Neutrophil profiling illuminates anti-tumor antigen-presenting potency.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.

Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the ß-catenin/LEF-1 pathway.

Background: In thyroid cancers, a reduction in the expression of the sodium/iodide symporter (NIS) is observed concomitant with a diminution in cancer cell differentiation. The ß-catenin/LEF-1 pathway emerges as a crucial regulatory pathway influencing the functional expression of NIS in human thyroid cancer cells. Further research is required to comprehensively elucidate the role of NIS overexpression in impeding the progression of thyroid cancer cells. Methods: Human papillary thyroid carcinoma (PTC) cell lines, specifically PTC-1 and KTC-1, were subjected to Scratch and Transwell assays, colony formation, and tumor sphere formation tests to investigate invasion and migration, focusing on the impact of NIS overexpression. The assessment involved the use of western blot to analyze the expression levels of ß-catenin, NIS, CD133, SRY-related HMG box2 (Sox2), lymphoid enhancer-binding factor 1 (LEF-1), NANOG, octamer-binding transcription factor 4 (Oct4), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and epithelial cellular adhesion molecule (EpCAM). Statistical analysis was conducted using SPSS version 20.0, and the graphs were developed using GraphPad Prism 7 (GraphPad Software, Inc.). Results: Our observations revealed that Nthy-ori-3-1 cell lines exhibited notably higher average expression levels of NIS, yet significantly lower levels of LEF-1 and ß-catenin compared to PTC-1 and KTC-1 cell lines. Furthermore, the overexpression of ß-catenin resulted in reduced binding of LEF-1 to NIF promotion but concurrently increased the expression of NIS. The downregulation of NIS markedly enhanced the expression of ALDH1A1, CD133, OCT4, Nanog, SOX2, and EpCam-all of which are targets within the Wnt/ß-catenin signaling pathway. Conversely, the upregulation of NIS suppressed the expression of these proteins. Moreover, cells treated with ß-catenin activators demonstrated an increased capability to form more spheroids and displayed heightened aggressiveness. Conversely, the NIS overexpression (OE) group exhibited suppressed abilities in invasion and colony formation. Conclusion: Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the ß-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer.

GLI family zinc finger protein 2 promotes skin fibroblast proliferation and DNA damage repair by targeting the miR-200/ataxia telangiectasia mutated axis in diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU.

Fabrication of 3D printed PCL/PEG artificial bile ducts as supportive scaffolds to promote regeneration of extrahepatic bile ducts in a canine biliary defect model.

In this study, a 3D porous poly(ε-caprolactone)/polyethylene glycol (PCL/PEG) composite artificial tubular bile duct was fabricated for extrahepatic bile duct regeneration. PCL/PEG composite scaffolds were fabricated by 3D printing, and the molecular structure, mechanical properties, thermal properties, morphology, and in vitro biocompatibility were characterized for further application as artificial bile ducts. A bile duct defect model was established in beagle dogs for in vivo implantation. The results demonstrated that the implanted PE1 ABD, serving as a supportive scaffold, effectively stimulated the regeneration of a new bile duct comprising CK19-positive and CK7-positive epithelial cells within 30 days. Remarkably, after 8 months, the newly formed bile duct exhibited an epithelial layer resembling the normal structure. Furthermore, the study revealed collagen deposition, biliary muscular formation, and the involvement of microvessels and fibroblasts in the regenerative process. In contrast, the anastomotic area without ABD implantation displayed only partial restoration of the epithelial layer, accompanied by fibroblast proliferation and subsequent bile duct fibrosis. These findings underscore the limited inherent repair capacity of the bile duct and underscore the beneficial role of the PE1 ABD artificial tubular bile duct in promoting biliary regeneration.

Exosomal circHIPK3 derived from umbilical cord-derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR-20b-5p/ULK1/Atg13 axis.

BACKGROUND: Umbilical cord-derived mesenchymal stem cells (UCMSCs) could alleviate diabetes-induced injury. Hence, this investigation aimed to explore the role and mechanism of UCMSCs-derived exosomal circHIPK3 (exo-circHIPK3) in diabetes mellitus (DM). METHODS: HFF-1 cells were cultured in high glucose (HG) medium or normal medium, and treated with UCMSCs-derived exo-circHIPK3 or miR-20b-5p mimics or Unc-51-like autophagy activating kinase 1 (ULK1) overexpression vector. The surface markers of UCMSCs were analyzed using a flow cytometer. The differentiation potential of UCMSCs was evaluated using oil red O staining, alizarin red staining and alkaline phosphatase (ALP) staining. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The miRNA expressions were analyzed by reverse transcription-quantitative polymerase chain reaction (qRT-PCR). Protein levels were quantified by western blot. An immunofluorescence staining was used for observing LC3 expression. The interaction between miR-20b-5p and circHIPK3, and between miR-20b-5b and ULK1 were identified by a RNA immunoprecipitation (RIP) assay and a luciferase reporter assay. RESULTS: Up-regulation of circHIPK3 was found in UCMSCs-derived exosomes. Exo-circHIPK3 decreased the miR-20b-5p level while increasing the contents of ULK1 and autophagy-related gene 13 (Atg13) in HG-induced fibroblasts. In addition, exo-circHIPK3 activated HG-induced fibroblast autophagy and proliferation. Overexpressed miR-20b-5p promoted fibroblast injury by inhibiting cell autophagy via the ULK1/Atg13 axis in HG conditions of high glucose. Moreover, exo-circHIPK3 enhanced autophagy and cell viability in HG-induced fibroblasts through the miR-20b-5p/ULK1/Atg13 axis. CONCLUSION: UCMSCs-derived exosomal circHIPK3 promoted cell autophagy and proliferation and accelerated the fibroblast injury repair by the miR-20b-5p/ULK1/Atg13 axis.

Delayed CO2 postconditioning promotes neurological recovery after cryogenic traumatic brain injury by downregulating IRF7 expression.

AIMS: Few treatments are available in the subacute phase of traumatic brain injury (TBI) except rehabilitation training. We previously reported that transient CO2 inhalation applied within minutes after reperfusion has neuroprotective effects against cerebral ischemia/reperfusion injury. In this study, it was hypothesized that delayed CO2 postconditioning (DCPC) starting at the subacute phase may promote neurological recovery of TBI. METHODS: Using a cryogenic TBI (cTBI) model, mice received DCPC daily by inhaling 5%/10%/20% CO2 for various time-courses (one/two/three cycles of 10-min inhalation/10-min break) at Days 3-7, 3-14 or 7-18 after cTBI. Beam walking and gait tests were used to assess the effect of DCPC. Lesion size, expression of GAP-43 and synaptophysin, amoeboid microglia number and glia scar area were detected. Transcriptome and recombinant interferon regulatory factor 7 (Irf7) adeno-associated virus were applied to investigate the molecular mechanisms. RESULTS: DCPC significantly promoted recovery of motor function in a concentration and time-course dependent manner with a wide therapeutic time window of at least 7 days after cTBI. The beneficial effects of DCPC were blocked by intracerebroventricular injection of NaHCO3 . DCPC also increased puncta density of GAP-43 and synaptophysin, and reduced amoeboid microglia number and glial scar formation in the cortex surrounding the lesion. Transcriptome analysis showed many inflammation-related genes and pathways were altered by DCPC, and Irf7 was a hub gene, while overexpression of IRF7 blocked the motor function improvement of DCPC. CONCLUSIONS: We first showed that DCPC promoted functional recovery and brain tissue repair, which opens a new therapeutic time window of postconditioning for TBI. Inhibition of IRF7 is a key molecular mechanism for the beneficial effects of DCPC, and IRF7 may be a potential therapeutic target for rehabilitation after TBI.

Effects of polystyrene nanoplastics on the physiological and biochemical characteristics of microalga Scenedesmusquadricauda.

The contamination of the aquatic environment with microplastics has become a global environmental concern. Microplastic particles can be shredded to form smaller nanoplastics, and knowledge on their impacts on phytoplankton, especially freshwater microalgae, is still limited. To investigate this issue, the microalga Scenedesmus quadricauda was exposed to polystyrene nanoplastics (PS-NPs) of five concentrations (10, 25, 50, 100, and 200 mg/L). The growth; the contents of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD); the chlorophyll content; and concentrations of soluble protein and soluble polysaccharide were accordingly measured. The results showed that the microalgal density increased with the increase of the polystyrene nanoplastic concentrations, and the physiological features of alga were enhanced after the stimulation of nanoplastics. Furthermore, a high concentration (200 mg/L) of nanoplastics increased the contents of chlorophyll, soluble protein, and polysaccharide (P < 0.05). The antioxidant enzyme activities of Scenedesmus quadricauda were significantly activated by nanoplastics. Lastly, we propose three possible algal recovery mechanisms in response to nanoplastics in which Scenedesmus quadricauda was tolerant with PS-NPs by cell wall thickening, internalization, and aggregation. The results of this study contribute to understanding of the ecological risks of nanoplastics on freshwater microalgae.

Systematic review of antitumour efficacy and mechanism of metformin activity in prostate cancer models.

Metformin, the first line pharmacotherapy for type 2 diabetes has demonstrated favourable effects in prostate cancer (PCa) across a range of studies evaluating PCa patient outcomes amongst metformin users. However, a lack of rigorously conducted prospective studies has stalled clinical use in this setting. Despite multiple studies evaluating the mechanisms underpinning antitumour effects of metformin in PCa, to date, no reviews have compared these findings. This systematic review and meta-analysis consolidates the mechanisms accounting for the antitumour effect of metformin in PCa and evaluates the antitumour efficacy of metformin in preclinical PCa studies. Data were obtained through Medline and EMBASE, extracted by two independent assessors. Risk of bias was assessed using the TOXR tool. Meta-analysis compared in vivo reductions of PCa tumour volume with metformin. In total, 447 articles were identified with 80 duplicates, and 261 articles excluded based on eligibility criteria. The remaining 106 articles were assessed and 71 excluded, with 35 articles included for systematic review, and eight included for meta-analysis. The mechanisms of action of metformin regarding tumour growth, viability, migration, invasion, cell metabolism, and activation of signalling cascades are individually discussed. The mechanisms by which metformin inhibits PCa cell growth are multimodal. Metformin regulates expression of multiple proteins/genes to inhibit cellular proliferation, cell cycle progression, and cellular invasion and migration. Published in vivo studies also conclusively demonstrate that metformin inhibits PCa growth. This highlights the potential of metformin to be repurposed as an anticancer agent, warranting further investigation of metformin in the setting of PCa.

UCMSCs-derived exosomal circHIPK3 promotes ulcer wound angiogenesis of diabetes mellitus via miR-20b-5p/Nrf2/VEGFA axis.

AIMS: Experiments confirmed that circular RNAs contributed to the pathogenesis of diabetic foot ulcers (DFUs). CircHIPK3 was upregulated in type 2 diabetes mellitus (T2DM), but its role in DFU remained unknown. Our study aimed to investigate the regulatory functions of exosomal circHIPK3 and its potential mechanisms in DFU. METHODS: Exosomal size and distribution, marker proteins, and circHIPK3 levels were evaluated by transmission electron microscope, ExoView R200, western blot, and qRT-PCR. Flow cytometry, MTT, Wound healing assays, and tube formation assays were used to assess the roles of exosomal circHIPK3 in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). The relationships between Nrf2/VEGFA/circHIPK3 and miR-20b-5p, and between Nrf2 and VEGFA were determined by luciferase reporter assay and RNA immunoprecipitation. We used cell and mice models to investigate the mechanisms of exosomal circHIPK3 under diabetic conditions. RESULTS: CircHIPK3 was significantly upregulated in exo-circHIPK3 rather than exo-vector. Exo-circHIPK3 remarkably inhibited cell apoptosis but promoted cell proliferation, migration, and tube formation in HG-treated HUVECs. Luciferase reporter and RIP assays showed that miR-20b-5p targeted and inhibited Nrf2 and VEGFA, and circHIPK3 acted as a ceRNA of miR-20b-5p to inhibit the binding to its downstream genes Nrf2 and VEGFA. Mechanistically, circHIPK3 promoted cell proliferation, migration, and angiogenesis via downregulating miR-20b-5p to upregulate Nrf2 and VEGFA. However, the overexpressed miR-20b-5p could abolish the promoting effects of circHIPK3 overexpression on cell proliferation, migration, and tube formation under HG conditions. CONCLUSION: UCMSCs-derived exosomal circHIPK3 protected HG-treated HUVECs via miR-20b-5p/Nrf2/VEGFA axis. The exosomal circHIPK3 might be a therapeutic candidate to treat DFU.

Radiation dose escalation for locally advanced nasopharyngeal carcinoma patients with local and/or regional residual lesions after standard chemoradiotherapy: a non-randomized, observational study.

BACKGROUND: To assess the effectiveness and toxicity of radiation dose escalation for locally advanced nasopharyngeal carcinoma (LA-NPC) in patients with local and/or regional residual lesion(s) after standard treatment. METHODS: From November 2011 to November 2020, 259 LA-NPC patients who had local and/or regional residual lesion(s) after induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1-74.25 Gy (median, 70.4 Gy). The boost doses were 4.0-18.0 Gy (median, 9 Gy), 1.8-2.0 Gy/fraction. RESULTS: For all patients, the 5-year local relapse-free survival was 90.2%, regional relapse-free survival was 89.1%, locoregional relapse-free survival (LRRFS) was 79.5%, distant metastasis-free survival (DMFS) was 87.9%, failure-free survival (FFS) was 69.0%, and overall survival (OS) was 86.3%. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma Epstein-Barr virus-deoxyribonucleic acid ≤ 500 versus > 500, T1-2 versus T3-4, N0-1 versus N2-3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002). CONCLUSION: Boost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study. TRIAL REGISTRATION:  Retrospectively registered.

Excessive intake of sugar: An accomplice of inflammation.

High sugar intake has long been recognized as a potential environmental risk factor for increased incidence of many non-communicable diseases, including obesity, cardiovascular disease, metabolic syndrome, and type 2 diabetes (T2D). Dietary sugars are mainly hexoses, including glucose, fructose, sucrose and High Fructose Corn Syrup (HFCS). These sugars are primarily absorbed in the gut as fructose and glucose. The consumption of high sugar beverages and processed foods has increased significantly over the past 30 years. Here, we summarize the effects of consuming high levels of dietary hexose on rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, inflammatory bowel disease (IBD) and low-grade chronic inflammation. Based on these reported findings, we emphasize that dietary sugars and mixed processed foods may be a key factor leading to the occurrence and aggravation of inflammation. We concluded that by revealing the roles that excessive intake of hexose has on the regulation of human inflammatory diseases are fundamental questions that need to be solved urgently. Moreover, close attention should also be paid to the combination of high glucose-mediated immune imbalance and tumor development, and strive to make substantial contributions to reverse tumor immune escape.

Experimental Phaeohyphomycosis of Curvularia lunata.

Originally considered to be a plant pathogen, reports of phaeohyphomycosis due to Curvularia lunata (C. lunata) in animals and humans are increasing. However, studies on the pathogenesis, virulence, and epidemiology of C. lunata have rarely been discussed. In the present study, BALB/c mice were experimentally inoculated with C. lunata suspension by different routes and the course of infection was evaluated. In addition, the in vitro antifungal susceptibility of C. lunata against six commonly used antifungals was evaluated using the microdilution method. Inoculation resulted in skin lesions in animals inoculated intraperitonially and subcutaneously. Infection was confirmed by both mycological and histopathologic examination. C. lunata spores and hyphae were detected in the histopathologic sections stained with hexamine silver staining. In addition, voriconazole (VRC) demonstrated greater activity against C. lunata when compared to the other antifungals, whereas fluconazole (FLC) was the least active antifungal with a minimum inhibitory concentration (MIC) range of 8-16 µg/mL. Further studies are necessary to understand the pathogenicity of C. lunata and uncover the mystery of this fungus.

Euphorfiatnoids A-I: Diterpenoids from the roots of Euphorbia fischeriana with cytotoxic effects.

Nine previously undescribed diterpenoids, euphorfiatnoids A-I, together with seven known diterpenoids, were isolated from the roots of wild Euphorbia fischeriana. Their structures were elucidated by the interpretation of HRESIMS, UV, and NMR data. Their configurations were determined by electronic circular dichroism (ECD) spectroscopy analysis and the structure of euphorfiatnoid A was confirmed by X-ray crystallography. To further understand the antitumor effects of E. fischeriana, we tested the cytotoxicity of these compounds against H460, HepG2, and MCF-7 cell lines in vitro using MTT assays. Euphorfiatnoid B exhibited the most promising inhibitory effect against H460 cells with an IC50 value of 9.97 µM. Euphorfiatnoid A and C also exhibited moderate cytotoxicity against HepG2 cells with IC50 values of 11.64 and 13.10 µM, respectively.

Highly Enantioselective Three-Component Povarov Reaction for Direct Construction of Azaspirocycles.

An asymmetric organocatalyzed three-component Povarov reaction to construct azaspirocycles has been developed. A chiral phosphoric acid OCF-CPA bearing o-CF3-aryl on the H8-BINOL-framework is highly efficient in the reaction. The reaction was carried out under mind conditions for synthesis of a range of azaspirocycles in high yields and high to excellent enantioselectivities, thus expending the substrate scope of the traditional Povarov reaction.

Exosomes from mmu_circ_0001052-modified adipose-derived stem cells promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway.

BACKGROUND: Diabetic foot ulcer (DFU) is a chronic infectious disease caused by diabetes mellitus (DM). Angiogenesis plays the decisive role in wound healing of DFU. Adipose-derived stem cells (ADSCs) can ameliorate angiogenesis in DFU by exosomes. This study aims to determine the mechanism of exosomes from mmu_circ_0001052-modified ADSCs in angiogenesis of DFU. METHODS: HUVECs were induced by high glucose and mice stimulated using STZ injection during high-fat feeding, which were treated with exosomes derived from mmu_circ_0001052-modified ADSCs. Real-time PCR determined the expression of gene and western blot determined protein levels. Proliferation, migration, apoptosis and angiogenesis of HUVECs were studied by MTT assay, transwell test, flow cytometry and tube formation experiment, respectively. Histological lesion of wound was determined by HE staining. RESULTS: The expression of circ_0001052 was upregulated in ADSCs and miR-106a-5p elevated in high glucose-induced HUVECs. Exosomal mmu_circ_0001052 significantly accelerated wound healing in mice with DFU. Also, exosomal mmu_circ_0001052 evoked the reduction of miR-106a-5p and the elevation of FGF4 in high glucose-induced HUVECs and wound tissue of DFU mice. Exosomal mmu_circ_0001052 was determined to sponge miR-106a-5p that targeted FGF4 in DFU. In high glucose-induced HUVECs, exosomal mmu_circ_0001052 inhibited apoptosis and miR-106a-5p expression, and meanwhile promoted proliferation, migration, angiogenesis and expressions of FGF4, VEGF and p-p38/p38, which were reversed by miR-106a-5p elevation. CONCLUSION: Mmu_circ_0001052 in ADSCs-derived exosomes promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway.

[Effects of Obstructive Sleep Apnea and Gender on Glomerular Filtration Rate in Hypertensive Population].

Objective To explore the associations of obstructive sleep apnea(OSA) and gender with estimated glomerular filtration rate(eGFR) in hypertensive populations.Methods From February 2005 to August 2010,2064 hypertensive patients who were treated in the Department of Hypertension Center underwent overnight polysomnographic monitoring.According to the apnea-hypopnea index(AHI),they were assigned into an hypertension combined with OSA group and a hypertension group.The clinical characteristics and sleep monitoring indicators were compared between different genders and between the two groups.Multivariate Logistic regression was employed to analyze the influencing factors of eGFR.Results Among the 2064 hypertensive patients,there were 1537 males(including 1221 patients with OSA) and 527 females(including 350 patients with OSA).The males had higher prevalence of OSA(χ2=36.631,P<0.001) and diastolic blood pressure(Z=-7.776,P<0.001) and lower eGFR(Z=-3.010,P=0.003) than the females.The males had higher AHI(Z=-8.727,P<0.001),apnea index(Z=-9.252,P<0.001),hypopnea index(HI)(Z=-4.868,P<0.001) than the females,and the lowest oxygen saturation(t=-3.325,P=0.001) was significantly lower in males than in females.The hypertension combined with OSA group showed lower eGFR than the hypertension group(Z=-27.434,P<0.001;Z=-18.762,P<0.001).HI was negatively correlated with eGFR in the male population(r=-0.006,P=0.017),and AHI and HI were negatively correlated eGFR in females(r=-0.108,P=0.013;r=-0.094,P=0.032).After adjustment,Logistic regression showed that OSA and oxygen desaturation index 4 were the risk factors for the reduction of eGFR in hypertensive patients in males and females,respectively(OR=1.383,95%CI=1.010-1.905,P=0.045;OR=1.013,95%CI=1.002-1.024,P=0.021).Conclusion OSA lowers the eGFR of hypertensive patients,and OSA and oxygen desaturation index are the risk factors for the decrease in eGFR in male and female hypertensive patients,respectively.

Mannose: A Sweet Option in the Treatment of Cancer and Inflammation.

As a natural sugar, mannose is a type of hexose that is abundant in many different types of fruits. Since mannose is rarely used for glycolysis in mammals, studies on the role of mannose have not attracted much attention. Glycosylation of specific proteins was thought to be the major function of mannose. Surprisingly, during the past few years, mannose was found to be effective in promoting immune tolerance and suppressing inflammatory diseases related to autoimmunity and allergy. Moreover importantly, mannose was also found to be efficient in suppressing tumors by suppressing glycolysis and enhancing chemotherapeutic agents. In this review, we summarize the recent studies of mannose on antitumor properties and anti-inflammatory characteristics. We emphasize that mannose could play a beneficial role in the treatment of a variety of diseases, including cancers and inflammatory diseases, and could be a novel therapeutic strategy that deserves continued evaluation.

Development and Validation of a Prognostic Model to Predict High-Risk Patients for Coronary Heart Disease in Snorers With Uncontrolled Hypertension.

Purpose: Snoring or obstructive sleep apnea, with or without uncontrolled hypertension, is common and significantly increases the risk of coronary heart disease (CHD). The aim of this study was to develop and validate a prognostic model to predict and identify high-risk patients for CHD among snorers with uncontrolled hypertension. Methods: Records from 1,822 snorers with uncontrolled hypertension were randomly divided into a training set (n = 1,275, 70%) and validation set (n = 547, 30%). Predictors for CHD were extracted to construct a nomogram model based on multivariate Cox regression analysis. We performed a single-split verification and 1,000 bootstraps resampling internal validation to assess the discrimination and consistency of the prediction model using area under the receiver operating characteristic curve (AUC) and calibration plots. Based on the linear predictors, a risk classifier for CHD could be set. Results: Age, waist circumference (WC), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) were extracted as the predictors to generate this nomogram model. The C-index was 0.720 (95% confidence interval 0.663-0.777) in the derivation cohort and 0.703 (0.630-0.776) in the validation cohort. The AUC was 0.757 (0.626-0.887), 0.739 (0.647-0.831), and 0.732 (0.665-0.799) in the training set and 0.689 (0.542-0.837), 0.701 (0.606-0.796), and 0.712 (0.615-0.808) in the validation set at 3, 5, and 8 years, respectively. The calibration plots showed acceptable consistency between the probability of CHD-free survival and the observed CHD-free survival in the training and validation sets. A total of more than 134 points in the nomogram can be used in the identification of high-risk patients for CHD among snorers with uncontrolled hypertension. Conclusion: We developed a CHD risk prediction model in snorers with uncontrolled hypertension, which includes age, WC, HDL-C, and LDL-C, and can help clinicians with early and quick identification of patients with a high risk for CHD.

Two New Xanthones from the Twigs of Calophyllum membranaceum and Their Anti-Inflammatory Activities in HESC Cells.

Two new xanthones, calmemxanthone A (1) and calmemxanthone B (2), along with eleven known compounds were isolated from the dried twigs of Calophyllum membranaceum Gardn. et Champ. The structures of compounds 1 and 2 were established by analysis of spectra and mass spectrometry data. The absolute configuration of compound 1 was confirmed by electronic circular dichroism (ECD) spectral analysis. The anti-inflammation action of these compounds were evaluated on lipopolysaccharide (LPS)-induced inflammatory damage to human endometrial stromal cells (HESCs), and the structure-activities of 1-13 were also discussed. Compound 10 presented the anti-inflammation action with an IC50 value of 20.3 µM, that might be relevant to the regulation of NF-κB signaling pathway via the suppression of TRIF, IKKα, and IκBα.

Role of Cytokines in Thymic Regulatory T Cell Generation: Overview and Updates.

CD4+CD25+Foxp3+ Regulatory (Treg) T cells are mainly generated within the thymus. However, the mechanism of thymic Treg cell (tTreg cell) generation remains to be fully revealed. Although the functions of TCR/CD28 co-stimulation have been widely accepted, the functions of cytokines in the generation of tTreg cells remain highly controversial. In this review, we summarize the existing studies on cytokine regulation of tTreg cell generation. By integrating the key findings of cytokines in tTreg cell generation, we have concluded that four members of γc family cytokines (IL-2, IL-4, IL-7 and IL-15), transforming growth factor ß (TGF-ß), and three members of TNF superfamily cytokines (GITRL, OX40L and TNF-α) play vitally important roles in regulating tTreg cell generation. We also point out all disputed points and highlight critical scientific questions that need to be addressed in the future.