Polygala fallax Hemsl. ameliorated high glucose-induced podocyte injury by modulating mitochondrial mPTP opening through the SIRT1/PGC-1α pathway.

This study aimed to investigate the effects and molecular mechanism of PF on high glucose (HG)-induced podocyte injury. Results found that PF increased proliferation activity, decreased apoptosis, LDH, and caspase-3 levels, and increased nephrin and podocin expression in HG-induced cells. Similarly, PF improved HG-induced mitochondrial damage, decreased Ca2+ and ROS content, alleviated oxidative stress, inhibited mPTP opening, increased mitochondrial membrane potential, and decreased the expressions of Drp1, Bak, Bax, and Cytc in cytoplasm, increased the expressions of SIRT1, PGC-1α, HSP70, HK2, and Cytc in mitochondria of podocytes. The use of mPTP agonist/blocker and SIRT1 inhibitor confirmed that PF alleviates HG-induced podocyte injury by regulating mitochondrial mPTP opening through SIRT1/PGC-1α. In addition, PF affected HK2-VDAC1 protein binding to regulate mPTP opening via the SIRT1/PGC-1α pathway. In conclusion, PF-regulated HK2-VDAC1 protein binding affected mitochondrial mPTP opening and improved HG-induced podocyte injury through the SIRT1/PGC-1α pathway.

Reduced Retinal Vascular Density and Skeleton Length in Amblyopia.

Purpose: This study aimed to investigate the possible relationship between retinal vascular abnormalities and amblyopia by analyzing vascular structures of fundus images. Methods: In this observational study, retinal fundus images were collected from 36 patients with unilateral amblyopia, 33 patients with bilateral amblyopia, and 36 healthy control volunteers. We developed a customized training algorithm based on U-Net to digitalize the vasculature in the fundus images to quantify vascular density (area and fractal dimension), skeleton length, and number of bifurcation points. For statistical comparisons, this study divided participants into two groups. The amblyopic eyes and the fellow eyes of patients with unilateral amblyopia formed the paired group, while bilateral amblyopic patients and healthy controls formed the independent group. Results: In the paired group, the vascular area (P = 0.007), vascular fractal dimension (P = 0.007), and vascular skeleton length (P = 0.002) of the amblyopic eyes were significantly smaller than those of the fellow eyes. In the independent group, significant decreases in the vascular fractal dimension (P = 0.006) and skeleton length (P = 0.048) were observed in bilateral amblyopia compared to control. The vascular area was also significantly correlated with best-corrected visual acuity in amblyopic eyes. Conclusions: This study demonstrated that retinal vascular density and skeleton length in amblyopic eyes were significantly smaller compared to control, indicating an association between the changes in retinal vascular features and the state of amblyopia. Translational Relevance: Our algorithm presents amblyopic retinal vascular changes that are more biologically interpretable for both clinicians and researchers.

Lycopene in hydrophobic deep eutectic solvent with natural catalysts: A promising strategy to simultaneously promote lycopene Z-isomerization and extraction.

Lycopene Z-isomerization and degradation in a series of hydrophobic natural deep eutectic solvents (HNDES) was firstly studied. The highest lycopene retention (about 84.6%) was found in HNDES composed of thymol and menthol (TM), and fatty acid-based HNDES promoted lycopene Z-isomerization (about 70% for total Z-isomers) and degradation. The addition of allyl isothiocyanate (AITC), diallyl disulfide (DADS) and capric acid into TM promoted Z-isomerization of lycopene (80% for total Z-isomers), especially 5Z-isomer (>30%), while lycopene remaining rate in TM/-capric acid was below 20%. During lycopene extraction from tomato power and watermelon juice by TM, the ratios of Z-isomer significantly (p < 0.05) increased especially with AITC and DADS (up to about 80%), and extraction yields increased even > 100% with capric acid. Lycopene in TM/-capric acid extracts showed low degradation with Z-isomers increasing during storage. TM with capric acid could simultaneously promote lycopene Z-isomerization and extraction.

The efficacy and safety of antibiotics and glucocorticoids in the treatment of elderly patients with chronic obstructive emphysema: systematic review and meta-analysis.

Background: To systematically evaluate the efficacy and safety of inhaled corticosteroids (ICS) combined with antibiotics in the treatment of elderly chronic obstructive pulmonary disease (COPD) patients, and to provide some reference for the optimization of clinical treatment regimen for elderly COPD patients. Methods: Combination of perfect search and keywords from the Chinese and foreign language databases, and the Cochrane Collaboration Center provided Review Manger 5.2 software [Cochrane Information Management System (IMS)] for statistical analysis, and the risk ratio (RR) of dichotic variables was adopted. RR and 95% confidence interval (95% CI) were used as efficacy and side effects analysis statistics in metaanalysis. Results: After independent screening by two researchers, 18 studies were included into the meta-analysis. After data analysis and statistics, the results of meta-analysis showed that the observation group (glucocorticoid combined with antibiotic treatment) and the control group (glucocorticoid therapy) first second forced expiratory volume (FEV1%) expected value (OR =1.21; 95% CI: 0.11-2.32; P=0.03), and 6-min walking distances (6-MWDs) (OR =12.92; 95% CI: 4.61-21.22; P=0.002), the COPD Assessment Test (CAT) score (OR =3.08; 95% CI: 2.58-3.57; P<0.00001) the improvement was statistically significant; incidence of adverse reactions (OR =1.24; 95% CI: 0.58-2.67; P=0.58), the incidence of acute exacerbation (OR =0.65; 95% CI: 0.39-1.08; P=0.10), FEV1 (OR =0.07; 95% CI: 0.01-0.15; P=0.09). There was no statistical difference. Discussion: The combination of glucocorticoids and antibiotics in elderly patients with stable COPD can significantly improve their lung function and exercise ability with minimal adverse reactions.

A Cytoplasm-Enriched circRNA circ-MYBL2 is Downregulated in Non-Small Cell Lung Cancer and Sponges Oncogenic miR-28 to Regulate Cancer Cell Proliferation and Apoptosis.

BACKGROUND: Recent studies have reported different roles of circRNA circ-MYBL2 in different cancers. However, the involvement of circ-MYBL2 in non-small cell lung cancer (NSCLC) is unknown. This study was carried out to explore the role of circ-MYBL2 in NSCLC. METHODS: The expression of circ-MYBL2 and miR-28 was detected by RT-qPCR. A 5-year follow-up study was performed for survival analysis. Nuclear fractionation assay was used for subcellular localization analysis. RNA pull-down assay was performed to detect the interaction between circ-MYBL2 and miR-28. The role of circ-MYBL2 and miR-28 in regulating the expression of each other was evaluated by overexpression assay. BrdU incorporation assay and cell apoptosis assay were performed to investigate the role of circ-MYBL2 and miR-28 in cell proliferation and apoptosis. RESULTS: NSCLC tissues exhibited significantly higher expression levels of miR-28 and lower expression levels of circ-MYBL2. Close correlations between circ-MYBL2 and miR-28 and patients' survival were observed. Circ-MYBL2, which was found to be mainly enriched in cytoplasm, directly interacted with miR-28. Although circ-MYBL2 and miR-28 showed no regulatory role in the expression of each other, circ-MYBL2 suppressed the effects of miR-28 on cell proliferation and apoptosis. CONCLUSION: Circ-MYBL2 is enriched in cytoplasm, and it sponges oncogenic miR-28 to suppress cancer cell proliferation in NSCLC and promote cell apoptosis.

Modulation of Guard Cell Turgor and Drought Tolerance by a Peroxisomal Acetate-Malate Shunt.

In plants, stomatal movements are tightly controlled by changes in cellular turgor pressure. Carbohydrates produced by glycolysis and the tricarboxylic acid cycle play an important role in regulating turgor pressure. Here, we describe an Arabidopsis mutant, bzu1, isolated in a screen for elevated leaf temperature in response to drought stress, which displays smaller stomatal pores and higher drought resistance than wild-type plants. BZU1 encodes a known acetyl-coenzyme A synthetase, ACN1, which acts in the first step of a metabolic pathway converting acetate to malate in peroxisomes. We showed that BZU1/ACN1-mediated acetate-to-malate conversion provides a shunt that plays an important role in osmoregulation of stomatal turgor. We found that the smaller stomatal pores in the bzu1 mutant are a consequence of reduced accumulation of malate, which acts as an osmoticum and/or a signaling molecule in the control of turgor pressure within guard cells, and these results provided new genetic evidence for malate-regulated stomatal movement. Collectively, our results indicate that a peroxisomal BZU1/ACN1-mediated acetate-malate shunt regulates drought resistance by controlling the turgor pressure of guard cells in Arabidopsis.

Induced metal redistribution and bioavailability enhancement in contaminated river sediment during in situ biogeochemical remediation.

In situ sediment remediation using Ca(NO3)2 or CaO2 for odor mitigation and acid volatile sulfide (AVS) and organic pollutant (such as TPH and PAHs) removal was reported in many studies and fieldwork. Yet, the associated effects on metal mobilization and potential distortion in bioavailability were not well documented. In this study, contaminated river sediment was treated by Ca(NO3)2 and CaO2 in bench studies. Through the investigation of AVS removal, organic matter removal, the changes in sediment oxidation-reduction potential (ORP), microbial activity, and other indigenous parameters, the effects on metal bioavailability, bioaccessibility, and fraction redistribution in sediment were evaluated. The major mechanisms for sediment treated by Ca(NO3)2 and CaO2 are biostimulation with indigenous denitrifying bacteria and chemical oxidation, respectively. After applying Ca(NO3)2 and CaO2, the decreases of metal concentrations in the treated sediment were insignificant within a 35-day incubation period. However, the [SEMtot-AVS]/f OC increased near to the effective boundary of toxicity (100 µmol g(-1) organic carbon (OC)), indicating that both bioavailability and bioaccessibility of metals (Cu, Zn, and Ni) to benthic organisms are enhanced after remediation. Metals were found redistributed from relatively stable fractions (oxidizable and residual fractions) to weakly bound fractions (exchangeable and reducible fractions), and the results are in line with the enhanced metal bioavailability. Compared with Ca(NO3)2, CaO2 led to higher enhancement in metal bioavailability and bioaccessibility, and more significant metal redistribution, probably due to its stronger chemical reactive capacity to AVS and sediment organic matter. The reactions in CaO2-treated sediment would probably shift from physicochemical to biochemical heterotrophic oxidation for sediment organic matter degradation. Therefore, further investigation on the long-term metal redistribution and associated mobility as well as bioavailability is recommended.

[Relationship between serum homocysteine level and oxidative stress in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the relationship between serum homocysteine (Hcy) level and oxidative stress in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Patients undergoing overnight full polysomnography (PSG) were selected from Sleep Disorders Center at First Affiliated Hospital between June 2008 and December 2013. A total of 117 OSAHS patients were recruited and divided into 3 groups of mild (n = 41), moderate (n = 40) and severe (n = 36). And they were compared with the controls (n = 33). The PSG variables were recorded and the contents of Hcy, malonaldehyde (MDA) and glutathione (GSH) detected after sleep. Serum Hcy was measured by cyclophorase. And MDA and GSH were measured by spectrophotometer. RESULTS: The concentrations of MDA in severe group were higher than those in the other three groups ((7.3 ± 1.0) vs (4.6 ± 0.9), (5.4 ± 1.3), (6.8 ± 0.7) µmol/L, all P < 0.05). The concentrations of GSH in mild and moderate groups were both higher than the controls ((6.5 ± 2.1), (7.5 ± 1.5) vs (4.2 ± 1.4) mg/L, all P < 0.05). However there was no significant difference between severe group ((4.6 ± 1.4) mg/L) and controls (P > 0.05). The Hcy level in mild and moderate groups were both higher than the controls ((10.3 ± 2.0), (13.3 ± 2.6) vs (8.7 ± 0.7) µmol/L, all P < 0.05). However there was no significant difference between severe group ((9.5 ± 1.8) µmol/L) and controls (P > 0.05). When severe group was removed, multielement linearity regression analysis indicated that there was a statistically significant relationship between Hcy concentration and age, MDA, GSH, apnea hypopnea index (AHI) and oxygen desaturation index (ODI) (P = 0.011, 0.005, 0.008, 0.001, 0.016 respectively). CONCLUSIONS: The change of marker levels in oxidative stress is not entirely consistent with the antioxidant levels in OSAHS patients at different stages of disease. The change of Hcy level is proportional to GSH level, but not proportional to severity in OSAHS patients. The mechanism of serum Hcy change may be oxidative stress in OSAHS patients.

Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice.

BACKGROUND: Immunosuppressive regulatory T cells (Tregs) participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 (FoxP3) in the aging process and its relationship with lung tumors in humans and mice. METHODS: The percentage of CD4(+)CD25(+)CD127(low) Tregs and expression of FoxP3 mRNA were analyzed using flow cytometry (FCM) and real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). Markers were analyzed in the peripheral blood (PB) of 65 elderly patients (age ≥ 65 years) with primary non-small cell lung cancer (NSCLC), 20 younger patients (aged < 55 years) with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, an elderly healthy group, a young tumor group, a middle-aged tumor group, and an elderly tumor group. The percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups. RESULTS: The percentage of peripheral CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis (TNM) staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice. CONCLUSIONS: The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.

An association between immunosenescence and CD4(+)CD25(+) regulatory T cells: a systematic review.

OBJECTIVE: Age-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. METHODS: Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. RESULTS: It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8(+) T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4(+)CD25(+) T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4(+) T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. CONCLUSIONS: Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.