Astaxanthin protects against MPP+-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis

BACKGROUND: Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. NOX2, a cytochrome subunit of NOX, transports electrons across the plasma membrane to generate ROS, leading to physiological and pathological processes. Heme oxygenase-1 (HO-1) can be rapidly induced by oxidative stress and other noxious stimuli in the brain or other tissues. Astaxanthin (ATX), a carotenoid with antioxidant properties, is 100–1000 times more effective than vitamin E. The present study investigated the neuroprotective effects of ATX on MPP(+)-induced oxidative stress in PC12 cells. RESULTS: MPP(+) significantly decreased MTT levels in a concentration-dependent manner. Hemin, SnPPIX and ATX didn’t exhibit any cytotoxic effects on PC12 cells. Pretreatment with ATX (5, 10, 20 μM), caused intracellular ROS production in the MPP(+) group to decrease by 13.06%, 22.13%, and 27.86%, respectively. MPP(+) increased NOX2, NRF2 and HO-1 protein expression compared with control (p < 0.05). Co-treatment with hemin or ATX suppressed NOX2 expression (p < 0.01), and greatly increased NRF2 and HO-1 expression (p < 0.01). MPP(+) treatment up-regulated both NOX2 (p < 0.01) and HO-1 (p < 0.01) mRNA levels. Co-treatment with hemin or ATX significantly increased HO-1 mRNA levels (p < 0.01), and decreased NOX2 mRNA levels (p < 0.01). MPP(+) increased NOX2 and HO-1 expression with considerable fluorescence extending out from the perinuclear region toward the periphery; this was attenuated by DPI. Co-treatment with hemin or ATX significantly up-regulated HO-1 expression and decreased NOX2 expression with considerable fluorescence intensity (stronger than the control and MPP(+) groups). CONCLUSIONS: ATX suppresses MPP(+)-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis. ATX should be strongly considered as a potential neuroprotectant and adjuvant therapy for patients with Parkinson’s disease

Serum uromodulin and progression of kidney disease in patients with chronic kidney disease

Abstract Background Uromodulin is specifically synthesized and secreted by kidney tubular epithelial cells. Studies on the association of serum uromodulin and outcomes of chronic kidney disease (CKD) are lacking. This study aimed to evaluate whether serum uromodulin was associated with outcomes of patients with CKD. Methods We measured serum uromodulin concentrations by ELISA in 2652 CKD patients from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) and investigated the association of serum uromodulin with outcomes of CKD patients, including end-stage kidney disease (ESKD) receiving kidney replacement therapy, cardiovascular events and mortality by Cox proportional hazards regression model. Results A total of 2652 CKD patients were enrolled in this study, with an age of 48.7 ± 13.8 years and the baseline eGFR of 49.6 ± 29.4 mL/min/1.73 m2, of whom 58.4% were male. The median level of urinary albumin/creatinine ratio and serum uromodulin was 473.7 mg/g (IQR 134.1–1046.6 mg/g) and 77.2 ng/mL (IQR 48.3–125.9 ng/mL), respectively. Altogether, 404 ESKD, 189 cardiovascular events, and 69 deaths occurred during the median follow-up of 53.6 (IQR 44.0–64.0) months. Lower levels of serum uromodulin were independently associated with higher risk of incident ESKD after adjusting for traditional cardiovascular risk factors, with the hazard ratios (HRs) of 3.23 (95% confidence intervals [CIs] 2.15–4.85) for the middle tertile and 7.47 (95% CI 5.06–11.03) for the bottom tertile, compared with top tertile and 0.31 (95% CI 0.25–0.38) per every standard deviation increase. After further adjustment for the baseline eGFR, the association was greatly attenuated, but still significant, with HRs of 1.92 (95% CI 1.26–2.90) for the bottom tertile compared with top tertile and 0.69 (95% CI 0.55–0.86) per every standard deviation increase. Conclusions Serum uromodulin is independently associated with an increased risk of incident ESKD in CKD patients.https://deepblue.lib.umich.edu/bitstream/2027.42/146520/1/12967_2018_Article_1693.pd

High pO2 Floating Zone Crystal Growth of the Perovskite Nickelate PrNiO3

Single crystals of PrNiO3 were grown under an oxygen pressure of 295 bar using a unique high-pressure optical-image floating zone furnace. The crystals, with volume in excess of 1 mm3, were characterized structurally using single crystal and powder X-ray diffraction. Resistivity, specific heat, and magnetic susceptibility were measured, all of which evidenced an abrupt, first order metal-insulator transition (MIT) at ~130 K, in agreement with previous literature reports on polycrystalline specimens. Temperature-dependent single crystal diffraction was performed to investigate changes through the MIT. Our study demonstrates the opportunity space for high fugacity, reactive environments for single crystal growth specifically of perovskite nickelates but more generally to correlated electron oxides.Comment: 19 pages, 6 figures, Supporting Information include

Investigation of He’s Yang Chao recipe against oxidative stress-related mitophagy and pyroptosis to improve ovarian function

BackgroundPrimary ovarian insufficiency (POI) is a common gynecological disease with serious ramifications including low pregnancy rate and low estrogen symptoms. Traditional Chinese medicine is regarded as an effective treatment for POI. However, the therapeutic mechanism of it is unclear.MethodsIn this study, a mouse model of primary ovarian insufficiency was established by intraperitoneal injection of cyclophosphamide (CTX) and He’s Yang Chao Recipe (HSYC) concentrate was used for intragastric administration. Serum hormone levels (Anti-Müllerian Hormone, Estradiol, Progesterone, Luteinizing Hormone and Follicle Stimulating Hormone) and Oxidative Stress (OS) related products, superoxide dismutase (SOD), GSH-Px, and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Pathological changes in ovarian tissue were evaluated by hematoxylin and eosin staining, and flow cytometry was used to determine reactive oxygen species content and mitochondrial membrane potential levels in granulosa cells. Mitochondrial distribution and morphology were investigated using immunofluorescence staining. The level of mitophagy was evaluated by LC3 immunofluorescence staining and autophagosome counts using electron microscopy. Western blotting and qPCR were used to detect the expression of proteins and genes related to mitophagy and the NLRP3 inflammasome.ResultsAfter HSYC treatment, the ovarian damage was milder than in the CTX group. Compared with the CTX group; SOD, GSH-Px, and the total antioxidant capacity were significantly increased, while MDA and ROS were decreased in the HSYC treatment groups. Furthermore, mitochondrial distribution and membrane potential levels were improved after HSYC treatment compared to the CTX group. After the HSYC treatment, the LC3 fluorescent intensity and autophagosome counts were decreased. Similarly, mitophagy related markers PINK1, Parkin, LC3, and Beclin1 were decreased, while p62 was significantly increased, compared with the CTX groups. The mRNA and protein expression of NLRP3 inflammasome, NLRP3, caspase-1, GSDMD, IL-18, and IL-1β were significantly decreased in the HSYC treatment groups.ConclusionThis is the first study in molecular mechanisms underlying HSYC against granulosa cell injury in POI. HSYC protects ovaries from CTX-induced ovarian damage and oxidative stress. HSYC enhanced ovarian function in mice with primary ovarian insufficiency by inhibiting PINK1-Parkin mitophagy and NLRP3 inflammasome activation

A decade of complex fractionated electrograms catheter-based ablation for atrial fibrillation: Literature analysis, meta-analysis and systematic review

AbstractBackgroundIt has been a decade since the complex fractionated atrial electrograms (CFAEs) were first established following the publication of Nademanee's standards. However, the status and focus of CFAE research are unclear, as is the efficacy of additional CFAE ablation in atrial fibrillation (AF). This literature review and meta-analysis were designed to determine the status of CFAE research and the efficacy and complications of CFAE ablation alone, pulmonary vein isolation (PVI) alone and PVI plus CFAE ablation in AF.MethodsWith the assistance from reference librarians and investigators trained in systematic review, we conducted a literature search of MEDLINE (via PubMed), Embase, the Cochrane Library, ScienceDirect, Wiley Blackwell and Web of Knowledge, using “complex fractionated atrial electrograms” for MeSH and keyword search.ResultsThe literature on CFAEs increased from 2007, mainly focusing on mapping studies, with mechanism studies increasing significantly from 2012. Fifteen trials with 1525 patients were qualified for our meta-analysis. Success rates were as follows. Overall (P < 0.001): CFAE ablation alone, 23.5–26.2%; PVI, 64.7%; PVI plus CFAE ablation, 67.0%. Single ablation: PVI, 60.4%; PVI plus CFAEs, 68.8% (OR 1.53, 95% CI 1.07–2.20, P = 0.02). Re-ablation: PVI, 69.0%; PVI plus CFAEs, 77.2% (OR 1.54, 95% CI 1.06–2.24, P = 0.02). Paroxysmal AF: PVI, 76.7%; PVI plus CFAEs, 79.1% (OR 1.20, 95% CI 0.79–1.81, P = 0.39). Persistent or permanent AF: PVI, 47.9%; PVI plus CFAEs, 58.7% (OR = 1.59, 95% CI 1.13–2.24, P = 0.008). Complication rates: PVI, 2.6%; PVI plus CFAEs, 3.4% (OR 1.22, 95% CI 0.58–2.57, P = 0.61).ConclusionsIn the literature, CFAE mapping studies preceded mechanism studies. CFAE ablation alone is insufficient for the treatment of AF. Additional CFAE ablation after adequate PVI or PVI plus linear ablation improves the outcome of single ablation and re-ablation without increasing complications, especially in persistent or permanent AF. There are insufficient data to support a similar improvement in paroxysmal AF or inducible AF after PVI for paroxysmal AF

Case report: Rare novel MIPEP compound heterozygous variants presenting with hypertrophic cardiomyopathy, severe lactic acidosis and hypotonia in a Chinese infant

BackgroundMitochondrial intermediate peptidase, encoded by the MIPEP gene, is involved in the processing of precursor mitochondrial proteins related to oxidative phosphorylation. Only a few studies have shown that mutations in MIPEP can cause combined oxidative phosphorylation deficiency-31 (COXPD31), an autosomal recessive multisystem disorder associated with mitochondrial dysfunction. We report herein a rare case of an 8-month-old boy in China with hypertrophic cardiomyopathy (HCM), severe lactic acidosis, and hypotonia caused by novel MIPEP compound heterozygous variants.MethodsTrio-whole-exome sequencing and copy number variation sequencing were performed to identify mutated genetic loci. Sanger sequencing and quantitative real-time PCR were used to validate the candidate single nucleotide variants and copy number variants, respectively.ResultsThe proband was an 8-month-old boy with HCM, severe lactic acidosis, and hypotonia who died 2 months after his first admission. Two novel compound heterozygous variants, c.1081T &gt; A (p. Tyr361Asn) and a whole deletion (Ex1-19 del), were found in the MIPEP gene, which were inherited from his healthy parents respectively. Additionally, his mitochondria DNA copy number was significantly reduced.ConclusionWe are the first to report a patient with rare MIPEP variants in China. Our findings expand the mutation spectrum of MIPEP, and provide insights into the genotype-phenotype relationship in COXPD31

Ocular fundus pathology and chronic kidney disease in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Previous study indicated a high prevalence of ocular fundus pathology among patients with chronic kidney disease (CKD), while the relationship between them has never been explored in a Chinese Population.</p> <p>Methods</p> <p>This cross-sectional study included 9 670 participants enrolled in a medical screening program. Ocular fundus examination was performed by ophthalmologists using ophthalmoscopes. The presence of eGFR less than 60 mL/min/1.73 m²and/or proteinuria was defined as CKD.</p> <p>Results</p> <p>Compared to participants without CKD, participants with CKD had higher prevalence of retinopathy (28.5% vs. 16.3%, P < 0.001), glaucoma suspect (3.1% vs. 1.8%, P = 0.004), age-related macular degeneration (1.7% vs. 0.9%, P = 0.01) and overall eye pathology (32.0% vs. 19.4%, P < 0.001). After adjusting for potential confounders, the odds ratio of proteinuria for overall eye pathology and retinopathy was 1.29 (95% confidence interval [CI] 1.07-1.55) and 1.37 (95% CI 1.12-1.67), respectively. The results were robust after excluding participants with hypertension or with diabetes.</p> <p>Conclusions</p> <p>Ocular fundus pathology is common among Chinese patients with CKD. Regular eye exam among persons with proteinuria is warranted.</p

Management of Abnormal Visual Developments

When human beings recognize the external world, more than 80% of the information come from visual function and visual system. Normal visual development and normal binocularity are the fundamental of good visual acuity and visual functions. Any abnormal visual experience would cause abnormality, such as refractive error, strabismus, amblyopia and other diseases. The patients with abnormal visual developments were reported to have abnormal, lonely, and other psycho problems. In this chapter, we will describe the normal developmental of visual function, summarize the abnormal developments and the correction or treatment