[Effect of Gegen Qinlian Decoction on cardiac diastolic function of diabetic mice with damp-heat syndrome].

This study was designed to explore the effect and mechanism of Gegen Qinlian Decoction(GQD) on cardiac function of diabetic mice with damp-heat syndrome. The db/db diabetic mice were exposed to the damp-heat environment test chamber for inducing the damp-heat syndrome. Forty-eight six-week-old db/db mice were randomly divided into six groups, namely the db/db diabetic model group, db/db diabetic mouse with damp-heat syndrome(db/db-dh) group, db/db diabetic mouse with damp-heat syndrome treated with low-dose GQD(db/db-dh+GQD-L) group, db/db-dh+GQD-M(medium-dose) group, db/db-dh+GQD-H(high-dose) group, and db/db-dh+lipro(liprostatin-1, the inhibitor of ferroptosis) group, with eight six-week-old db/m mice classified into the control group. The results showed that mice presented with the damp-heat syndrome after exposure to the "high-fat diet" and "damp-heat environment", manifested as the elevated fasting blood glucose, reduced food intake, low urine output, diarrhea, listlessness, loose and coarse hair, and dark yellow and lusterless fur. However, the intragastric administration of the high-dose GQD for 10 weeks ameliorated the above-mentioned symptoms, inhibited myocardial hypertrophy and fibrosis, and improved the cardiac diastolic function of db/db-dh mice. qPCR suggested that GQD regulated the expression of ferroptosis-related genes, weakened the lipid peroxidation in the myocardium, and up-regulated glutathione peroxidase 4(GPX4) expression in comparison with those in the db/db-dh group. At the same time, the ferroptosis inhibitor liprostatin-1 significantly improved the cardiac function and reversed the cardiac remodeling of db/db-dh mice. It can be concluded that the damp-heat syndrome may aggravate myocardial ferroptosis and accelerate cardiac remodeling of db/db mice, thus leading to diastolic dysfunction. GQD is able to improve cardiac remodeling and diastolic function in diabetic mice with damp-heat syndrome, which may be related to its inhibition of myocardial ferroptosis.

Spermidine-enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway.

BACKGROUND AND PURPOSE: Spermidine, a natural polyamine, is abundant in mammalian cells and is involved in cell growth, proliferation, and regeneration. Recently, oral spermidine supplements were cardioprotective in age-related cardiac dysfunction, through enhancing autophagic flux. However, the effect of spermidine on myocardial injury and cardiac dysfunction following myocardial infarction (MI) remains unknown. EXPERIMENTAL APPROACH: We determined the effects of spermidine in a model of MI, Sprague-Dawley rats with permanent ligation of the left anterior descending artery, and in cultured neonatal rat cardiomyocytes (NRCs) exposed to angiotensin II (Ang II). Cardiac function in vivo was assessed with echocardiography. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots. KEY RESULTS: Spermidine improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with angiotensin II. In rats post-MI, spermidine reduced infarct size, improved cardiac function, and attenuated myocardial hypertrophy. Spermidine also suppressed the oxidative damage and inflammatory cytokines induced by MI. Moreover, spermidine enhanced autophagic flux and decreased apoptosis both in vitro and in vivo. The protective effects of spermidine on cardiomyocyte apoptosis and cardiac dysfunction were abolished by the autophagy inhibitor chloroquine, indicating that spermidine exerted cardioprotective effects at least partly through promoting autophagic flux, by activating the AMPK/mTOR signalling pathway. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that spermidine improved MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.

Heat shock protein 70: A promising therapeutic target for myocardial ischemia-reperfusion injury.

Acute myocardial infarction is a major cause of death worldwide. The most important therapy for limiting ischemic injury and infarct size is timely and efficient myocardial reperfusion treatment, which may instead induce cardiomyocyte necrosis due to myocardial ischemia-reperfusion (I/R) injury. Heat shock protein 70 (HSP70), a stress-inducible protein, is overexpressed during myocardial I/R. The induced HSP70 is shown to regulate several intracellular proteins (e.g., transcription factors, enzymes, and apoptosis-related proteins) and signaling pathways (e.g., c-Jun N-terminal kinase pathway and extracellular-signal-regulated kinase 1/2 pathway), forming a complicated network that contributes to reducing reactive oxygen species accumulation, improving calcium homeostasis, inhibiting cellular apoptosis, thereby enhancing the stress adaption of myocardium to I/R injury. In addition, the extracellular HSP70, which is released from injured cardiomyocytes during I/R, acts as a proinflammatory mediator that results in cell death, while the intracellular HSP70 exerts antiinflammatory effects by suppressing proinflammatory signaling pathways. Notably, HSP70 is induced and contributes to the cardioprotection in several types of preconditioning and postconditioning. Meanwhile, it is shown that the cardioprotective effectiveness of preconditioning-induced HSP70 (e.g., hyperthermia preconditioning-induced HSP70) can be impaired by certain pathological conditions, such as hyperlipidemia and hyperglycemia. Thus, we highlight the widespread cardioprotective involvement of HSP70 in preconditioning and postconditioning and elucidate how HSP70-mediated cardioprotection is impaired in these pathological conditions. Furthermore, several therapeutic potentials of HSP70 against myocardial I/R injury and potential directions for future studies are also provided in this review.

Electroacupuncture Preconditioning Improves Myocardial Infarction Injury via Enhancing AMPK-Dependent Autophagy in Rats.

BACKGROUND: Electroacupuncture (EA) pretreatment plays a protective role in myocardial infarction injury. However, the mechanism of electroacupuncture remains unknown. The aim of this study was to confirm the protective effects of electroacupuncture (EA) on myocardial infarction injury and the possible mechanism. METHODS: Sprague-Dawley (SD) rats, used to serve as acute myocardial infarction (AMI) model, were divided into sham group, model (M) group, M+EA group, AMPK inhibitor Compound C (M+EA+CC), and AMPK inhibitor solvent control (M+EA+DMSO) group, respectively. Rats in EA group were pretreated with EA and those in M+EA+CC group with intravenous AMPK inhibitor Compound C. The myocardial morphological changes and infarct size were observed through HE staining and TTC staining, and the concentrations of CK-MB and LDH were detected using ELISA kits. Transmission electron microscopy was employed to observe the autophagosome formation, and the AMPK-dependent autophagy-related protein expression was detected by immunohistochemistry and western blot. RESULTS: EA could alleviate myocardial infarction injury and decrease the concentrations of CK-MB and LDH. Transmission electron microscopy showed that EA could also regulate the AMPK-dependent autophagosome formation and the AMPK-dependent autophagy-related protein expression. AMPK inhibitor Compound C could impair the effect of EA through regulating the concentrations of CK-MB and LDH, autophagosome formation, and autophagy-related protein expression. CONCLUSION: These results indicated that electroacupuncture could improve myocardial infarction injury and induce autophagy, and AMPK-dependent autophagy might be involved in this process.

The Role of Peroxisome Proliferator-Activated Receptor γ in Mediating Cardioprotection Against Ischemia/Reperfusion Injury.

Myocardial infarction (MI) is a serious cardiovascular disease resulting in high rates of morbidity and mortality. Although advances have been made in restoring myocardial perfusion in ischemic areas, decreases in cardiomyocyte death and infarct size are still limited, attributing to myocardial ischemia/reperfusion (I/R) injury. It is necessary to develop therapies to restrict myocardial I/R injury and protect cardiomyocytes against further damage after MI. Many studies have suggested that peroxisome proliferator-activated receptor γ (PPARγ), a ligand-inducible nuclear receptor that predominantly regulates glucose and lipid metabolism, is a promising therapeutic target for ameliorating myocardial I/R injury. Thus, this review focuses on the role of PPARγ in cardioprotection during myocardial I/R. The cardioprotective effects of PPARγ, including attenuating oxidative stress, inhibiting inflammatory responses, improving glucose and lipid metabolism, and antagonizing apoptosis, are described. Additionally, the underlying mechanisms of cardioprotective effects of PPARγ, such as regulating the expression of target genes, influencing other transcription factors, and modulating kinase signaling pathways, are further discussed.

Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress.

AIM: Sulforaphane (SFN), a natural dietary isothiocyanate, is found to exert beneficial effects for cardiovascular diseases. This study aimed to investigate the mechanisms underlying the protective effects of SFN in a model of myocardial hypoxia/reoxygenation (H/R) injury in vitro. METHODS: Cultured neonatal rat cardiomyocytes pretreated with SFN were subjected to 3-h hypoxia followed by 3-h reoxygenation. Cell viability and apoptosis were detected. Caspase-3 activity and mitochondrial membrane potential (ΔΨm) was measured. The expression of ER stress-related apoptotic proteins were analyzed with Western blot analyses. Silent information regulator 1 (SIRT1) activity was determined with SIRT1 deacetylase fluorometric assay kit. RESULTS: SFN (0.1-5 µmol/L) dose-dependently improved the viability of cardiomyocytes, diminished apoptotic cells and suppressed caspase-3 activity. Meanwhile, SFN significantly alleviated the damage of ΔΨm and decreased the expression of ER stress-related apoptosis proteins (GRP78, CHOP and caspase-12), elevating the expression of SIRT1 and Bcl-2/Bax ratio in the cardiomyocytes. Co-treatment of the cardiomyocytes with the SIRT1-specific inhibitor Ex-527 (1 µmol/L) blocked the SFN-induced cardioprotective effects. CONCLUSION: SFN prevents cardiomyocytes from H/R injury in vitro most likely via activating SIRT1 pathway and subsequently inhibiting the ER stress-dependent apoptosis.

[Distribution Characteristics of Methanogens in Urban Sewer System].

A study was conducted through a 1200 m-PVC-pipe-reactor, which was used to simulate the urban sewer system. Gas chromatography, liquid chromatography and 454 high-throughput sequencing were utilized to study the variation of substrates during the methanogenic process and the distribution characteristics of methanogens in the sewer system. The results showed that the concentration of methane increased along the sewer system, which illustrated that methanogens existed in the sewer network. The methanogens mainly contained Methanosarcina, Euryarchaeota_unclassified and Methanobacteriaceae_unclassified. The distinct succession which Euryarchaeota_unclassified replaced Methanosarcina to be the first dominant microbial genus between 800-1000 m of the sewer system. Formic acid, methanol, methylamine, acetic acid and hydrogen were available substrates for methanogens. Among these substrates, acetic acid was the primary substrate for methanogen. The variation trends of these substrates were first increasing and then decreasing along the length of the sewer system, which led to the succession phenomenon of methanogens in the sewer system.

[Changes in serum level of carboxy-terminal telopeptide of type I collagen in patients with coronary heart disease].

OBJECTIVE: To investigate the serum level of carboxy-terminal telopeptide of type I collagen (ICTP) and explore its correlation with MMP-2 and MMP-9 in patients with coronary artery disease (CHD). METHODS: A total of 103 CHD patients treated in our hospital between October, 2013 and May, 2014 were enrolled, including 39 with stable angina pectoris (SAP), 39 with unstable angina (UA), and 25 with acute myocardial infarction (AMI), with 38 non-CHD volunteers as the control group. The serum levels of ICTP, MMP-2, and MMP-9 were detected in all the subjects using enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant difference in serum levels of MMP-2, MMP-9, or ICTP was found between the control and SAP groups or between UA and AMI groups (P>0.05), but the latter two groups had significantly higher serum levels of MMP-2, MMP-9, and ICTP than the former two groups (P<0.05). Serum ICTP level was found to negatively correlated with the fibrotic area and positively with the lipid component in the plaques (P<0.05). Regression analysis revealed significant positive correlations of serum ICTP with MMP-2 and MMP-9 (P<0.05). CONCLUSION: An elevated serum ICTP level is indicative of the presence of unstable plaques in CHD patients. Serum ICTP is more strongly correlated with MMP-2 than with MMP-9, and can be used as a non-invasive marker for assessing vulnerable plaques in patients with acute coronary syndrome.

Molecularly targeted gemcitabine-loaded nanoparticulate system towards the treatment of EGFR overexpressing lung cancer.

Molecularly targeted therapy emerged as a novel therapeutic strategy in the treatment of multiple cancers. In the present study, we have developed gemcitabine (GEM)-loaded cetuximab (CET) surface modified poly(lactic) acid (PLA) nanoparticles (NP) (CET-GEM/PLA NP) to target to epidermal growth factor receptor (EGFR) overexpressing non-small cell lung cancer (A549) cells. The resultant CET-GEM/PLA NP showed a very uniform particle size of∼120 nm and spherical morphology. It exhibited a pH-dependent controlled release pattern. A sustained release of drug in the physiological conditions and faster release in tumor pH will greatly improve the chemotherapeutic efficiency of therapeutic system. Higher or enhanced cellular uptake of CET-GEM/PLA NP in A549 cancer cells clearly indicates the EGFR-mediated receptor based active targeting. Nearly, a two-fold increase in fluorescent intensity was observed for CET-GEM/PLA NP comparing to that of non-targeted NP in the cancer cells. EGFR-mediated internalization of the targeted NP was further confirmed by the confocal microscopy. MTT assay clearly showed the enhanced cell killing effect of CET-conjugated NP due to the selective delivery of GEM to the EGFR over expressing cancer cells. Finally, comparing to the non-targeted NP, CET-GEM/PLA NP showed greater level of cell apoptosis (early and late apoptosis∼40%). Our results showed that antibody conjugation on the surface of NP could be a potential treatment strategy for EGFR over expressing cancer cells. This suggests that CET-GEM/PLA NP could be potentially used for the treatment of NSCLC (lung cancers).

[Variation of different carbon sources in the sewage treatment process].

The biodegradability and speciation of organics were studied through long-term analysis of A2/O treatment. The majority of the organic matters were particle organics which accounted for 61% of the total organics. The proportions of rapidly degradable, slowly degradable and refractory organics were 15. 8% , 54. 2% and 30% respectively. Rapidly biodegradable organics were mainly dissolved organics while slowly biodegradable organics were particle organics. The variation of these two kinds of carbon sources was analyzed during the treatment process. It was noted that microbial hydrolysis fermentation took place in the anaerobic and anoxic tanks, which led to the transformation of slowly biodegradable organics and the anaerobic tank had the highest transformation rate. The transformation and utilization of rapidly/slowly biodegradable organics were analyzed through calculation. The results showed that the transformation efficiency of slowly biodegradable organics in the anaerobic and anoxic tanks in two hours was 33% and 20%, respectively. Furthermore, the amount and species of aliphatic acid increased in the anaerobic and anoxic tanks comparing with raw water.

Cutaneous metastasis from pancreatic cancer: A case report and systematic review of the literature.

Cutaneous metastasis from pancreatic cancer is uncommon, therefore, the outcome of this progression has rarely been investigated. The aim of the present report was to evaluate the clinical characteristics of patients exhibiting cutaneous metastasis from pancreatic cancer. Thus, the current report presents a rare case of cutaneous metastatic disease from pancreatic cancer and describes a systematic review of the literature. A total of 54 articles comprising 63 cases were included for analysis. The relevant clinical and pathological characteristics, as well as the treatment strategies and survival outcomes of this rare disease presentation were reviewed. The average patient was was aged 63.9 years and males constituted a marginally greater proportion of the cohort (61.9%). The predominant manifestation of the cutaneous metastasis was a nodule or mass (73%) and the most common site of the skin lesion was non-umbilicus rather than umbilicus. The majority (66.7%) of the skin lesions were singular, particularly in patients exhibiting Sister Mary Joseph's nodule (90%). A wide range of histological subtypes presented, with a predominance of adenocarcinoma (84.1%). Of the cases that specified the tumor differentiation grade, 78.2% were moderately or poorly differentiated. Immunohistochemistry revealed that cytokeratin (CK)20-negative, and CK7-, CK19- and carbohydrate antigen (CA)19-9-positive were specific diagnostic markers for pancreatic cancer. Distal metastases, excluding the skin, were observed in 68.3% of patients and the median survival period was 5 months. Treatment strategies including surgery, radiation, chemotherapy or a combination improved survival time from 3.0 to 8.3 months. Cutaneous metastasis from pancreatic cancer is a rare finding, often providing the only external indication of an internal malignancy and, therefore, should be considered in the differential diagnosis of skin lesions. Metastasis to the skin indicates a widespread, general dissemination and a poor prognosis. A combination of surgery, radiotherapy and chemotherapy appears to result in improved survival rates.

[Carvacrol pretreatment attenuates myocardial oxidative stress and apoptosis following myocardial ischemia-reperfusion in mice].

OBJECTIVE: To investigate the effect of carvacrol pretreatment on myocardial ischemia-reperfusion (I/R) injury and its underlying mechanisms. METHODS: Wild-type male C57 BL/6 mice were randomized into 5 groups (n=13), namely the sham-operated group, vehicle (DMSO in saline)+ I/R group, carvacrol (20 mg/kg) + I/R group, carvacrol (40 mg/kg) + I/R group, and carvacrol (60 mg/kg) + I/R group. The mouse models of myocardial I/R injury were established by a 45-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion for 2 h. Carvacrol or vehicle was administered intravenously 15 min before LAD occlusion. After reperfusion, the mice were examined for myocardial oxidative stress level and apoptosis rate. RESULTS: Compared with the vehicle group, the 3 carvacrol-pretreated groups showed significantly reduced myocardial infarct size, oxidative stress level and cardiac myocyte apoptosis rate (P<0.01). CONCLUSION: Carvacrol can protect against myocardial I/R injury by inhibiting myocardial oxidative stress and apoptosis in mice.

Incorporation of liquid-like multiwalled carbon nanotubes into an epoxy matrix by solvent-free processing.

Covalent attachment of 2,2'-(ethylenedioxy)-diethylamine to multiwalled carbon nanotubes (MWCNTs) produced amino-functionalized MWCNTs which behaved like liquids at ambient temperature. These liquid-like MWCNTs (l-MWCNTs) could be homogeneously dispersed and chemically embedded in an epoxy matrix by solvent-free processing. In contrast, solid MWCNTs (s-MWCNTs) functionalized by 1,8-diaminooctane were poorly dispersed in epoxy although they possess chemical structures and functionalization comparable to l-MWCNTs. An epoxy composite filled with pristine MWCNTs (p-MWCNTs) was also fabricated in the absence of a solvent at the same loading for comparison. The molecular level coupling of l-MWCNTs and epoxy provided significant improvements in overall mechanical properties relative to those composites containing p-MWCNTs and s-MWCNTs. The Young's modulus, storage modulus, tensile strength, failure strain and toughness of neat epoxy were increased by 28.4, 23.8, 22.9, 24.1 and 66.1%, respectively, by adding 0.5 wt% of l-MWCNTs. Thus, functionalized carbon nanotubes in liquid form contributed to better dispersion and superior interfacial bonding with the epoxy matrix, thereby facilitating greater mechanical reinforcement efficiency.