The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in patients with chronic heart failure.

BACKGROUND: In this study, we evaluated the predictive utility of neutrophil percentage-to-albumin ratio (NPAR) for all-cause mortality in patients with chronic heart failure (CHF). METHODS: Patients diagnosed as CHF enrolled in this retrospective cohort study were from Beijing Chaoyang Hospital, capital medical university. Admission NPAR was calculated as neutrophil percentage divided by serum albumin. The endpoints of this study were defined as 90-day, 1-year and 2-year all-cause mortality. Multivariable Cox proportional hazard regression model was performed to confirm the association between NPAR and all-cause mortality. Receiver operating characteristics (ROC) curves were used to evaluate the ability for NPAR to predict all-cause mortality. RESULTS: The 90-day (P = 0.009), 1-year (P < 0.001) and 2-year (P < 0.001) all-cause mortality in 622 patients with CHF were increased as admission NPAR increased. Multivariable Cox regression analysis found the higher NPAR value was still independently associated with increased risk of 90-day (Group III versus Group I: HR, 95% CI: 2.21, 1.01-4.86, P trend = 0.038), 1-year (Group III versus Group I: HR, 95% CI:2.13, 1.30-3.49, P trend = 0.003), and 2-year all-cause mortality (Group III versus Group I: HR, 95% CI:2.06, 1.37-3.09, P trend = 0.001), after adjustments for several confounders. ROC curves revealed that NPAR had a better ability to predict all-cause mortality in patients with CHF, than either albumin or the neutrophil percentage alone. CONCLUSIONS: NPAR was independently correlated with 90-day, 1-year, and 2-year all-cause mortality in patients with CHF.

[Platelet-rich Plasma Induces M2 Macrophage Polarization via Regulating AMPK Singling Pathway].

OBJECTIVE: To investigate the role of platelet-rich plasma (PRP) in inducing the M2 macrophage polarization via regulating AMPK singling pathway. METHODS: The expressions of M1 marker CD11c and M2 marker CD206 in macrophages of blank control group, LPS group, LPS+PRP group, and LPS+PRP+Compound C group were detected by flow cytometry. Western blot was used to observe the effects of PRP on the expression of AMPK-mTOR signaling pathway-related proteins at different times (12 h, 18 h and 24 h) after LPS treatment. RNA interference technology was used to silence the expression of AMPK in macrophages, and the expression of TGF-ß protein was subsequently examined by Western blot. RESULTS: LPS significantly reduced the expression of CD206 and increased the expression of CD11c (P <0.05). After the addition of PRP, the expression of CD206 was significantly increased (P <0.05), while the expression of CD11c was significantly decreased (P <0.05). Compared with LPS group, PRP treatment significantly increased the expressions of p-AMPK and p-ULK1 proteins at 12 h, 18 h and 24 h, while significantly decreased the expression of p-mTOR protein (P <0.05). After the addition of AMPK inhibitor Compound C, the expression of CD206 was significantly reduced (P <0.05) and the expression of CD11c was significantly increased compared with LPS+PRP group (P <0.05). After silencing the expression of AMPK in macrophages, the promotion effect of PRP on TGF-ß was significantly reduced (P <0.05). CONCLUSION: PRP can stimulate the transformation of macrophages to M2 type via AMPK signalling pathway.

A new type of phosphate-based phosphor Na3CsMg7(PO4)6:Eu2+/Mn2+ with high quantum efficiency and high thermostability.

The Eu2+ ion, with the 4f75d1 electronic configuration, is one of the most important activated ions due to its symmetry-allowed 4f → 5d electron transition. Herein, we successfully prepared a new type of blue phosphor, Na3CsMg7(PO4)6:xEu2+ (NCMP:xEu2+), in which Eu2+ occupies the Na+ sites of the host lattice. Under 395 nm light excitation, a broad emission band from 410 to 550 nm can be seen, peaking at 458 nm, due to the 5d → 4f transition of Eu2+. Moreover, Eu2+ can be used as a sensitizer ion in an NCMP host. For co-doping phosphor NCMP:0.18Eu2+/0.4Mn2+, both Eu2+ and Mn2+ emission bands can be seen using 395 nm as the excitation wavelength for the occurrence of Eu2+ → Mn2+ charge transfer. The optimized concentration of Eu2+ for NCMP:xEu2+ is x = 0.18, with high internal (IQE) and external quantum efficiencies (EQE) of 66.4% and 22.8%. The luminescence of NCMP:0.18Eu2+ has high thermostability with 77.3% the intensity at 450 K compared to that at 300 K. Finally, a white illuminating lamp was produced using a 395 nm UV chip, blue phosphor NCMP:xEu2+, green phosphor (Sr,Ba)2SiO4:Eu2+ and red phosphor CaAlSiN3:Eu2+ with CIE coordinates of (0.378, 0.369), color temperature (CCT) of 3971 K, and color rendering index (Ra) of 79.8.

MiR-339 is a potential biomarker of coronary heart disease to aggravate oxidative stress through Nrf2/FOXO3 targeting Sirt2.

BACKGROUND: MicroRNA (miRNA) is a class of small-molecule RNA that can regulate gene expression at post-transcription level. It is involved in the genesis and development of multiple diseases. The aim of this paper was to explore the mechanisms of miR-339 in coronary heart disease (CHD). METHODS: In this study, we enrolled patients with CHD from Beijing Chaoyang Hospital and performed animal experiments on CHD rats. In vitro experiments, such as histopathologic assay, quantitative real-time PCR assay, luciferase reporter assay, western blotting assay, and immunofluorescence assay were carried out to characterize the contents and associations of miR-339, Nrf2, FOXO3, and Sirt2 in CHD samples and cells. In vivo model was also established on rats. RESULTS: In CHD rat, miR-339 was up-regulated compared with control group. The expression of miR-339 up-regulation increased oxidative stress in vitro model via suppression of Sirt2/Nrf2/FOXO3. However, down-regulation of miR-339 expression inhibited oxidative stress in vitro model via activation of Sirt2/Nrf2/FOXO3. The Sirt2 or Nrf2 inhibitor reduced the protective effect of miR-339 down-regulation on oxidative stress in vitro model. CONCLUSIONS: Down-regulation miR-339 may be the new targets to treat CHD through Nrf2/FOXO3 targeting Sirt2, and miR-339 may be a potential biomarker of CHD.

Preparation of biocompatible wound dressings with dual release of antibiotic and platelet-rich plasma for enhancing infected wound healing.

The ever-growing threats of bacterial infection and chronic wound healing have provoked an urgent need for novel antibacterial wound dressings. In this study, we developed a wound dressing for the treatment of infected wounds, which can reduce the inflammatory period (through the use of gentamycin sulfate (GS)) and enhance the granulation stage (through the addition of platelet-rich plasma (PRP)). Herein, the sustained antimicrobial CMC/GMs@GS/PRP wound dressings were developed by using gelatin microspheres (GMs) loading GS and PRP, covalent bonding to carboxymethyl chitosan (CMC). The prepared dressings exhibited high water uptake capability, appropriate porosity, excellent mechanical properties, sustain release of PRP and GS. Meanwhile, the wound dressing showed good biocompatibility and excellent antibacterial ability against Gram-negative and Gram-positive bacteria. Moreover, in vivo experiments further demonstrated that the prepared dressings could accelerate the healing process of E. coli and S. aureus-infected full-thickness wounds in vivo, reepithelialization, collagen deposition and angiogenesis. In addition, the treatment of CMC/GMs@GS/PRP wound dressing could reduce bacterial count, inhibit pro-inflammatory factors (TNF-α, IL-1ß and IL-6), and enhance anti-inflammatory factors (TGF-ß1). The findings of this study suggested that biocompatible wound dressings with dual release of GS and PRP have great potential in the treatment of chronic and infected wounds.

ß1-Adrenoceptor antibodies induce PPCM via inhibition of PGC-1α related pathway.

OBJECTIVES: Peripartum cardiomyopathy (PPCM) is a pregnancy-associated and life-threatening cardiac disease. However, the causes and pathogenesis are not fully understood. Accumulating studies show that cardiomyopathy often appears to be associated with elevated levels of ß1-adrenoceptor (ß1AR) antibodies, indicating a possible involvement of ß1AR antibodies in the development of PPCM. DESIGN: We injected the antigen peptide segment of the ß1AR into the postpartum Wistar rats to make the immune models and their cardiac function was detected by echocardiography. Also, the concentration of ß1AR antibodies and apoptosis rate of left ventricular myocytes was tested by SA-ELISA, TUNEL, HE staining, qRT-PCR and western blot methods. Finally, the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and its related proteins were examined by qRT-PCR and western blot methods. RESULTS: We found that the level of ß1AR antibodies in the serum was significantly increased and the postpartum rats exhibited symptoms of PPCM after autoimmunity. Moreover, the expression of peroxisome PGC-1α, which was a master regulator of mitochondrial metabolism, and its downstream transcript vascular endothelial growth factor (VEGF), was decreased in autoimmune perinatal rats. In addition, the expression of the apoptosis factor caspase 3 as well as the apoptosis rate of left ventricular myocytes was significantly increased. CONCLUSIONS: The results suggested that the symptoms of PPCM that appeared in autoimmune perinatal rats may be due to the increase of ß1AR antibodies, which inhibited the pathway associated with peroxisome PGC-1α.

Blood Group O Protect End-Stage Renal Disease Patients With Dialysis From Coronary Artery Disease.

OBJECTIVE: Our study aims to investigate the role of the ABO blood group in the development and severity of coronary artery disease (CAD) in end-stage renal disease (ESRD) patients with dialysis. METHODS: A total of 408 ESRD patients with dialysis between January 2010 and December 2020 were enrolled including 204 patients diagnosed with CAD undergoing coronary angiography for the first time, and baseline characteristics as well as Gensini score (GS) were collected. Logistic regression analysis and linear regression analysis were performed to evaluate the relation of ABO blood types to the risk and severity of CAD, respectively. RESULTS: Blood group O frequency was significantly low in dialysis ESRD patients with CAD (25 vs. 38.24%) compared with the non-CAD patients and multivariable logistic regression showed blood group O was negatively associated with the risk of CAD [adjusted odds ratio (OR) = 0.33, 95% CI = 0.19-0.60, p < 0.001] as well as the GS tertiles (adjusted OR = 0.23, 95% CI = 0.11-0.49, p < 0.001) compared with A blood group. Blood group A, B, and AB were positively associated with the high Gensini tertile compared with O blood group (adjusted OR = 4.26, 95% CI = 2.03-8.93, p < 0.001; adjusted OR = 2.39, 95% CI = 1.11-5.13, p < 0.05; adjusted OR = 4.33, 95% CI = 1.40-13.35, P < 0.05). Similarly, multivariable linear regression results revealed O blood type was negatively associated with the GS (ß = -26.129, 95% CI = -40.094 to -12.164, p < 0.001). CONCLUSION: This case-control study demonstrated that blood group O was a potential independent protective factor for the risk and severity of CAD in ESRD patients with dialysis.

Development of nanosilver doped carboxymethyl chitosan-polyamideamine alginate composite dressing for wound treatment.

Nowadays, treatment to the infected wounds caused by bacterial even multi-resistant bacterial strains and subsequently complete skin regeneration remain a critical clinical challenge. Herein, a novel multi-functional platform (Alg/1.0Ag@CMC-PAMAM/PRP) was prepared as wound dressings by mixing platelet rich plasma (PRP) with the sodium alginate (Alg) based dressing containing nano silver (Ag)-doped carboxymethyl chitosan grafted polyamideamine (Ag@CMC-PAMAM) cationic polymers. The present dressings exhibited high swelling, suitable water vapor transmission rate (WVTR), and good mechanical properties and degradability, as well as sustained release of PRP. Besides, the component of Ag@CMC-PAMAM nanoparticles endow them with excellent antibacterial performance, while the incorporation of PRP promotes the effect of anti-inflammatory and angiogenesis by up-regulating relative activity factor expression of TGF-ß1, CD31 and α-SMA and down-regulating the inflammatory-relative genes including TNF-α, IL-6 and IL-1ß, all of which promote the closure of wound and produce a superior healing effect to the commercial Aquacel Ag group. This work indicates that the prepared Alg/1.0Ag@CMC-PAMAM/PRP wound dressing is a promising biomaterial with synergistic effect of antibacterial property and wound healing.

Application of blood pre-albumin and NT-pro BNP levels in evaluating prognosis of elderly chronic heart failure patients.

Levels of blood pre-albumin (PA) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) in elderly patients with chronic heart failure (CHF) and their clinical value in prognosis evaluation were explored. A total of 410 elderly patients aged ≥65 years hospitalized for CHF were enrolled. The concentrations of blood PA and NT-pro BNP, routine blood test and biochemistry indicators were determined and color Doppler echocardiography was performed. Additionally, the patients were followed up after discharge, and based on the occurrence of major adverse cardiac events (MACE), they were divided into MACE group and non-MACE group. MACE group had an older age and a higher level of plasma NT-pro BNP than non-MACE group (77.82±6.57) years vs. (76.39±6.18) years, and (8,864.52±9,718.36) pg/ml vs. (4,165.62+6,437.28) pg/ml (P<0.05), and the left ventricular ejection fraction and serum PA level in MACE group were lower than those in non-MACE group (P<0.05). According to the results of multivariate regression analysis, serum PA [odds ratio (OR)=0.242, 95% confidence interval (CI)=0.137-0.406, P<0.001] and plasma NT-pro BNP (OR=1.847, 95% CI=1.024-3.158, P=0.036) were independent risk factors for the occurrence of cardiac events during follow-up. Decline in PA level and elevation in NT-pro BNP level have a strong correlation with poor prognosis of elderly CHF patients, and they can be used for clinically evaluating disease conditions, guiding treatment and improving prognosis.

ß1 adrenoceptor antibodies induce myocardial apoptosis via inhibiting PGC-1α-related pathway.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is life-threatening heart disease. However, the causes and pathogenesis of PPCM remain unclear. Previous studies found that ß1 adrenoceptor antibodies (ß1AA) had possible involvement in the development of PPCM. In the present study, we determined the potential relationship between PPCM and ß1AA, including the mechanism of ß1AA leading to PPCM. METHODS: We extracted the ß1AA from the postpartum Wistar rats that were injected by the antigen peptide segment of the ß1 adrenoceptor to produce PPCM. We tested the effects of ß1AA on H9C2 cell line by CCK-8, LDH, TUNEL, SA-ELISA, qRT-PCR, and western blot methods. Furthermore, PGC-1α was overexpressed to rescue the effect of ß1AA on H9C2 cells. RESULTS: We found that the extracted ß1AA induced apoptosis of cardiac myocytes of H9C2 cell line. Moreover, the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is a master regulator of mitochondrial metabolism, and its downstream transcript vascular endothelial growth factor (VEGF) got decreased in H9C2 cells after ß1AA treatment. In addition, the effect of ß1AA could be inhibited by atenolol, the antagonist of ß1 adrenoceptors (ß1AR) and imitated by isoprenaline, the agonist of ß1AR. Furthermore, overexpression of PGC-1α in the H9C2 cells rescued the apoptosis of cells and inhibitory expression of VEGF induced by ß1AA. CONCLUSIONS: Our results suggest that the symptoms of PPCM due to myocardial cell apoptosis induced by ß1AA inhibiting the PGC-1α-related pathway impairs mitochondrial energy metabolism. Therefore, our results uncover a previously unknown role of the ß1AA pathway in the etiology of PPCM and provide a novel potential target for the treatment of PPCM.

Epigenetic silencing of miR-335 induces migration by targeting insulin-like growth factor-1 receptor in multiple myeloma.

Multiple myeloma (MM) is a common hematological malignancy and remains incurable. MiRNA-335 is a classic tumor suppressor, yet its expression pattern and biological role in MM is unclear. The aim of the present study was to determine the expression pattern, biological role, and mechanism of miR-335 in MM. In this study, we found that miR-335 expression was decreased in MM. The promoter of miR-335 was also hypermethylated in MM. It was found that over-expression of miR-335 or 5-azacytidine treatment suppressed migration of MM cells and down-regulated the expression of IGF-1R. MiR-335 thus acts as a metastatic suppressor by targeting IGF-1R in MM. Moreover, aberrant promoter hyper-methylation is critical for miR-335 silencing in MM. We also found that miR-335 assisted in predicting both the prognosis and progression of disease in MM patients. Observations might offer a new complementary diagnostic and therapeutic target in MM.

MiR-19b and miR-20a suppress apoptosis, promote proliferation and induce tumorigenicity of multiple myeloma cells by targeting PTEN.

Multiple myeloma (MM) is a common hematological malignancy that is often associated with osteolytic lesions, anemia and renal impairment. Deregulation of miRNA has been implicated in the pathogenesis of MM. It was found in our study that miR-19b and miR-20a as members of crucial oncogene miR-17-92 cluster were differentially expressed between patients with MM and normal controls by genechip microarray, and this result was further confirmed in sera of patients with MM by qRT-PCR. The functional effect of miR-19b/20a was analyzed and results showed that miR-19b/20a promoted cell proliferation and migration, inhibited cell apoptosis and altered cell cycle in MM cells. PTEN protein expression was reduced after transfection of miR-19b/20a, suggesting that PTEN was a direct target of miR-19b/20a. In addition, over-expression of miR-19b/20a reversed the anti-proliferation and pro-apoptosis effect of PTEN in MM cells. Finally, our in vivo experiment demonstrated that lentivirus-mediated delivery of miR-20a promoted tumor growth in murine xenograft model of MM, which provide evidence that miR-20a inhibitor exerts therapeutic activity in preclinical models and supports a framework for the development of miR-19b/20a-based treatment strategies for MM patients.

Effects of a protective agent on freeze-dried platelet-rich plasma.

: Freeze-drying is an effective means of storing platelets. In this study, we investigated the effects of a protective agent on freeze-dried platelet-rich plasma (FD-PRP) after a 12-week preservation period. Platelet structure was measured by transmission electron microscopy (TEM), and the expression levels of procaspase activating compound (PAC)-1 and CD62P were measured by flow cytometry. The levels of transforming growth factor-beta (TGF-ß), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) were determined by ELISA. The effect of FD-PRP on cell proliferation was measured by cell counting. TEM revealed that most platelets were intact, and their internal structure was evident. The expression levels of the platelet activation marker CD62P in FD-PRP and fresh PRP were 36.83% ±â€Š8.21 and 35.47% ±â€Š4.11, respectively, without a significant difference (P > 0.05). The expression levels of PAC-1 in FD-PRP and fresh PRP were 3.23% ±â€Š0.49 and 2.83% ±â€Š0.44, respectively, without a significant difference (P > 0.05). Upon activation of FD-PRP and fresh PRP by thrombin, the levels of TGF-ß, PDGF and VEGF were not significantly decreased in FD-PRP. Moreover, FD-PRP promoted cell proliferation in a manner similar to that of fresh PRP. The protective agent maintained the biological activity of FD-PRP after a 12-week preservation period.

Effect of premature birth on long-term systolic blood pressure variability in women.

OBJECTIVE: To investigate the effect of premature birth (PTB) on long-term systolic blood pressure (SBP) variability (SBPV) in women. METHODS: A total of 1974 pregnant women were divided into PTB group and non-PTB (NPTB) group. The SBP standard deviation (SSD) was calculated by four annual SBP values measured in 2006-2007, 2008-2009, 2010-2011, and 2012-2013. SBP coefficient of variation (SCV) was calculated by dividing SSD with mean SBP. Multivariate logistic regression analysis was used to analyze the influence of PTB on long-time SSD and SCV in women. RESULTS: SSD and SCV of the PTB group (10.95 mm Hg and 9.05%, respectively) were higher than those of the NPTB group (9.81 mm Hg and 8.23%, respectively), but there were no significant differences (p>0.05). The number of patients with SSD >9.87 mm Hg and SCV >8.28% in the PTB and NPTB groups was 57 (51.40%) and 62 (55.90%) and 747 (40.10%) and 841 (45.10%), respectively. The number of patients with SSD >9.87 mm Hg and SCV >8.28% in the PTB group was significantly higher than that in the NPTB group (p<0.05). Multiple logistic regression analysis showed that after adjusting other risk factors, the PTB group was at a risk of SSD and SCV elevations with OR values of 1.60 (95% CI: 1.06-2.40) and 1.64 (95% CI: 1.10-2.45), respectively. CONCLUSION: PTB is a risk factor of long-time SBPV in women, which might be a potential reason for cardiovascular events. Pregnancy may be an important opportunity for early identification of women at an increased risk of cardiovascular disease later in life.

Preliminary study of microRNA-126 as a novel therapeutic target for primary hypertension.

The present study aimed to explore microRNA-126 (miR-126) as a novel therapeutic target for primary hypertension. The lentiviral vector containing human immunodeficiency virus 1 (HIV­1), the miR­126 gene knockdown viral vector (lenti-miR-126-KD), and control lentiviral vector (lenti­scramble­miR) were constructed. Spontaneously hypertensive rats were randomly divided into 4 groups, which received a high dose of lenti­miR­126­KD (1x108, n=5), low dose of lenti­miR­126­KD (1x107, n=6), scramble­miR (5x107, n=6), and PBS (n=6). Lentiviral vectors were injected into the tail vein. Data on the systolic blood pressure, diastolic pressure, mean arterial pressure, and heart rate were collected weekly. After 8 weeks of virus administration, the distribution of lentiviral vectors in different tissues was observed by fluorescence microscopy. Picric acid Sirius red and H&E staining were used to observe the target organ damage, and the ELISA kit was used to determine the serum nitric oxide (NO) content. The lentiviral vector was found to be constructed successfully. Eight weeks after the lentiviral vector injection, green fluorescent protein was observed in different tissues in each group. The blood pressure and heart rate were not significantly altered after lentiviral vector injection (P>0.05). No significant differences in the heart­to­body weight ratio among the four groups were observed (P=0.23). Picric acid Sirius red and H&E staining revealed that there was no significant difference in morphology among the four groups. No significant difference in the serum NO level among the four groups was noted (P=0.23). The miR­126 gene knockdown lentiviral vector was constructed successfully. No significant antihypertensive effect was observed by the knockdown of miR­126 for the treatment of primary hypertension. The target organs were not protected significantly after the treatment. The increased level of miR­126 expression in hypertensive patients may be due to a compensatory mechanism.

Enzymic degradation of hydroxyethyl cellulose and analysis of the substitution pattern along the polysaccharide chain.

The enzymatic degradation behavior of hydroxyethyl cellulose (HEC) samples with different molar substitutions (MS) values was investigated. The changes in the molecular structure of HEC treated with enzymatic approach in comparison to the native HEC were studied through nuclear magnetic resonance (NMR), fourier transform infrared spectra (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques and kinetics of degradation was studied by viscometry. The cleavage of HEC chains could be observed from FTIR and kinetics results. Moreover, reduce in molecular weight (Mw) of polymer and liberated glucose concentration was investigated by gel permeation chromatography (GPC) analysis during enzymatic degradation. And all these results indicated that HEC with lower MS is more susceptible to degrade and provided a better understanding of the mechanism operating during enzymatic hydrolysis of HEC by cellulases. Furthermore, by complete degradation and quantification of liberated glucose, the substitution index (SI) and the distribution of substituents along the HEC chain were investigated. The results suggested that the HEC samples differed in hydroxyethyl molar substitutions (MS) and possible distribution of the hydroxyethyl groups. Impressively, our efforts established a facile analytical method for the elucidation of the distribution of substituents along the HEC chain.

Equol Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice by Inhibiting Endoplasmic Reticulum Stress via Activation of Nrf2 in Endothelial Cells.

The development of atherosclerosis is closely related to excessive endoplasmic reticulum stress (ERs). Equol reportedly protects against cardiovascular disease; however, the underlying mechanism for this protection remains unknown. Herein, the mechanisms contributing to the atheroprotective effect of equol were addressed using apolipoprotein E knockout (apoE-/-) mice fed a high-fat diet (HFD) with or without equol. Equol intervention reduced atherosclerotic lesions in the aorta in HFD-fed apoE-/- mice. Plasma lipid analysis showed that equol intervention reduced triglycerides, total cholesterol and LDL-cholesterol and increased HDL-cholesterol. Additionally, equol administration decreased lipid accumulation in the liver. Simultaneously, equol treatment inhibited cell apoptosis induced by t-BHP and thapsigargin in human umbilical vein endothelial cells (HUVECs). Furthermore, equol treatment attenuated palmitate, t-BHP or thapsigargin-induced upregulation of ER stress markers, including p-PERK, p-eIF2α, GRP78, ATF6 and CHOP proteins expression. The same tendency was also observed in aortic lysates in apoE-/- mice fed with equol plus HFD compared with HFD alone. Moreover, equol treatment dose dependently activated the Nrf2 signaling pathway under oxidative stress. Additionally, elevation of Nrf2 induction was found in aortic lysates in apoE-/- mice fed with a HFD diet containing equol compared with a HFD diet without equol. Importantly, Nrf2 siRNA interference induced CHOP and attenuated the effect of equol to inhibit t-BHP mediated CHOP induction, furthermore, abrogated cell apoptosis induced by t-BHP, suggesting a role for Nrf2 in the protective effect of equol in HUVECs. Collectively, these findings implicate that the improvement of atherosclerosis by equol through attenuation of ER stress is mediated, at least in part, by activating the Nrf2 signaling pathway.

Long non-coding RNA HULC as a novel serum biomarker for diagnosis and prognosis prediction of gastric cancer.

Long non-coding RNAs (lncRNAs) have recently emerged as vital players in tumor biology with potential value in cancer diagnosis, prognosis, and therapeutics. The lncRNA HULC (highly up-regulated in liver cancer) is increased in many malignancies, yet its serum expression profile and clinical value in gastric cancer (GC) patients remain unclear. Quantitative real-time polymerase chain reaction (RT-qPCR) for large-scale analysis of the serum expression of HULC in GC patients reliably detected circulating HULC and revealed that it is upregulated in GC patients. A high serum HULC level correlated with tumor size, lymph node metastasis, distant metastasis, tumor-node-metastasis stage, and H. pylori infection. The area under the ROC curve for HULC was up to 0.888, which was higher than that for CEA (0.694) and CA72-4 (0.514). Follow-up detection and Kaplan-Meier curve analysis revealed HULC is a good predictor of GC prognosis. Our present study indicates that circulating HULC may represent a novel serum tumor marker for early diagnosis and monitoring progression and prognosis of GC.

Ampelopsin protects endothelial cells from hyperglycemia-induced oxidative damage by inducing autophagy via the AMPK signaling pathway.

Diabetic angiopathy is a major diabetes-specific complication that often begins with endothelial dysfunction induced by hyperglycemia; however, the pathological mechanisms of this progression remain unclear. Ampelopsin is a natural flavonol that has strong antioxidant activity, but little information is available regarding its antidiabetic effect. This study focused on the effect of ampelopsin on hyperglycemia-induced oxidative damage and the underlying mechanism of this effect in human umbilical vein endothelial cells (HUVECs). We found that hyperglycemia impaired autophagy in HUVECs through the inhibition of AMP-activated protein kinase (AMPK), which directly led to endothelial cell damage. Ampelopsin significantly attenuated the detrimental effect of hyperglycemia-induced cell dysfunction in a concentration-dependent manner in HUVECs. Ampelopsin significantly upregulated LC3-II, Beclin1, and Atg5 protein levels but downregulated p62 protein levels in HUVECs. Transmission electron microscopy and confocal microscopy indicated that ampelopsin notably induced autophagosomes and LC3-II dots, respectively. Additionally, the autophagy-specific inhibitor 3-MA, as well as Atg5 and Beclin1 siRNA pretreatment, markedly attenuated ampelopsin-induced autophagy, which subsequently abolished the protective effect of ampelopsin against hyperglycemia in HUVECs. Moreover, ampelopsin also increased AMPK activity and inhibited mTOR (mammalian target of rapamycin) complex activation. Ampelopsin-induced autophagy was attenuated by the AMPK antagonist compound C but strengthened by the AMPK agonist AICAR (5-minoimidazole-4-carboxamide ribonucleotide). Furthermore, AMPK siRNA transfection eliminated ampelopsin's alleviation of cell injury induced by hyperglycemia. The protective effect of ampelopsin against hyperglycemia-induced cell damage, which functions by targeting autophagy via AMPK activation, makes it a promising pharmacological treatment for type-2 diabetes.

Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway.

Insulin resistance in skeletal muscle is a key feature in the pathogenesis of type 2 diabetes (T2D) that often manifests early in its development. Pharmaceutical and dietary strategies have targeted insulin resistance to control T2D, and many natural products with excellent pharmacological properties are good candidates for the control or prevention of T2D. Dihydromyricetin (DHM) is a natural flavonol which provides a wide range of health benefits including anti-inflammatory and anti-tumor effects. However, little information is available regarding the effects of DHM on skeletal muscle insulin sensitivity as well as the underlying mechanisms. In the present study, we found that DHM activated insulin signaling and increased glucose uptake in skeletal muscle in vitro and in vivo. The expression of light chain 3, the degradation of sequestosome 1, and the formation of autophagosomes were also upregulated by DHM. DHM-induced insulin sensitivity improvement was significantly abolished in the presence of 3-methyladenine, bafilomycin A1, or Atg5 siRNA in C2C12 myotubes. Furthermore, DHM increased the levels of phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), and Sirt3 in skeletal muscle in vitro and in vivo. Autophagy was inhibited in the presence of Sirt3 siRNA in C2C12 myotubes and in skeletal muscles from Sirt3-/- mice. Additionally, PGC-1α or AMPK siRNA transfection attenuated DHM-induced Sirt3 expression, thereby abrogating DHM-induced autophagy in C2C12 myotubes. In conclusion, DHM improved skeletal muscle insulin sensitivity by partially inducing autophagy via activation of the AMPK-PGC-1α-Sirt3 signaling pathway.