuses on the pivotal roles of mitochondria in renal cell functions and provides an overview of the intricate interconnectedness between mitochondrial dysfunction and NLRP3 inflammasome activation in the context of KSD. It is essential to recognise the utmost significance of gaining a comprehensive understanding of the mechanisms that safeguard mitochondrial function and regulate the NLRP3 inflammasome. Such knowledge carries significant scientific implications and opens up promising avenues for the development of innovative strategies to prevent the formation of kidney stones.

HIF-1α aggravates pathologic myopia through the miR-150-5p/LAMA4/p38 MAPK signaling axis.

Therapeutic inhibition of hypoxia-inducible factor-1alpha (HIF-1α) action has emerged as a potential approach for managing several diseases, including myopia. Herein, we analyzed the role of HIF-1α in the progression of pathologic myopia by regulating the miR-150-5p/LAMA4/p38 MAPK axis. Microarray-based gene expression profiling of pathologic myopia was employed to identify differentially expressed genes. Human scleral fibroblasts (HSFs) were cultured under the hypoxic conditions. Interaction among HIF-1α, miR-150-5p, and LAMA4 was identified. Gain- and loss-of-function experiments were performed in hypoxia-exposed HSFs to evaluate the effect of the HIF-1α/miR-150-5p/LAMA4/p38 MAPK axis on the extracellular matrix (ECM) degradation of HSFs and the subsequent pathologic myopia progression. Increased LAMA4 but decreased miR-150-5p was found in serum sample of pathologic myopia patients. HIF-1α and LAMA4 were abundantly expressed, and p38 MAPK was activated while miR-150-5p was weakly expressed in hypoxia-exposed HSFs. HIF-1α was enriched in the promoter region of miR-150-5p and downregulated its expression, thus repressing the ECM degradation of HSFs as shown by increased COL1A1 and TIMP-2 and reduced MMP2. In addition, LAMA4 was a downstream target of miR-150-5p and under the negative regulation by miR-150-5p. Overexpression of miR-150-5p promoted the ECM degradation of HSFs by inhibiting LAMA4 expression and p38 MAPK signaling pathway. However, upregulation of LAMA4 reversed the promoting effect of miR-150-5p on ECM degradation of HSFs. Overall, our findings suggest that HIF-1α can decline miR-150-5p expression and facilitate LAMA4-mediated p38 MAPK signaling pathway activation, thus arresting ECM degradation of HSFs and eventually inducing pathologic myopia.

[Research advances in drug resistance of Aeromonas hydrophila in fishery].

As one of the most common pathogens in aquatic animals, Aeromonas hydrophila exhibits a wide range of pathogenicity. Due to factors like unreasonable use of antibiotics and horizontal gene transfer mediated by plasmids, many resistant strains of Aeromonas hydrophila were isolated from ready-to-eat seafood products in retail markets, supermarkets and restaurants. These strains carry many resistance genes. Therefore, it is essential to explore the key control points, and seek for prevention and control strategies so as to effectively alleviate antibiotic resistance. We review here the prevalence of drug resistance of Aeromonas hydrophila in China, and its main infection and resistance mechanisms, and the main means and strategies for reducing and preventing drug resistance. We also address further research directions and focus on drug resistance in Aeromonas hydrophila of the aquatic product.

Down-regulated LAMA4 inhibits oxidative stress-induced apoptosis of retinal ganglion cells through the MAPK signaling pathway in rats with glaucoma.

Glaucoma is a neurodegenerative disorder that is generally accepted as the main cause of vision loss. In this study, we tested the hypothesis that laminin α4 (LAMA4) is implicated in glaucoma development by controlling apoptosis of retinal ganglion cells (RGCs) through the mitogen-activated protein kinase (MAPK) signaling pathway. Expression profiles and genes associated with glaucoma were searched to determine the objective gene. Intraocular pressure (IOP) rats model were established and IOP was measured. The mRNA and protein expression of LAMA4, JNK, p38 MAPK, ERK, Bcl-2, Bax, Caspase-9, and p53 was determined in concert with the treatment of H2O2, si-NC, or si-LAMA4 in cultured RGCs. Viability of RGCs, reactive oxygen species (ROS) and cell apoptosis was also measured. LAMA4 was selected as the study object because of its significant difference in two expression profiles. IOP of rats with glaucoma increased significantly after model establishment, and the LAMA4 protein expression in retinal tissue of rats with glaucoma was elevated. Down-regulation of LAMA4 could inhibit the mRNA and protein expression of LAMA4, JNK, p38 MAPK, ERK, Bax, Caspase-9, and p53, as well as restrain the apoptosis and ROS of RGCs, but improve Bcl-2 expression and viability of RGCs. Collectively, the obtained data supported that downregulated LAMA4 might reduce the oxidative stress-induced apoptosis of glaucoma RGCs by inhibiting the activation of the MAPK signaling pathway.

Clinical features of chinese patients with Behçet's disease.

PURPOSE: To characterize the clinical features of Behçet's disease in Chinese patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Seven hundred seventy-five eyes of 437 patients with Behçet's disease initially examined from August, 1995, through June, 2006. METHODS: The history, demographic parameters, and clinical findings of all consecutive Behçet's patients referred to the uveitis study center of Sun Yat-sen University were reviewed. Laser flare-cell photometry (LFCM), fundus fluorescein angiography (FFA), optical coherence tomography (OCT), ultrasound biomicroscopy (UBM), and B-scan ultrasonography were performed in certain cases. Most patients were treated by immunosuppressive agents combined with oral corticosteroids. MAIN OUTCOME MEASURES: Patient demographics, clinical presentation, and auxiliary examination findings. RESULTS: Four hundred thirty-seven patients were diagnosed with Behçet's disease. There were 319 male and 118 female patients. Panuveitis was the most common type of uveitis in both genders, although anterior uveitis was seen more frequently in females. Retinal vasculitis, vitreitis, and retinitis were the most common ocular manifestations in these patients. Cataract and macular edema were the most common complications. Oral aphthae were the most frequent extraocular manifestation, followed by dermatologic lesions, and genital ulcers. The results of FFA, OCT, B-scan ultrasonography, LFCM, and UBM generally were in accordance with or comparable with clinical observations. At the final visit, uveitis was well controlled in 86.2% of patients. However, 20.4% of eyes became legally blind despite aggressive treatment. Kaplan-Meier analysis estimated the risk of losing useful vision (0.05) at 5 and 10 years for males and females as 29% versus 6% and 65% versus 33%, respectively. CONCLUSIONS: Behçet's disease in Chinese patients mainly manifests as nongranulomatous uveitis frequently associated with oral aphthae and dermatologic lesions. Fundus fluorescein angiography, B-scan ultrasonography, LFCM, UBM, and OCT may provide much information about pathophysiologic hallmarks of Behçet's disease. A combination of corticosteroids with other immunosuppressive agents is effective for most patients with Behçet's disease. Males had a more severe course and were at higher risk for losing vision than females.

Clinical characteristics of Vogt-Koyanagi-Harada syndrome in Chinese patients.

PURPOSE: To characterize the clinical features of Vogt-Koyanagi-Harada syndrome (VKH) in Chinese patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: A total of 410 consecutive VKH patients examined from August 1995 to April 2005. METHODS: Charts of these patients were reviewed according to international VKH criteria. Patients who consulted us within 2 weeks after a uveitis attack were classified into group 1; between 2 weeks and 2 months into group 2; and after 2 months into group 3. The history and clinical findings of all of the patients were reviewed. Laser flare-cell photometry, fundus fluorescein angiography, indocyanine green angiography, optical coherence tomography, B-scan ultrasonography, and ultrasound biomicroscopy were performed in certain cases. Corticosteroids were mainly used to treat patients in groups 1 and 2, whereas cyclosporine or chlorambucil in combination with corticosteroids were prescribed for patients in group 3. MAIN OUTCOME MEASURES: Demographics, clinical presentation, and ancillary examinations of the patients in all 3 groups. RESULTS: The patients were diagnosed as having either complete (n = 273), incomplete (n = 76), or probable (n = 61) VKH syndrome. Exudative retinal detachment and either choroiditis or chorioretinitis were the main findings in group 1. Posterior uveitis with mild to moderate anterior uveitis simulating a nongranulomatous inflammation as evidenced by dust keratic precipitates, anterior chamber cells, and flare was noted in group 2. Recurrent granulomatous anterior uveitis with a "sunset glow" fundus was observed in group 3. Complicated cataract was the most common complication in the patients in group 3. At the final visit, the uveitis was completely controlled in all patients and a best-corrected visual acuity of <20/200 was 1.9%/eye-year, 1.2%/eye-year, and 6%/eye-year in groups 1, 2, and 3, respectively. CONCLUSION: Vogt-Koyanagi-Harada syndrome in Chinese patients is characterized by early posterior uveitis, and if the syndrome is not controlled, subsequent recurrent granulomatous anterior uveitis. Good visual prognosis is possible if the patients are managed according to a tailored immunosuppressive treatment protocol.

CD4+PD-1+ T cells acting as regulatory cells during the induction of anterior chamber-associated immune deviation.

PURPOSE: To study the expression and functional characteristics of programmed death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber-associated immune deviation (ACAID). METHODS: ACAID was induced in BALB/c mice by intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands in the spleens of ACAID mice was determined by quantitative real-time PCR, Western blotting, and flow cytometry. In vitro proliferation assays, enzyme-linked immunosorbent assays, and adoptive transfer assays were used to investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID mice. RESULTS: Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were able to significantly inhibit the antigen-specific, delayed-type hypersensitivity response when adoptively transferred to naive mice. CONCLUSIONS: CD4+PD-1+ T cells from ACAID mice, as regulatory cells, are involved in the induction of antigen-specific suppression in association with enhanced expression of IL-10. CD4+PD-1+ T cells in the murine spleen may represent a substantial population of regulatory T cells possibly responsible for the induction of ACAID after intracameral injection of antigen.

OVA-specific CD8+ T cells do not express granzyme B during anterior chamber associated immune deviation.

PURPOSE: To examine antigen (Ag)-specific CTL response during anterior chamber associated immune deviation (ACAID). METHODS: OVA or OVA257-264 peptide was injected into the anterior chamber (AC) of C57BL/6 mice. There were 16 mice in each ACAID group induced with OVA or OVA257-264 peptide. The mice were primed by SC injection with OVA or OVA 257-264 peptide in complete Freund's adjuvant (CFA) on day 7. Ag-specific CD8+ T cells in spleens were analyzed on day 14 using Pentamer H-2K(b)-SIINFEKL(OVA257-264 peptide). IFN-gamma ELISPOT and intracellular granzyme B staining were used to characterize the CTL response. Twelve mice in each group immunized with OVA or OVA257-264 peptide in CFA served as positive controls. Twelve normal mice served as negative controls and 12 receiving injection of CFA as CFA controls for studying the influence of CFA on the Ag-specific CTL response. RESULT: The results showed that anterior chamber inoculation of OVA or OVA257-264 peptide could induce ACAID as evidenced by an impaired DTH response. The frequency of Ag-specific CD8+ T cells in ACAID mice was not different from that in mice challenged with Ags in CFA only (positive controls). IFN-gamma production by these cells in ACAID mice was not different compared to positive controls. However, Ag-specific CD8+ T cells in ACAID mice failed to secrete granzyme B. Mice challenged only with OVA peptide and CFA also showed a granzyme B negative CD8+ T cell response. Ag-specific CTL response induced by CFA alone was similar with the negative control. CONCLUSION: These results show that the frequency of Ag-specific CD8+ T cells is not altered during ACAID. The Ag-specific CTL response during ACAID is characterized by the absence of granzyme B expression.

Clinical patterns and characteristics of uveitis in a tertiary center for uveitis in China.

PURPOSE: To address the clinical pattern and characteristics of uveitis in a tertiary center for uveitis in China and compare the similarity and difference in the distribution of uveitis entities between China and other countries. METHODS: A retrospective study was performed on the patients with uveitis referred to the Zhongshan Ophthalmic Center from January 1996 to December 2003. The clinical data including category, etiology, gender, and the age of the patients at uveitis presentation were analyzed and compared with studies published previously from other countries. RESULTS: There were 902 male and 850 female patients in our series. The mean age of these patients at uveitis presentation was 33.8 +/- 16.5 years. Anterior uveitis (800, 45.6%) was the most common anatomical entity, followed by panuveitis (727, 41.5%), posterior uveitis (119, 6.8%), and intermediate uveitis (106, 6.1%). Further classification with the etiology criteria revealed 16 entities in anterior uveitis, with idiopathic anterior uveitis being the most common entity (473, 27.0%). Twelve entities were identified in panuveitis, of which Behçet disease (289, 16.5%) and Vogt-Koyanagi-Harada (VKH) syndrome (278, 15.9%) were the predominant ones. No specific entity was recognized in the intermediate uveitis group. Although a number of specific entities were identified in posterior uveitis, toxoplasmosis was noted in only two patients in this group. CONCLUSIONS: Idiopathic anterior uveitis, Behçet disease, and VKH syndrome are the most common entities of uveitis in China. Ocular toxoplasmosis, ocular histoplasmosis, and birdshot retinochoroidopathy are less common or absent in China.