Symptom networks analysis among people with Meniere's disease: Application for nursing care.

Objectives: This study aimed to explore and visualize the relationships among multiple symptoms in patients with Meniere's disease (MD) and aid clinical nurses in the design of accurate, individualized interventions. Methods: This study included 790 patients with MD at the Eye and ENT Hospital of Fudan University from October 2014 to December 2021. A self-designed symptom checklist was used to assess 15 MD-related symptoms and construct contemporaneous networks with all 15 symptoms in R software. Qgraph package and Fruchterman-Reingold layout were used for network visualization. Bootstrapping methods were performed to assess network accuracy and stability, and three centrality indices were adopted to describe relationships among symptoms. Results: Symptom networks showed good accuracy and stability. "Anxiety and nervousness"(98.2%), "aural fullness"(84.4%) and "tinnitus"(82.7%) were the common symptom in MD patients, while "tinnitus", "aural fullness" and "decline in word recognition", were more serious. MD patients with longer disease duration had higher prevalence and severity for all symptoms (P < 0.05). Symptom networks showed good accuracy and stability. "Decline in word recognition," "fatigue," and "anxiety and nervousness" were at the center of the symptom networks, which had the largest strength values and closeness. "Decline in word recognition," "headache," and "spatial discrimination and poor orientation" were the symptoms with the highest betweenness with the strongest bridging effect. The ≥1-year disease group exhibited higher centralities for "drop attack" and "anxiety and nervousness," and a lower centrality for "headache" compared with the <1-year disease group. Conclusions: The symptom networks of MD patients with varying disease durations were revealed. Clinicians and nurses must provide precision interventions tailored to modifying symptom severity and centrality. Nursing interventions should focus on word recognition issues and associated discomfort in MD patients with multiple symptoms.

Chinese cherry CpMYB44-CpSPDS2 module regulates spermidine content and florescence in tobacco.

The flower bud differentiation plays a crucial role in cherry yield and quality. In a preliminary study, we revealed the promotion of spermidine (Spd) in bud differentiation and quality. However, the molecular mechanism underlying Spd regulating cherry bud differentiation remains unclear. To address this research gap, we cloned CpSPDS2, a gene that encodes Spd synthase and is highly expressed in whole flowers and pistils of the Chinese cherry (cv. 'Manaohong'). Furthermore, an overexpression vector with this gene was constructed to transform tobacco plants. The findings demonstrated that transgenic lines exhibited higher Spd content, an earlier flowering time by 6 d, and more lateral buds and flowers than wild-type lines. Additionally, yeast one-hybrid assays and two-luciferase experiments confirmed that the R2R3-MYB transcription factor (CpMYB44) directly binds to and activates the CpSPDS2 promoter transcription. It is indicated that CpMYB44 promotes Spd accumulation via regulating CpSPDS2 expression, thus accelerating the flower growth. This research provides a basis for resolving the molecular mechanism of CpSPDS2 involved in cherry bud differentiation.

Overexpression of PavbHLH28 from Prunus avium enhances tolerance to cold stress in transgenic Arabidopsis.

BACKGROUND: The basic helix-loop-helix (bHLH) gene family is one of plants' largest transcription factor families. It plays an important role in regulating plant growth and abiotic stress response. RESULTS: In this study, we determined that the PavbHLH28 gene participated in cold resistance. The PavbHLH28 gene was located in the nucleus and could be induced by low temperature. Under the treatment of ABA, PEG, and GA3, the transcript level of PavbHLH28 was affected. At low temperature, overexpression of the PavbHLH28 gene enhanced the cold resistance of plants with higher proline content, lower electrolyte leakage (EL) and malondialdehyde (MDA) content. Compared with the WT plants, the transgenic plants accumulated fewer reactive oxygen species (ROS), and the activity and expression levels of antioxidant enzymes were significantly increased. The expression of proline synthesis enzyme genes was up-regulated, and the transcripts levels of degradation genes were significantly down-regulated. The transcripts abundance of the cold stressed-related genes in the C-repeat binding factor (CBF) pathway was not significantly different between WT plants and transgenic plants after cold stress. Moreover, the PavbHLH28 could directly bind to the POD2 gene promoter and promote its gene expression. CONCLUSIONS: Overall, PavbHLH28 enhanced the cold resistance of transgenic plants through a CBF-independent pathway, which may be partly related to ROS scavenging.

METTL3-mediated m6A modification of SIRT1 mRNA inhibits progression of endometriosis by cellular senescence enhancing.

BACKGROUND: Endometriosis (EMs), the ectopic planting of functional endometrium outside of the uterus, is a leading cause of infertility and pelvic pain. As a fundamental mRNA modification, N6-methyladenosine (m6A) participates in various pathological processes. However, the role of m6A RNA modification in endometriosis remains unclear. The present study explores METTL3-mediated m6A modification and the mechanisms involved in endometriosis. METHODS: The dominant m6A regulators in EMs were analysed using RT‒PCR. Candidate targets and possible mechanisms of METTL3 were assessed by m6A-mRNA epitranscriptomic microarray and RNA sequencing. A primary ESCs model was employed to verify the effect of METTL3 on m6A modification of SIRT1 mRNA, and the mechanism was elucidated by RT‒PCR, Western blotting, MeRIP, and RIP assays. CCK-8 viability assays, Transwell invasion assays, EdU proliferation assays, wound healing migration assays, and senescence-associated ß-galactosidase staining were performed to illuminate the potential biological mechanism of METTL3 and SIRT1 in ESCs in vitro. An in vivo PgrCre/ + METTL3 -/- female homozygous mouse model and a nude mouse xenograft model were employed to further investigate the physiologic consequences of METTL3-mediated m6A alteration on EMs. RESULTS: Our data show that decreased METTL3 expression significantly downregulates m6A RNA methylation levels in ESCs. Silencing m6A modifications mediated by METTL3 accelerates ESCs viability, proliferation, migration, and invasion in vitro. The m6A reader protein YTHDF2 binds to m6A modifications to induce the degradation of SIRT1 mRNA. SIRT1/FOXO3a signalling pathway activation is subsequently inhibited, promoting the cellular senescence of ESCs and inhibiting the ectopic implantation of ESCs in vitro and in vivo. CONCLUSIONS: Our findings demonstrate that METTL3-mediated m6A methylation epigenetically regulates the ectopic implantation of ESCs, resulting in the progression of endometriosis. Our study establishes METTL3-YTHDF2-SIRT1/FOXO3a as a critical axis and potential mechanism in endometriosis.

Simultaneous real-time analysis of tear film optical quality dynamics and functional visual acuity in dry eye disease.

BACKGROUND: To assess the effect of tear film instability in dry eye disease (DED) by measuring visual performance and tear film optical quality in a simultaneous real-time analysis system. METHODS: Thirty-seven DED participants and 20 normal controls were recruited. A simultaneous real-time analysis system was developed by adding a functional visual acuity (FVA) channel to a double-pass system. Repeated measurements of FVA and objective scatter index (OSI) were performed simultaneously with this system under blink suppression condition for 20 s. Patient-reported symptoms was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Mean FVA, mean OSI, and visual acuity break-up time were defined. The OSI maintenance ratio was calculated as an evaluation index to assess the difference between dynamic OSI changes and baseline OSI. The visual maintenance ratio was also calculated in the same way. RESULTS: Moderate correlations were noted between mean OSI and FVA-related parameters (mean FVA, visual maintenance ratio, visual acuity break-up time: 0.53, - 0.56, - 0.53, respectively, P < 0.01 for all). Moderate to high correlations were noted between OSI maintenance ratio and FVA-related parameters (mean FVA, visual maintenance ratio, visual acuity break-up time: - 0.62, 0.71, 0.64, respectively, all P < 0.01). The metrics derived from the simultaneous real-time analysis system were moderately correlated with the patient-reported symptoms and the visual acuity break-up time possessed the highest correlation coefficients with OSDI total, ocular symptoms, and vision-related function (- 0.64, - 0.63, - 0.62, respectively, P < 0.01). The OSI-maintenance ratio alone appeared to exhibit the best performance of the metrics for the detection of DED with sensitivity of 95.0% and specificity of 83.8% and the combinations of FVA parameters and OSI parameters were valid and can further improve the discriminating abilities. CONCLUSIONS: OSI-related metrics were found to be potential indicators for assessing and diagnosing DED which correlated with both subjective visual performance and patient-reported symptoms; the FVA-related metrics were quantifiable indicators for evaluating visual acuity decline in DED. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100051650. Registered 29 September 2021, https://www.chictr.org.cn/showproj.aspx?proj=134612.

Cross-Talk between Transcriptome Analysis and Dynamic Changes of Carbohydrates Identifies Stage-Specific Genes during the Flower Bud Differentiation Process of Chinese Cherry (Prunus pseudocerasus L.).

Flower bud differentiation is crucial to reproductive success in plants. In the present study, RNA-Seq and nutrients quantification were used to identify the stage-specific genes for flower bud differentiation with buds which characterize the marked change during flower bud formation from a widely grown Chinese cherry (Prunus pseudocerasus L.) cultivar 'Manaohong'. A KEGG enrichment analysis revealed that the sugar metabolism pathways dynamically changed. The gradually decreasing trend in the contents of total sugar, soluble sugar and protein implies that the differentiation was an energy-consuming process. Changes in the contents of D-glucose and sorbitol were conformed with the gene expression trends of bglX and SORD, respectively, which at least partially reflects a key role of the two substances in the transition from physiological to morphological differentiation. Further, the WRKY and SBP families were also significantly differentially expressed during the vegetative-to-reproductive transition. In addition, floral meristem identity genes, e.g., AP1, AP3, PI, AGL6, SEP1, LFY, and UFO demonstrate involvement in the specification of the petal and stamen primordia, and FPF1 might promote the onset of morphological differentiation. Conclusively, the available evidence justifies the involvement of sugar metabolism in the flower bud differentiation of Chinese cherry, and the uncovered candidate genes are beneficial to further elucidate flower bud differentiation in cherries.

Copper Amine Oxidase (CuAO)-Mediated Polyamine Catabolism Plays Potential Roles in Sweet Cherry (Prunus avium L.) Fruit Development and Ripening.

Copper amine oxidases (CuAOs) play important roles in PA catabolism, plant growth and development, and abiotic stress response. In order to better understand how PA affects cherry fruit, four potential PavCuAO genes (PavCuAO1-PavCuAO4) that are dispersed over two chromosomes were identified in the sweet cherry genome. Based on phylogenetic analysis, they were classified into three subclasses. RNA-seq analysis showed that the PavCuAO genes were tissue-specific and mostly highly expressed in flowers and young leaves. Many cis-elements associated with phytohormones and stress responses were predicted in the 2 kb upstream region of the promoter. The PavCuAOs transcript levels were increased in response to abscisic acid (ABA) and gibberellin 3 (GA3) treatments, as well as abiotic stresses (NaCl, PEG, and cold). Quantitative fluorescence analysis and high-performance liquid chromatography confirmed that the Put content fell, and the PavCuAO4 mRNA level rose as the sweet cherry fruit ripened. After genetically transforming Arabidopsis with PavCuAO4, the Put content in transgenic plants decreased significantly, and the expression of the ABA synthesis gene NCED was also significantly increased. At the same time, excessive H2O2 was produced in PavCuAO4 transiently expressed tobacco leaves. The above results strongly proved that PavCuAO4 can decompose Put and may promote fruit ripening by increasing the content of ABA and H2O2 while suppressing total free PA levels in the fruit.

Research on the oxidation characteristics of zinc sulfite in the zinc oxide desulfurization process.

Aiming at the pollution problem of low-content SO2 in non-ferrous metal production industry, the oxidation kinetics of zinc sulfite in the zinc oxide desulfurization process was studied. The concentration change of Zn2+, variation of pH, temperature and apparent activation energy in the oxidation process of two ZnSO3 samples were investigated systematically. The results indicate that the raw material with different crystal water has little effect on the oxidation kinetic of zinc sulfite. The reaction process comprises two stages: the dissolution process and the oxidation process. The zinc ion concentration is linearly rising with the action time during the oxidation process. The pH value rises quickly in the dissolution process and goes down slowly with reaction time in the oxidation process. The process is mainly controlled by a diffusion step and less effected by the temperature. The apparent activation energy Ea obtained for the two samples are 8.662 and 9.645 kJ/mol, respectively. Integrated with the kinetic model, the oxidation rate of zinc sulfite is controlled by the diffusion of HSO3- and O2 to the gas-liquid interface.

Newly generated and increased bound phenolic in lychee pulp during heat-pump drying detected by UPLC-ESI-triple-TOF-MS/MS.

BACKGROUND: During the thermal processing of fruit, it has been observed for phenolic compounds to either degrade, polymerize, or transfer into macromolecules. In this study, the bound and free phenolic compound composition, content, and phenolic-related enzyme activity of lychee pulp were investigated to determine whether the free phenolic had converted to bound phenolic during heat-pump drying (HPD). RESULTS: It was found that after HPD, when compared with the fresh lychee pulp (control), the content of bound phenolics of dried lychee pulp had increased by 62.69%, whereas the content of free phenolics of dried lychee pulp decreased by 22.26%. It was also found that the antioxidant activity of bound phenolics had also increased after drying. With the use of high-performance liquid chromatography-tandem mass spectrometry, it was identified that (+)-gallocatechin, protocatechuic aldehyde, isorhamnetin-3-O-rutoside, 3,4-dihydroxybenzeneacetic acid, and 4-hydroxybenzoic acid were newly generated during HPD, when compared with the control sample. After drying, the contents of gallic acid, catechin, 4-hydroxybenzoic acid, vanillin, syringic acid, and quercetin in bound phenolics had also increased, and polyphenol oxidase and peroxidase still showed enzyme activity, which could be related to the conversion of free phenolics to bound phenolics. CONCLUSION: Overall, during the thermal processing of lychee pulp, the free phenolics weres found to be converted into bound phenolics, new substances were generated, and antioxidant activity was increased. Hence, it was concluded that HPD improved the bound phenolics content of lychee pulp, thus providing theoretical support for the lychee processing industry. © 2021 Society of Chemical Industry.

Vortex fluidics mediated non-covalent physical entanglement of tannic acid and gelatin for entrapment of nutrients.

We have developed a simple process for the entrapment of nutrients in shear stress induced non-covalent physically entangled tannic acid-gelatin gel in a thin film vortex fluidic device (VFD) operating under continuous flow. This allows control of the porosity and surface area of the pores in order to improve the nutrient entrapment capacity. The VFD microfluidic platform simplifies the processing procedure of physically entangled biopolymers, as a time and cost saving one-step process devoid of any organic solvents, in contrast to the conventional homogenization process, which is also inherently complex, involving multiple-step processing. Moreover, the use of homogenization (as a benchmark to entrap nutrients) afforded much larger porosity and surface area of pores, with lower entrapment capacity of nutrients. Overall, the VFD processing provides a new alternative, bottom-up approach for easy, scalable processing for materials with a high nutrient entrapment capacity.

In vitro simulated digestion and colonic fermentation of lychee pulp phenolics and their impact on metabolic pathways based on fecal metabolomics of mice.

Lychee pulp phenolics (LPP) was subjected to four simulated gastrointestinal digestions and colonic fermentation to investigate the changes in its phenolic composition and bioactivities; the fecal metabolic profiles of LPP-fed mice were also elucidated using UHPLC-ESI-QTOF-MS/MS. After simulated salivary, gastric and intestinal digestion, slight increases in phenolic acids and (+)-catechin occurred relative to undigested LPP, whereas other flavonoids showed an opposite trend. Unlike the above-described separate simulated digestions, successive gastrointestinal digestion significantly enhanced the release of phenolic compounds (p < 0.05), gallic acid (413.79%), ferulic acid (393.69%), (+)-catechin (570.27%) and rutin (247.54%). During colonic fermentation, ten detected phenolics were utilized by gut microbes, among which procyanidin B2 (22.35%) was the most degraded. LPP fermentation accelerated the production of short-chain fatty acids (122.79%). The metabolic pathways altered by LPP including unsaturated fatty acid, biotin, and nicotinamide metabolism may be the potential regulatory mechanisms and associated with the integrity of the gut barrier. These findings indicate that LPP may act as a promising candidate to protect gut health.

Intestinal Population in Host with Metabolic Syndrome during Administration of Chitosan and Its Derivatives.

Chitosan and its derivatives can alleviate metabolic syndrome by different regulation mechanisms, phosphorylation of AMPK (AMP-activated kinase) and Akt (also known as protein kinase B), suppression of PPAR-γ (peroxisome proliferator-activated receptor-γ) and SREBP-1c (sterol regulatory element-binding proteins), and translocation of GLUT4 (glucose transporter-4), and also the downregulation of fatty-acid-transport proteins, fatty-acid-binding proteins, fatty acid synthetase (FAS), acetyl-CoA carboxylase (acetyl coenzyme A carboxylase), and HMG-CoA reductase (hydroxy methylglutaryl coenzyme A reductase). The improved microbial profiles in the gastrointestinal tract were positively correlated with the improved glucose and lipid profiles in hosts with metabolic syndrome. Hence, this review will summarize the current literature illustrating positive correlations between the alleviated conditions in metabolic syndrome hosts and the normalized gut microbiota in hosts with metabolic syndrome after treatment with chitosan and its derivatives, implying that the possibility of chitosan and its derivatives to serve as therapeutic application will be consolidated. Chitosan has been shown to modulate cardiometabolic symptoms (e.g., lipid and glycemic levels, blood pressure) as well as gut microbiota. However, the literature that summarizes the relationship between such metabolic modulation of chitosan and prebiotic-like effects is limited. This review will discuss the connection among their structures, biological properties, and prebiotic effects for the treatment of metabolic syndrome. Our hope is that future researchers will consider the prebiotic effects as significant contributors to the mitigation of metabolic syndrome.

A Positive Feedback Loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-1α Plays a Role in the Progression of Ovarian Cancer.

BACKGROUND: Accumulating studies have revealed that long non-coding RNA (lncRNA) and microRNA (miRNA) contribute to ovarian cancer (OC). DSCR8 has been found to mediate hepatocellular carcinoma development, while its role in OC remains to be explored. METHODS: In this study, lncRNA DSCR8 and miR-98-5p expressions in OC tissues and adjacent non-cancer tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Besides, gain-of-function or loss-of-function assays of DSCR8 and miR-98-5p were conducted on OC cell lines SKOV-3 and A2780. Cell proliferation was detected with Cell Counting Kit (CCK)8 and colony formation assay, and western blot was used to test the apoptotic levels of OC cells. Transwell assay was conducted to examine cell invasion, and the epithelial-mesenchymal transition (EMT) of OC cells was tested by western blot. Moreover, luciferase activity assay and RNA immunoprecipitation (RIP) assay were conducted to verify the relationships between DSCR8 and miR-98-5p, miR-98-5p, and signal transducer and activator of transcription 3 (STAT3). RESULTS: DSCR8 was remarkedly increased in OC tissues and associated with poorer survival of OC patients. Overexpressing DSCR8 promoted cell proliferation, invasion, and EMT but inhibited apoptosis. On the other hand, miR-98-5p was downregulated in OC tissues and relieved the progression of OC. Moreover, overexpressed DSCR8 increased the levels of STAT3 and hypoxia inducible factor 1 alpha (HIF-1α) and dampened the functions of miR-98-5p on OC. Pharmaceutical intervention of STAT3 and HIF-1α significantly altered the expressions of DSCR8 and miR-98-5p. CONCLUSION: The present results suggested a positive feedback loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-α axis in the progression of OC.

Effects of simulated digestion on the phenolic composition and antioxidant activity of different cultivars of lychee pericarp.

BACKGROUND: Lychee pericarp is rich in phenolic and has good antioxidant activity. The effects of simulated gastric (SGF) and intestinal fluid (SIF) digestion on the contents, composition, and antioxidant activities of the phenolic substances in the pericarp of different lychee cultivars (cv Jizui, Lizhiwang, Guiwei, Yuhe, Nuomici and Guihong) were investigated. RESULTS: Compared with distilled water (DW) treatment, the total phenolic content (TPC) and total flavonoid content (TFC) in the pericarp of different lychee cultivars decreased after SGF digestion; especially, the TFC in "Lizhiwang" decreased by 41.5%. The TPC and TFC of lychee pericarp also decreased after SIF digestion. However, the TPC in "Jizui", "Guiwei" and "Yuhe" increased. The SGF and SIF also had different effects on the FRAP and ABTS antioxidant activities of different lychee cultivars. The SGF digestion decreased the ABTS antioxidant capacity of lychee pericarp but enhanced the FRAP value of some lychee cultivars. However, the SIF digestion decreased the FRAP antioxidant activity of different lychee cultivar pericarps but enhanced the ABTS antioxidant capacity of lychee. The HPLC results showed that lychee pericarp had relatively high contents of procyanidin B2 and procyanidin A2. After SIF digestion, caffeic acid and isoquercitrin could not be detected in any of the lychee varieties. However, quercetin-3-rutinose-7-rhamnoside and isoquercitrin were increased after SGF digestion. CONCLUSIONS: Lychee pericarp could be used as an inexpensive functional food ingredient.

Triptolide interferes with XRCC1/PARP1-mediated DNA repair and confers sensitization of triple-negative breast cancer cells to cisplatin.

Triptolide is a natural compound isolated from the Tripterygium wilfordii, which possesses anti-inflammatory and anti-tumor activities. Triptolide reportedly inhibits RNA polymerase II-mediated transcription and ATM activities to interfere with DNA repair. However, the roles of triptolide in DNA repair are still largely unknown. Triple negative breast cancer cells (TNBC) are insensitive to targeted anti-tumoral drugs, thus DNA damage chemotherapeutic drugs are the available treatments used in clinic, while the drug resistance of TNBC causes the challenge for successful cure. In this study, we investigated the efficiency of cisplatin in combination with triptolide in treatment of TNBC. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows triptolide suppresses the growth of two triple-negative breast cancer cells, BT549 and MDA-MB-231. Triptolide induces DNA breaks and arrests TNBC in the cell cycle S phase, and sensitizes TNBC to cisplatin. Western blot analysis shows triptolide down-regulated the levels of PARP1 and XRCC1, and slightly decreases the levels of RAD51. The results demonstrate triptolide interferes with single strand-break and base excision repair. The over-expressed PARP1/XRCC1 help the TNBC to resist triptolide. Based on these results, we conclude triptolide confers sensitization of TNBC to cisplatin via interference with XRCC1/PARP1-mediated base excision repair.

Berberine activates caspase-9/cytochrome c-mediated apoptosis to suppress triple-negative breast cancer cells in vitro and in vivo.

Berberine (BBR) is an isoquinoline alkaloid isolated from Cotridis rhizoma and exhibits multiple biological roles including anti-microbe, anti-inflammation and anti-tumor activities. In this study, two triple-negative breast cancer cell (TNBC) lines, MDA-MB-231 and BT549, were used to investigate the effect of BBR on growth of TNBC in vitro and in vivo. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the viability of cells treated with BBR. After 48h treatments, a 50% inhibitory concentration (IC50) of BBR to BT549 and MDA-MB-231 cells are at 16.575±1.219µg/ml and 18.525±6.139µg/ml respectively. BBR reduced colony formation of BT549 and MDA-MB-231 cells. The wound-healing assay showed BBR decreased breast cancer cell migrations (P<0.01). AnnexinV-PI staining assay confirmed BBR induced cellular apoptosis. The expressions of caspase-3, caspase-9, Bcl-2 and Bax were detected by western blot, which showed BBR activated caspase-3, 9 and Bax, but down-regulated Bcl-2 expression. BBR promoted the release of cytochrome c through the immunofluorescent analysis (P<0.01). We also found BBR increased the level of cellular γH2AX and increased the expression of Ligase4, which suggests BBR induces the double-strand breaks (DSB). These results thus demonstrated that BBR induced DSB, subsequently increased the release of cytochrome c and eventually triggered the caspase9-dependent apoptosis. In addition, we used a MDA-MB-231 mouse-xenograftmodel to evaluate the effect of BBR on tumor growth. BBR suppressed tumor growth and increased caspase-9 levels in xenograft tumors through immunohistochemistry analysis (P<0.01). Taken together, these results demonstrate that BBR activates caspase-9/cytochrome c-mediated apoptosis to inhibit the growth of TNBC breast cancer cells in vitro and in vivo.

Effects of Maydis stigma polysaccharide on the intestinal microflora in type-2 diabetes.

CONTEXT: Diabetes is a serious endocrine and metabolic disorder. Food supplements attract people's attention in mitigating health problems from the aspect of gastrointestinal microflora. Maydis stigma (Zea mays subsp. mays L. [Poaceae]), has been used as water decoction for treating diabetes in folk medicine. It has great potential, and feasibly a stable form of Maydis stigma commercial products could be developed to fulfil the health food market. OBJECTIVE: To study the effects of Maydis stigma polysaccharide (MSP) on the intestinal microflora in type-2 diabetes (T2D). MATERIALS AND METHODS: MSP was fractioned from Maydis stigma by distilled water, purified by DEAE-52 Cellulose chromatography and Sephadex G-200 gel column. Streptozotocin (160 mg/kg) was intraperitoneal injected for 3 days to build model. The diabetic mice were randomly divided into five groups together with control group (10 mice in each group). The doses of MSP were 400, 600 and 800 mg/kg, respectively. After 5 weeks of administration, antidiabetic effects and intestinal microflora balance restoring activities were evaluated by denaturing gradient gel electrophoresis. RESULTS: Blood glucose levels of MSP-treated groups showed extremely significant hypoglycemic effects (p < 0.01), body weight increased showed extremely significant (p < 0.01) differences. Bacteroides, Lactobacillus and Prevotella were dominant organisms in the intestinal tract. The quality and quantity of Lactobacillus and Bacteroides genus increased remarkably with increasing concentration of MSP. DISCUSSION AND CONCLUSION: Experimental results of this study suggest that MSP has the significant potential to be used as a natural agent for treating T2D and restoring the intestinal microflora balance.

P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3.

Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease.

Suppression of experimental autoimmune glomerulonephritis by tryptophan.

BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO), a heme-containing dioxygenase, can catalyze tryptophan degradation and produce a local microenvironment with tryptophan depletion and tryptophan metabolites accumulation, which may suppress T cell-mediated immunity and play an important immunosuppressive role in many diseases. Previous studies suggested that tryptophan depletion is an important immunosuppressive mechanism of IDO, while recent evidence shows that tryptophan metabolites may also be useful for inducing the T cell immune tolerance. However, it remains unclear whether tryptophan catabolites play a protective role in anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN), which is a type 1 T-helper (Th1)-mediated autoimmune disease. METHODS: We examined the effect of tryptophan catabolites, 3-hydroxykynurenine acid and 3-hydroxyanthranilic acid, on renal injury in experimental autoimmune glomerulonephritis (EAG) of Wistar-Kyoto rats and explored their protective mechanism. RESULTS: Treatment by either 3-hydroxyanthranilic acid or 3-hydroxykynurenic acid attenuated the kidney disease of EAG rats, with decreased glomerular histological injury and inflammatory cell infiltration, lightened urinary protein, and improved renal function compared to phosphate buffered saline-treated EAG rats. This was associated with significantly increased apoptosis and decreased proliferation of splenic activated T cells in vivo, inducing the deviation of cytokines of antigen-special T cells from Th1 to Th2. CONCLUSIONS: Tryptophan metabolites play an important immunosuppressive role in the development of anti-GBM GN and might offer a new strategy for treating this disease.

In vitro effects on intestinal bacterium of physalins from Physalis alkekengi var. Francheti.

Intestinal probiotic bacterium stimulative activity-guided fractionation of Physalis alkekengi var. Francheti calyces extract resulted in the isolation of four new physalins (1-4). Their structures were elucidated as 5α, 6ß-dihydroxy-25, 27-dihydro-7-deoxyphysalin A (1), 5α, 6ß-dihydroxyphysalin R (2), 3ß-hydroxy-2-hydrophysalin A (3) and 5α-hydroxy-7-dehydro-25, 27-dihydro-7-deoxyneophysalin A (4) by UV, MS, 1D and 2D NMR spectroscopy. Growth curves of Lactobacillus delbrueckii and Escherichia coli for different total physalins extract (TPE) concentrations were tested in vitro. Middle concentrations (0.78mg/mL-1.56mg/mL) of TPE promoted the growth of L. delbrueckii, but all inhibited the growth of E. coli, in which the bacteriostatic activity increased while TPE concentration increases. Physalins showed stimulative effects on the growth of probiotic bacteria but inhibitory effects on the growth of pathogenic bacteria.