Autophagy/ferroptosis in colorectal cancer: Carcinogenic view and nanoparticle-mediated cell death regulation.

The cell death mechanisms have a long history of being evaluated in diseases and pathological events. The ability of triggering cell death is considered to be a promising strategy in cancer therapy, but some mechanisms have dual functions in cancer, requiring more elucidation of underlying factors. Colorectal cancer (CRC) is a disease and malignant condition of colon and rectal that causes high mortality and morbidity. The autophagy targeting in CRC is therapeutic importance and this cell death mechanism can interact with apoptosis in inhibiting or increasing apoptosis. Autophagy has interaction with ferroptosis as another cell death pathway in CRC and can accelerate ferroptosis in suppressing growth and invasion. The dysregulation of autophagy affects the drug resistance in CRC and pro-survival autophagy can induce drug resistance. Therefore, inhibition of protective autophagy enhances chemosensitivity in CRC cells. Moreover, autophagy displays interaction with metastasis and EMT as a potent regulator of invasion in CRC cells. The same is true for ferroptosis, but the difference is that function of ferroptosis is determined and it can reduce viability. The lack of ferroptosis can cause development of chemoresistance in CRC cells and this cell death mechanism is regulated by various pathways and mechanisms that autophagy is among them. Therefore, current review paper provides a state-of-art analysis of autophagy, ferroptosis and their crosstalk in CRC. The nanoparticle-mediated regulation of cell death mechanisms in CRC causes changes in progression. The stimulation of ferroptosis and control of autophagy (induction or inhibition) by nanoparticles can impair CRC progression. The engineering part of nanoparticle synthesis to control autophagy and ferroptosis in CRC still requires more attention.

[Down-regulation of miR-488 targeting to promote Jag1 expression inhibits hypoxia-reoxygenation myocardial H9c2 cell damage].

OBJECTIVE: To study the effect of down-regulating miR-488 targeting Jag1 on the injury of hypoxia-reoxygenation myocardial H9c2 cells. METHODS: A hypoxic-reoxygenated myocardial H9c2 cell injury model was constructed. miR-488 inhibitor was used to transfect the cells. CCK-8 method and flow cytometry were used to detect cell proliferation and apoptosis in each group. Lactate dehydrogenase (LDH), superoxide dismutase (SOD), malonaldehyde (MDA), catalase (CAT) levels were detected. Western blotting was used to detect the expression of Bcl-2 associated X Protein (Bax) and B cell lymphoma/lewkmia-2 (Bcl-2). Target genes of miR-488 were predicted, and a luciferase reporter system was used to verify the targeting relationship between the two. Myocardial H9c2 cells were co-transfected with miR-488 inhibitor and Jag1 siRNA, and treated with hypoxia and reoxygenation, cell proliferation, apoptosis, LDH, SOD, MDA, CAT levels, and Bax, Bcl-2 protein expression were detected. RESULTS: The expression of miR-488 in the hypoxia-reoxygenated myocardial H9c2 cells was increased, along with reduced cell proliferation, increased apoptosis, increased Bax protein expression, decreased Bcl-2 protein expression, increased MDA, decreased CAT and SOD, and increased LDH level in the supernatant of cell culture. When myocardial H9c2 cells were transfected with miR-488 inhibitor and treated with hypoxia and reoxygenation, the expression of miR-488 was decreased, along with increased cell proliferation, decreased apoptosis, decreased Bax protein expression, increased Bcl-2 protein expression, decreased MDA, increased CAT and SOD, and decreased LDH level in the supernatant of cell culture. Down-regulation of miR-488 could target and down-regulate Jag1 expression. And Jag1 siRNA could reverse the effect of miR-488 inhibitor on the proliferation, apoptosis, LDH, SOD, MDA, CAT levels and the expression of Bax and Bcl-2 of hypoxic-reoxygenated myocardial H9c2 cells. CONCLUSION: Down-regulating miR-488 targeted Jag1 can attenuate hypoxia-reoxygenation induced myocardial H9c2 cell injury.

[Effect of miR-125a-5p targeting Scarb1 gene on hypoxia/reoxygenation injury of cardiomyocytes and its mechanism].

OBJECTIVE: To explore the effect and mechanism of miR-125a-5p targeted regulation of scavenger receptor B1 (Scarb1) gene on anoxia/reoxygenation injury of rat cardiomyocytes. METHODS: H9c2 rat cardiomyocytes were randomly divided into blank control group, hypoxia/reoxygenation group, transfection control group and mir-125a-5p transfection group. The expression of miR-125a-5p, cardiomyocyte viability, apoptosis rate, ATP content and the expression of Scarb1, Cyt C, Bax, Bcl-2 and NF-κB signaling pathway related proteins were determined. Target gene of miR-125a-5p was predicted with Targetscan software, and the targeting of miR-125a-5p on Scarb1 was verified by double luciferase reporter gene experiment. RESULTS: Compared with the blank control group, the expression of miR-125a-5p, Bax, Cyt C and the apoptotic rate of cardiomyocytes in the hypoxia/reoxygenation group were significantly increased (P<0.05), while the expression of Scarb1, Bcl-2 and the content of ATP were significantly decreased (P<0.05). Compared with the control group, the situation of mir-125a-5p transfection group was just the opposite. Double luciferase reporter gene experiment has confirmed Scarb1 to be the target of miR-125a-5p. Hypoxia/reoxygenation can promote the expression of NF-κB p65, C-myc and Cyclin D1 in cardiomyocytes, while down-regulating the expression of miR-125a-5p can inhibit the expression of such proteins. CONCLUSION: Hypoxia/reoxygenation can induce the expression of miR-125a-5p in rat cardiomyocytes. Inhibition of miR-125a-5p can protect cardiomyocytes from hypoxia/reoxygenation by up-regulating the expression of Scarb1. The mechanism may be related to the inhibition of activation of NF-κB signaling pathway.

One-step fabrication of polylactic acid (PLA) nanofibrous membranes with spider-web-like structure for high-efficiency PM0.3 capture.

High-efficiency air filters are in high demand to protect human health from the threat of ultrafine particulate matters (PM). However, most commercial air filters are less effective for PM0.3 capture and/or still suffer from undesirable pressure drops. They are also typically petroleum-based. Herein, a double-jet synchronous electrospinning technology was demonstrated to fabricate spider-web-like polylactic acid (PLA) nanofibrous membranes (SPNM) in one step. The properties of spinning solutions were regulated to construct favorable multi-scale nanofiber and bead structures that mimicked the structural units in spider-webs. The as-prepared SPNM exhibited excellent filtration efficiency (99.87 %) and high quality factor (0.321 Pa-1) against the PM0.3, while presenting an attractively low pressure drop (19 Pa). Additionally, the filtration performance of SPNM was almost completely preserved during 10-cycle tests and the 6-month long-term tests, showing excellent function stability and durability. Benefiting from its good hydrophobicity (WCA = 143.2°), SPNM also presented a satisfactory filtration efficiency (>99.37 %) with low pressure drop (18 Pa) at an environment with humidity at 90 % against PM0.3. Furthermore, the unique structure increased the mechanical strength of SPNM, facilitating the processability for practical applications. Overall, this work may shed light on a promising approach for developing biomass-based, highly efficient filtration materials with hierarchical structures.

Reciprocal relationship between plasma ghrelin level and arterial stiffness in hypertensive subjects.

Arterial stiffness, considered an independent predictor of cardiovascular morbidity and mortality, is closely associated with hypertension. Futhermore, the role of ghrelin in the development of hypertension has been widely recognized. The purpose of the present study was to explore the potential relationship between circulating ghrelin and arterial stiffness in hypertensive subjects. A total of 192 patients with primary hypertension and 107 normotensive (NT) control subjects were enrolled in the present cross-sectional study. Plasma ghrelin was determined by ELISA. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV) and the augmentation index (AIx). Both baPWV and AIx values were markedly higher in the hypertensive compared with NT group (P < 0.01). In contrast, plasma ghrelin concentrations were significantly lower in hypertensive patients compared with NT subjects (P < 0.01). Plasma ghrelin concentrations were negatively correlated with age (odds ratio (OR) -1.836; P < 0.001), smoking (OR -1.347; P = 0.042), baPWV (OR -1.762; P < 0.001) and AIx (OR -1.516; P = 0.005), but positively associated with fasting plasma glucose (OR 1.293; P = 0.047) and HbA1c (OR 1.413; P = 0.025). The inverse correlation between circulating ghrelin and the extent of arterial stiffness suggests that ghrelin is an independent determinant of arterial stiffness, even after adjustment for confounding cardiovascular risk factors, and it actively participates in the pathophysiology of arterial stiffness in hypertensive subjects.

[Effects of Ghrelin on hypertension and insulin resistance in fructose-fed rats].

OBJECTIVE: To explore the effects and mechanisms of Ghrelin on hypertension and insulin resistance in fructose-fed rats. METHODS: A total of 32 male Sprague-Dawley (SD) rats were randomized into control (A) and fructose-fed groups (B). Rats in group B were fed with 10% fructose solution for 4 weeks. Then the rats in group A were randomized into intraperitoneal saline (group GA1) or intraperitoneal 50 nmol/kg Ghrelin (group GA2) and those in group B into intraperitoneal saline (group GB1) or intraperitoneal 50 nmol/kg Ghrelin (group GB2) twice daily for 6 weeks. Caudal arterial pressure was measured weekly. Plasma blood glucose, insulin concentration and lipid profile were measured. And insulin resistance (IR) was calculated by the method of homeostasis model assessment (HOMA). Plasma level of 15-F2t-isoprostane was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Ghrelin caused a significant reduction of systolic pressure at Week 3 in group GB2 versus group GB1 (P < 0.05). Maximal effect appeared at Week 5 ((127 ± 5) vs (120 ± 6) mm Hg, P < 0.05, 1 mm Hg = 0.133 kPa), but blood pressure failed to reach normal value. Ghrelin also decreased plasma insulin concentration and HOMA-IR ((9.6 ± 2.6) vs (13.1 ± 3.6) µU/ml, P < 0.05;1.92 ± 0.12 vs 2.78 ± 0.14, P < 0.01). Plasma level of 15-F2t-isoprostane was lower in group GB2 than that in group GB1 ((75 ± 11) vs (102 ± 14) pg/ml, P < 0.01). CONCLUSION: Ghrelin may lower blood pressure, ameliorate insulin resistance and improve insulin sensitivity through inhibiting oxidative stress in fructose-induced rats.

Evaluation of Mask Performances in Filtration and Comfort in Fabric Combinations.

A systemic study on improving particulate pollutant filtration efficiency through the combination of conventional fabrics is presented with the objective of finding comfortable, yet effective airway mask materials and products. Fabrics, nonwovens, and their combinations made of cotton, silk, wool, and synthetic fibers are examined on their filtration efficiency for aerosol particles with diameters ranging from 0.225 µm to 3.750 µm under industry-standard testing conditions. It is found that composite fabrics can improve filtration efficiency more than just layers of the same fabric, and the filtration quality factor of some of the fabric combinations can exceed that of the standard melt-blown materials. In addition, fabric friction and charging between the combined layers also improve filtration efficiency substantially. With a broader understanding of the fabric characteristics, we may design mask products with reduced facial skin discomfort, better aesthetics, as well as the ability to alleviate the environmental impact of discarded protective masks in the extended period of controlling the transmission of pollutants and viruses, such as during the COVID-19 pandemic.

Enhanced stereocomplex crystalline polylactic acids in melt processed enantiomeric bicomponent fiber configurations.

The formation of stereocomplex crystalline domains in the bicomponent fiber melt spinning of enantiomeric polylactic acids (PLAs) is systematically explored and enhanced. Here we report a polycrystalline morphology where distinctly different crystalline regions are formed and aligned along the longitudinal direction of the fiber. This approach employs side-by-side and sheath-core bicomponent melt spinning configurations where the two components are the enantiomeric pairs of poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA). We demonstrate the formation of the PLA stereocomplexes at the junction interphase through the melt spinning process which subsequently crystallize into a round fibers with stereocomplex and homogeneous crystal lamella morphologies. The fiber morphologies and crystallinities of the melt processed fiber are substantially different from the solution based bicomponent spinning system reported in the prior literature. Furthermore, the different molecular weight in the PLLA/PDLA pairing are found to be crucial to the structural development and properties of the PLA polycrystalline materials. The solid-state annealing does not change the crystal distribution of the crystalline domains and stereocomplex crystalline state, it just enhances the homo-crystallinity in the peripheral of the bicomponent fibers.

Clinical characteristics and survival analysis of class I pulmonary arterial hypertension.

PURPOSE: To analyze the clinical data and prognosis of patients with World Health Organization (WHO) functional class I pulmonary arterial hypertension (PAH). METHODS: This research retrospectively analyzed the clinical data (baseline, laboratory as well as echocardiography and right heart catheterization data) of 63 class I PAH patients diagnosed and treated in the Department of Cardiology, First Affiliated Hospital of Zhengzhou University, between January 2021 and June 2022. The mean follow-up time was 10.7±6.5 months. The treatment and prognosis of the patients were analyzed. RESULTS: Among the class I PAH patients, the average age at diagnosis was 39.7±12.7 years, with females accounting for 92.1%; 44.4% of patients were at grade III or IV; 55.6% were at medium-high risk. In the subgroup analysis, there were more cases with grade III/IV cardiac function (P=0.03) and high risk in idiopathic PAH (IPAH) group than those in congenital heart disease-associated (CHD-PAH) and connective tissue disease-associated PAH (CTD-PAH) groups (P=0.04). CHD-PAH patients tended to present with higher pulmonary systolic blood pressure, mean pulmonary artery pressure and pulmonary vascular resistance than CTD-PAH patients (P<0.01), while IPAH patients had worse right ventricular end-systolic and end-diastolic volumes (P<0.05). The three subgroups showed no obvious differences in echocardiographic indexes (right atrial size, right ventricular size and pulmonary artery systolic pressure) and related laboratory indexes (blood routines and hepatorenal function). In terms of the targeted drug therapy for PAH, the proportion of dual-drug combination therapy was the highest (48.1%), followed by monotherapy (35%) and triple combination therapy (15.9%). Nearly half (48.7%) of CTD-PAH cases were first diagnosed in the Rheumatology and Immunology Department, and all of them were given targeted drug therapy for PAH. After a mean follow-up of 10.7±6.5 months, a total of 8 endpoint events occurred, including 3 deaths due to CTD-PAH complicated with serious complications of other organs. The 1-year survival rate for all the included PAH patients was 95.2%. CONCLUSIONS: In the era of targeted therapy, class I PAH patients in China have a high early survival rate, a high proportion of combined therapy and strong multidisciplinary attention.

Retrospective on global pulmonary hypertension clinical trials: 1999-2021.

Background: Data are quite sparse on the comprehensive analyses of pulmonary hypertension (PH) clinical trials worldwide. Methods: Information including participating countries (developed or developing), intervention type, trial size, PH categories, sponsorship, study phase, design strategies, and participants' demographic characteristics was extracted from PH trials registered on ClinicalTrials.gov from 1999 to 2021. Results: A total of 203 eligible clinical PH trials were screened, involving 23,402 participants, 67.8% of whom were females. Major clinical trials were designed to test drug interventions (95.6%), sponsored solely by industries in 59.5%, and targeting Group 1 PH patients in 76.3%. A large number of countries participated in PH clinical trials; however, most clinical trials were conducted in developed countries (84.2%). Developing countries were involved in clinical trials with larger sample sizes (P<0.01). Additionally, the differences between developed and developing countries centered on interventions, sponsors, PH groups, and design strategies. Furthermore, developing countries participated in multinational clinical trials with good quality, homogeneity, reliability, and data authenticity. All pediatric participants were diagnosed with Group 1 PH and were only involved in drug intervention trials. Children participated in far fewer clinical trials than adults (P<0.01), and most were enrolled in PH clinical trials in developed countries. Among the entire clinical trial population, younger patients with Group 1 PH had a much higher participation to prevalence ratio (PPR). There was no difference in women's PPRs between developed and developing countries. However, developing countries had higher PPRs for PH Groups I and IV (1.28 vs. 1.22, P<0.01), while developed countries had a lower PPR for Group III (P=0.02). Conclusions: PH is attracting increasing global attention, which is not at the same level of progress in developed and developing countries. Women and children with this disease have unique characteristics and require more attention.

[Effects of domestic rosuvastatin on coronary plaque in patients with mild-to-moderate coronary artery stenosis as evaluated by virtual histology-intravascular ultrasound].

OBJECTIVE: To evaluate the effects of domestic rosuvastatin tablets on coronary plaque in the patients with mild-to-moderate coronary artery stenosis through virtual histology-intravascular ultrasound (VH-IVUS). METHODS: Eighty-three patients with mild-to-moderate coronary artery stenosis of acute coronary syndrome (ACS) were enrolled and randomized into test group (domestic rosuvastatin, 10 mg/day, n = 42) or control group (CRESTOR, 10 mg/day, n = 41). The serum lipid levels, diameter stenosis (DS) on quantitative coronary angiography (QCA), MLA (minimal lumen area), plaque burden and component of target lesion on VH-IVUS were evaluated at baseline and at 6-month follow-up. RESULTS: After 6 months, the levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) significantly decreased while the high density lipoprotein cholesterol (HDL-C) level significantly increased in two groups(P < 0.05). VH-IVUS analysis showed that the proportion of necrotic core significantly decreased (domestic rosuvastatin: 14.8% ± 7.0% vs 22.6% ± 7.5%, P < 0.05, crestor: 14.9% ± 7.1% vs 23.1% ± 7.7%, P < 0.05) and the proportion of fibrous tissue significantly increased (domestic rosuvastatin: 51.5% ± 9.9% vs 44.5% ± 9.7%, P < 0.05, crestor: 51.4% ± 10.1% vs 44.3% ± 9.8%, P < 0.05) in two groups. There were no significant changes in DS, plaque burden, MLA or the proportion of dense calcium and fibro-fatty tissue of target lesion in two groups (P > 0.05). And no significant differences existed in serum lipid levels, DS, MLA, plaque burden and component between two group(P > 0.05). CONCLUSION: The 6-month treatment of rosuvastatin may stabilize the atherosclerosis plaque and prevent its progression in patients with mild-to-moderate coronary artery stenosis.

A Review on Nanocellulose and Superhydrophobic Features for Advanced Water Treatment.

Globally, developing countries require access to safe drinking water to support human health and facilitate long-term sustainable development, in which waste management and control are critical tasks. As the most plentiful, renewable biopolymer on earth, cellulose has significant utility in the delivery of potable water for human consumption. Herein, recent developments in the application of nanoscale cellulose and cellulose derivatives for water treatment are reviewed, with reference to the properties and structure of the material. The potential application of nanocellulose as a primary component for water treatment is linked to its high aspect ratio, high surface area, and the high number of hydroxyl groups available for molecular interaction with heavy metals, dyes, oil-water separation, and other chemical impurities. The ability of superhydrophobic nanocellulose-based textiles as functional fabrics is particularly acknowledged as designed structures for advanced water treatment systems. This review covers the adsorption of heavy metals and chemical impurities like dyes, oil-water separation, as well as nanocellulose and nanostructured derivative membranes, and superhydrophobic coatings, suitable for adsorbing chemical and biological pollutants, including microorganisms.

Leucine-rich repeat kinase-2 deficiency protected against cardiac remodelling in mice via regulating autophagy formation and degradation.

Introduction: Leucine-rich repetitive kinase-2 (LRRK2) is a Parkinson's disease-related gene that also participates in many inflammatory diseases. However, the functional role of LRRK2 in cardiovascular disease is not clear. Objective: In this study, we aimed to elucidate the role of LRRK2 in cardiac remodelling under pressure overload. Methods: Aortic banding surgery was performed to induce cardiac remodelling in a LRRK2 knockout mouse model. A cardiomyocyte remodelling model was established by phenylephrine (PE) stimulation in neonatal rat cardiomyocytes. Results: LRRK2 was upregulated in remodelled mouse hearts and cardiomyocytes. Cardiac hypertrophy, fibrosis and dysfunction were ameliorated in LRRK2 knockout mice. LRRK2 silencing protected against the PE-induced cardiomyocyte hypertrophic response, while LRRK2 over-expression worsened the PE-induced hypertrophic response in cardiomyocytes. Decreased autophagy was observed in remodelled cardiomyocytes, whereas LRRK2 silencing increased autophagy levels and LRRK2 overexpression reduced autophagy levels. The autophagy inhibitors 3-MA, bafilomycin and chloroquine reversed the protective effects of LRRK2 deficiency. The autophagy activator rapamycin reversed the deleterious effects of LRRK2 overexpression. We found that LRRK2 inhibited Bcl-2 phosphorylation, thus decreasing the phosphorylation of Beclin1. The protective effects of LRRK2 knockout were partly counteracted by Beclin1(+/-) in vivo and Beclin1 silencing in vitro. We also observed an interaction between LRRK2 and Rab7, an autolysosome degradation-associated protein, which caused Rab7 downregulation. Rab7 knockdown almost completely reversed LRRK2 silencing-induced protection of cardiomyocytes. Conclusion: LRRK2 deficiency protected against cardiac remodelling under pressure overload by increasing Bcl-2/Beclin1 and Rab7-regulated autophagy levels in the heart.

Relationship between plasma ghrelin levels and insulin resistance and blood pressure in octogenarians.

The association between fasting plasma ghrelin levels and insulin resistance and blood pressure (BP) in octogenarians was investigated in this study. A total of 487 unrelated octogenarians (including 203 men and 284 women) were enrolled in this cross-sectional study at the Healthy Care Center of Shanghai East Hospital, Tongji University, China, from October 2008 to April 2009. Plasma ghrelin was determined by using the enzyme linked immunosorbent assay (ELISA). Insulin sensitivity was assessed using the homeostasis model of assessment-insulin resistance (HOMA-IR). The age of the participants ranged from 80 to 89 years (mean=83.9+/-4.8 years) with a body mass index (BMI) of 25.3+/-4.9 kg/m2. Plasma ghrelin levels were 20.94+/-5.34 microg/L, being 20.89+/-5.53 microg/L in men and 21.38+/-3.73 microg/L in women respectively. Plasma ghrelin was not associated with systolic (P=0.981) or diastolic (P=0.724) BP, waist circumference (P=0.278), fasting insulin (P=0.246), fasting blood glucose (FBG) (P=0.693) and HOMA-IR (P=0.232). In the control cohort, no significant differences in plasma ghrelin were found between genders (P=0.489), and among subjects with hypertension (BP>140/90 mmHg) (P=0.284) and type 2 diabetes (P=0.776). In conclusion, fasting plasma ghrelin levels are not directly correlated with insulin resistance and BP among octogenarians.

CTRP5-Overexpression Attenuated Ischemia-Reperfusion Associated Heart Injuries and Improved Infarction Induced Heart Failure.

Aims: C1q/tumor necrosis factor (TNF)-related protein 5 (CTRP5) belongs to the C1q/TNF-α related protein family and regulates glucose, lipid metabolism, and inflammation production. However, the roles of CTRP5 in ischemia/reperfusion (I/R) associated with cardiac injuries and heart failure (HF) needs to be elaborated. This study aimed to investigate the roles of CTRP5 in I/R associated cardiac injuries and heart failure. Materials and Methods: Adeno-associated virus serum type 9 （AAV9）vectors were established for CTRP5 overexpression in a mouse heart (AAV9-CTRP5 mouse). AAV9-CTRP5, AMPKα2 global knock out （AMPKα2-/-）and AAV9-CTRP5+ AMPKα2-/- mice were used to establish cardiac I/R or infarction associated HF models to investigate the roles and mechanisms of CTRP5 in vivo. Isolated neonatal rat cardiomyocytes (NRCMS) transfected with or without CTRP5 adenovirus were used to establish a hypoxia/reoxygenation (H/O) model to study the roles and mechanisms of CTRP5 in vitro. Key Findings: CTRP5 was up-regulated after MI but was quickly down-regulated. CTRP5 overexpression significantly decreased I/R induced IA/AAR and cardiomyocyte apoptosis, and attenuated infarction area, and improved cardiac functions. Mechanistically, CTRP5 overexpression markedly increased AMPKα2 and ACC phosphorylation and PGC1-α expression but inhibited mTORC1 phosphorylation. In in vitro experiments, CTRP5 overexpression could also enhance AMPKα2 and ACC phosphorylation and protect against H/O induced cardiomyocytes apoptosis. Finally, we showed that CTPR5 overexpression could not protect against I/R associated cardiac injuries and HF in AMPKα2-/- mice. Significance: CTRP5 overexpression protected against I/R induced mouse cardiac injuries and attenuated myocardial infarction induced cardiac dysfunction by activating the AMPKαsignaling pathway.

Follistatin-Like 1 Protects against Doxorubicin-Induced Cardiomyopathy through Upregulation of Nrf2.

Doxorubicin- (DOX-) induced cardiomyocyte loss results in irreversible heart failure, which limits the clinical applications of DOX. Currently, there are no drugs that can effectively treat DOX-related cardiotoxicity. Follistatin-like 1 (FSTL1) has been reported to be a transforming growth factor-beta-inducible gene, and FSTL1 supplementation attenuated ischemic injury and cardiac apoptotic loss in mice. However, the effect of FSTL1 on DOX-induced cardiomyopathy has not been elucidated. We aimed to explore whether FSTL1 could prevent DOX-related cardiotoxicity in mice. Mice were intraperitoneally injected with a single dose of DOX to induce acute cardiotoxicity. We used an adeno-associated virus system to overexpress FSTL1 in the heart. DOX administration decreased FSTL1 mRNA and protein expression in the heart and in cells. FSTL1 prevented DOX-related cardiac injury and inhibited cardiac oxidative stress and apoptosis, thereby improving cardiac function in mice. FSTL1 also improved cardiomyocyte contractile functions in vitro. FSTL1 upregulated expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in DOX-treated hearts. FSTL1 was not capable of protecting against these toxic effects in Nrf2-deficient mice. In conclusion, FSTL1 protected against DOX-induced cardiotoxicity via upregulation of Nrf2 expression.

Hyperoside Suppresses Lipopolysaccharide-induced Inflammation and Apoptosis in Human Umbilical Vein Endothelial Cells.

Finding the novel drug from the effective components of traditional Chinese herbal medicine is a hotspot of the modern pharmacological research. Hyperoside (HYP) belongs to flavonoid glycosides, and it has various properties, such as anti-inflammation, anti-spasm, anti-diuretic, antitussive, lowering blood pressure, and lowering cholesterol effects as well as protective effects for the cardiac and cerebral blood vessels. The purpose of this study was to investigate the effects of HYP on inflammatory and apoptotic responses in vascular endothelial cells stimulated by lipopolysaccharide (LPS) and further to identify the possible mechanisms underlying these effects. In our study, human umbilical vein endothelial cells (HUVECs) were stimulated with 1 µg/mL LPS in the presence or absence of HYP (10, 20 and 50 µmol/L). Our results indicated that HYP alone exerted no cytotoxicity on HUVECs, while it had an up-regulatory effect on the viability of HUVECs induced by LPS in a dose-dependent manner; increased mRNA expression of IL-1ß, IL-6, TNFα and iNOS induced by LPS was attenuated after treatment with HYP both in a dose-and time-dependent manner; LPS-induced HUVECs apoptosis and cleaved-caspase 8, 9, 3 were all significantly reduced by HYP. Furthermore, the possible pathway involved in apoptosis and inflammation by HYP was detected, and the results showed that when treated with HYP, LPS-induced mitochondrial membrane instability was significantly inhibited through up-regulation of Bcl-2 and down-regulation of Bax. Furthermore, the expression of TLR4 and the phosphorylation of IκBα and p65 in LPS-treated cells were blocked by HYP. Our results suggested that HYP treatment prevented HUVECs from LPSinduced inflammation and apoptosis responses, which might be mediated by inhibiting TLR4/NFκB pathway.

Concentration­dependent effects of paeoniflorin on proliferation and apoptosis of vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) are an important component of arterial walls, and their dysfunction may serve an important role in the development of cardiovascular diseases, including atherosclerosis and restenosis. Paeoniflorin (PF) is a principal component of the commonly used traditional Chinese medicine, peonies. To the best of our knowledge, the effects of PF on apoptosis and proliferation of VSMCs and its underlying molecular mechanisms have not been widely reported. Therefore, the present study was designed to investigated this phenomenon. VSMCs were treated with different concentrations of PF (25, 50 and 100 µg/ml) for 12, 24 or 48 h. The data demonstrated that PF treatment not only significantly decreased cell viability and DNA synthesis but also blocked G0/G1 cell cycle progression. This effect was associated with a decreased expression of cyclin D1, cyclin E, cyclin­dependent kinase (CDK)4 and CDK2 as well as an upregulation of p21. Notably, a significant concentration­dependent decrease in the phosphorylation of p65 and nuclear factor of κ light polypeptide gene enhancer in B­cells inhibitor­α (IκBα) was observed. In addition, it was demonstrated that PF promoted the apoptosis of VSMCs, which was associated with the increased expression of caspases. In conclusion, PF inhibited the proliferation of VSMCs by downregulating proteins associated with the nuclear factor­κB signaling pathway. Furthermore, it promoted the apoptosis of VSMCs by upregulating the expression of caspases. These results may be useful in improving the understanding of the molecular mechanisms underlying the apoptotic and anti­proliferative effects of PF on VSMCs, and facilitate the development of novel treatments for cardiovascular diseases.

Schwann cells and fibronectin treating lesioned spinal cord of adult rats.

OBJECTIVE: To determine whether Schwann cells (SCs) and fibronectin (FN) support the growth of damaged axons and their conductive function. METHODS: Thirty adult Sprague-Dawley (SD) rats were randomized into 3 groups (n=10), and the following grafts: both SCs and FN, FN, and basal medium were implanted respectively into the lumbar of spinal cords hemisected at vertebra T(12). RESULTS: At 6 weeks postoperation, the latencies of spinal cord evoked potential (SCEP) P(1) wave in the three groups were 1.57 ms, 1.84 ms, and 2.03 ms, respectively. The differences between SCs/FN group and the other two groups were statistically significant. The number of regenerated axons in SCs/FN group was significantly greater than that in FN group. The number of survival neurons in L(4) and L(5) left dorsal root ganglia (DRG) in SCs/FN group was significantly greater than that in the rest two groups respectively. The latencies of P(1) wave were significantly correlated with axon counts in both SCs/FN and FN groups. CONCLUSIONS: SCs/FN grafted to the hemisected lumbar of spinal cords can produce robust axon regeneration and promote partial repair of their conduction. Surface recording of SCEP technique has been proved to be a reliable and less-traumatic method for assessment of recovery of afferent conduction in hemisected spinal cord.

Circulating obestatin levels correlate with fasting insulin and HOMA-IR but not with hypertension in elderly men.

Obestatin, encoded by the same gene as ghrelin, was first described as a physiological opponent of ghrelin. The association between circulating obestatin levels and blood pressure remains unclear. Furthermore, adequate information is non-existent regarding the older male population with hypertension. For this purpose, we enrolled 185 unrelated hypertensive male patients aged ≥ 80 years (range 80-102 years). One hundred seventy nine age-matched healthy subjects served as controls. Plasma levels of obestatin and insulin were measured using commercial ELISA and RIA. HOMA-IR was calculated using standard method. We found that plasma obestatin levels correlated significantly with insulin levels (P = 0.034) and homeostasis model assessment index for insulin resistance (HOMA-IR: P = 0.028). However, plasma obestatin differed non-significantly between hypertensive (5.06 ± 0.68 ng/mL) and non-hypertensive (4.72 ± 0.82 ng/mL) individuals. Plasma obestatin levels were not associated with systolic (P = 0.818) or diastolic (P = 0.564) blood pressure, waist-to-hip ratio (WHR: P = 0.725), uric acid (P = 0.603), total cholesterol (TC: P = 0.589), low-density lipoprotein cholesterol (LDL-C: P = 0.057); high-density lipoprotein cholesterol (HDL-C: P = 0.432), triglyceride (TG: P = 0.418), and fasting blood glucose (FBG: P = 0.101). We, therefore, concluded that fasting circulating obestatin levels did not directly correlate with blood pressure in men aged ≥ 80 years.