Alginate oligosaccharide alleviates vascular aging by upregulating glutathione peroxidase 7.

Alginate oligosaccharide (AOS) may delay aging by decreasing oxidative stress, but the effects on vascular aging remain unclear. Here, we evaluate the effect of AOS on vascular aging and investigate the underlying mechanisms. Twenty-month-old rats acted as the natural aging model in vivo. Senescence of human aortic vascular smooth muscle cells (HA-VSMCs) was induced in vitro using angiotensin II (AngII). The aging rats and senescent cells were treated with AOS, followed by assessment of aging makers, oxidative stress, and aging-induced vascular remodeling. AOS treatment alleviated vascular aging and HA-VSMC senescence and decreased the levels of oxidative stress and vascular remodeling-associated indicators. AOS upregulated the expression of glutathione peroxidase 7 (GPX7) in aging rats and GPX7 depletion disrupted the geroprotective effect of AOS. AOS increased the nuclear translocation of nuclear factor erythroid-2-related factor (Nrf2) protein, which interacts with GPX7 protein to induce its expression. In conclusion, AOS alleviates vascular aging and HA-VSMC senescence and reduces aging-related vascular remodeling via the GPX7 antioxidant pathway, which may provide new avenues for treating aging-associated diseases.

Alginate oligosaccharide alleviates aging-related intestinal mucosal barrier dysfunction by blocking FGF1-mediated TLR4/NF-κB p65 pathway.

BACKGROUND: Alginate oligosaccharide (AOS) has been reported to exert a crucial role in maintaining the intestinal mucosal barrier (IMB) function. The current study aimed at ascertaining the protective effects of AOS on aging-induced IMB dysfunction and to elucidate the underlying molecular mechanisms. METHODS: An aging mouse model and a senescent NCM460 cell model were established using d-galactose. AOS was administered to aging mice and senescent cells, and IMB permeability, inflammatory response and tight junction proteins were assessed. In silico analysis was conducted to identify factors regulated by AOS. Using gain- and loss-of-function approaches, we evaluated the roles of FGF1, TLR4 and NF-κB p65 in the aging-induced IMB dysfunction and NCM460 cell senescence. RESULTS: AOS protected the IMB function of aging mice and NCM460 cells by reducing permeability and increasing tight junction proteins. In addition, AOS up-regulated FGF1, which blocked the TLR4/NF-κB p65 pathway, and identified as the mechanism responsible for the protective effect of AOS. CONCLUSION: AOS blocks the TLR4/NF-κB p65 pathway via inducing FGF1, ultimately reducing the risk of IMB dysfunction in aging mice. This study highlights the potential of AOS as a protective agent against aging-induced IMB disorder and provides insight into the underlying molecular mechanisms.

Chinese expert consensus on prevention and control interventions for older adults with physical functional impairment (2022).

Older adults are at high risk for functional impairment, which is closely related to sarcopenia, falls, and frailty. This seriously affects their quality of life and health, and places a heavy burden on society and families. Although domestic and foreign sports recommendations and prevention and control guidelines/expert consensus have been issued for healthy older adults and functional impairment-related diseases, there is no guidance on prevention and control interventions for older adults with physical functional impairment. In China, there is insufficient understanding of the importance of prevention and control interventions for functional impairment in older adults, and there are many drawbacks, such as unstandardized diagnosis and treatment, and relatively simple intervention methods. Therefore, the consensus expert group formulated a consensus based on domestic and foreign guidelines related to functional impairment in older adults to provide guidance for Chinese medical professionals working in the field of geriatrics.

Astragalus polysaccharides alleviates cardiac hypertrophy in diabetic cardiomyopathy via inhibiting the BMP10-mediated signaling pathway.

BACKGROUND: Cardiac hypertrophy can lead to cardiac dysfunction and is closely associated with mortality in diabetic cardiomyopathy (DCM). Astragalus polysaccharides (APS) is the main component extracted from Astragalus membranaceus (Fisch.) Bunge (AM), which exhibits anti-hypertrophic effects on cardiomyocytes in various diseases. However, whether APS exerts anti-hypertrophic effects in DCM remains unclear. PURPOSE: To investigate whether APS can attenuate cardiac hypertrophy in DCM and exert anti-hypertrophic effects by inhibiting the bone morphogenetic protein 10 (BMP10) pathway. METHODS: The anti-hypertrophic effects of APS were studied in high-glucose (HG)-stimulated H9c2 cardiomyocytes and streptozotocin (STZ)-induced DCM rats. BMP10 siRNA was used to inhibit BMP10 expression in H9c2 cardiomyocytes. Cardiac function was assessed by echocardiography. Cardiac hypertrophy was evaluated using heart weight/body weight (HW/BW), RT-PCR, hematoxylin-eosin (HE), and rhodamine phalloidin staining. Changes in hypertrophic components, including BMP10 and downstream factors, were measured using western blotting. RESULTS: In vitro, HG treatment increased the relative cell surface area of H9c2 cardiomyocytes, whereas BMP10 siRNA transfection or APS treatment alleviated the increase induced by HG. APS treatment improved the general condition, increased cardiac function, and decreased the HW/BW ratio, ANP mRNA level, and cardiomyocyte cross-sectional area of DCM rats in vivo. Molecular experiments demonstrated that APS downregulated the levels of the pro-hypertrophic protein BMP10 and its downstream proteins ALK3, BMPRII, and p-Smad1/5/8 without affecting the level of total Smad1/5/8. CONCLUSIONS: Our study demonstrates that APS can alleviate cardiac hypertrophy and protect against DCM by inhibiting activation of the BMP10 pathway. APS is a promising candidate for DCM treatment.

Diet quality of primary and secondary school students in Yunnan Province / 中国学校卫生

Objective@#To evaluate diet quality and related problems among children and adolescents in Yunnan Province, in order to provide a theoretical basis for the formulation of targeted dietary interventions for children and adolescents in this region.@*Methods@#Using a stratified random sampling method, 1 078 primary and secondary school students from six prefecture level cities in Yunnan Province were selected from August to November 2022. Dietary quality was evaluated by applying the China Children s Dietary Index (CCDI-2016) on the basis of a 3 d 24 h dietary survey.@*Results@#The total dietary index score of children and adolescents in Yunnan Province was 62.63(54.57,71.19). The overall recommended intakes were largely achieved by consumption of cereals, eggs and sugary drinks, with dietary index scores of 9.91(8.24,10.00), 5.58(0,8.58) and 9.20(7.38,10.00), respectively; there were inadequate intakes of vegetables, legumes, water, vitamin A and dietary fiber, with scores of 5.63(4.09,7.59), 3.48 (0,9.70), 4.23(2.67,5.50), 2.33(1.56,3.53), 3.19(1.63,5.67), respectively; intake of fruits, dairy and aquatic products were severely deficient, with scores of 0(0,1.74), 0(0,2.37), 0(0,9.85), respectively; excessive intake of meat was found, with a dietary index score of 0(0,2.46). The stratified analysis showed that children and adolescents aged 11-13 years had the highest total dietary scores[65.35(54.29,72.03)], followed by those aged 7-10 years[63.46(56.19,72.63)], while the 14-17 year old age group had the lowest scores[59.07(51.15,68.30), H=32.23, P <0.01]. Girls had higher total dietary scores than that of boys[64.20(56.12,72.56), 59.32(52.60,69.72), Z=-5.16, P <0.01], while urban children and adolescents had higher total dietary scores than rural children and adolescents[65.30(54.84,73.62), 62.17(54.31,70.70), Z=-2.11, P <0.05]. Furthermore, higher total dietary index scores were observed among children and adolescents whose parents had a higher educational level( H=27.68, 22.58, P <0.01). The comparison of ethnic groups revealed that the Wa children and adolescents had the highest total dietary index scores, while the Hani children had the lowest( H=27.51, P <0.01).@*Conclusion@#The overall dietary quality of children and adolescents in Yunnan Province is not high, the imbalance of dietary nutrition is prominent, and the dietary structure needs to be adjusted and optimized. Intervention programs should focus on the problem of insufficient intake of fruits and vegetables, milk and legumes, aquatic products and excessive intake of poultry meat among children and adolescents.

Chinese expert consensus on prevention and intervention for the elderly with malnutrition (2022).

Malnutrition is a state of altered body composition and body cell mass due to inadequate intake or utilization of energy or nutrients, leading to physical and mental dysfunction and impaired clinical outcomes. As one of the most common geriatric syndromes, malnutrition in the elderly is a significant risk factor for poor clinical outcomes, causing a massive burden on medical resources and society. The risk factors for malnutrition in the elderly are diverse and include demographics, chronic diseases, and psychosocial factors. Presently, recommendations for the prevention and intervention of malnutrition in the elderly are not clear or consistent in China. This consensus is based on the latest global evidence and multiregional clinical experience in China, which aims to standardize the prevention and intervention of malnutrition in the elderly in China and improve the efficacy of clinical practice and the prognosis of elderly patients.

Acidic oligosaccharide sugar chain combined with hyperbaric oxygen delays D-galactose-induced brain senescence in mice via attenuating oxidative stress and neuroinflammation.

Aging is fundamental to neurodegeneration and dementia. Preventing oxidative stress and neuroinflammation are potential methods of delaying the onset of aging-associated neurodegenerative diseases. The acidic oligosaccharide sugar chain (AOSC) and hyperbaric oxygen (HBO) can increase the expression of antioxidants and have a neuroprotective function. In this study, we investigate the ability of AOSC, HBO, and AOSC + HBO to prevent D-gal-induced brain senescence. The Morris water maze and Y-maze test results showed that all three therapies significantly attenuated D-gal-induced memory disorders. A potential mechanism of this action was decreasing elevated levels of oxidative stress and neuroinflammation. The western blot and morphological results showed that all three therapies decreased D-gal-induced neuroinflammation and downregulated inflammatory mediators including the nuclear factor κ-light-chain-enhancer of activated B cells, cyclooxygenase-2, interleukin-1ß, and tumor necrosis factor alpha. Taken together, our results indicated that AOSC, HBO, and AOSC + HBO therapies attenuated D-gal-induced brain aging in mice by repressing RAGE/NF-KB-induced inflammation, the activation of astrocytes and microglia, and a decrease in neuronal degeneration. These could be useful therapies for treating age-related neurodegenerative diseases such as Alzheimer's disease. Furthermore, HBO combined with AOSC had a better effect than HBO or AOSC alone.

Alginate oligosaccharide alleviates senile osteoporosis via the RANKL-RANK pathway in D-galactose-induced C57BL/6J mice.

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and bone quality and increased bone porosity, which increase the risk of bone fracture. Inflammation, one of the important mechanisms related to aging, is associated with osteoporosis. Treatment with anti-inflammatory agents is effective for alleviating senile osteoporosis. Alginate oligosaccharide (AOS) can prevent and treat diseases related to inflammation, oxidative stress, and immunity. This study evaluates the effect of AOS on osteoporosis and investigates the underlying mechanism. Osteoporosis model was induced by D-galactose (D-gal) (200 mg kg-1  day-1 ) for eight weeks. Three groups were administered via AOS (50, 100, and 150 mg kg-1  day-1 ) for four weeks, while a control group received sterile water (5 ml kg-1  day-1 ) for 8 weeks. The results showed that AOS improved bone density and bone microstructure in D-gal-induced osteoporosis mice. AOS inhibited osteoclast proliferation, probably through the suppression of receptor activator of nuclear factor-kappa B ligand (RANKL)-associated nuclear factor kappa B (NF-κB) and c-Fos signaling pathway. AOS also increased osteoprotegerin (OPG) expression and competitively inhibited the binding between RANK and RANKL in senile osteoporosis. Further, AOS decreased the secretion of serum osteocalcin and reduced bone conversion. Together, these results demonstrate the anti-osteoporosis activity of AOS in mice with osteoporosis.

Bromodomain-containing protein 7 contributes to myocardial infarction-induced myocardial injury through activating Wnt/ß-catenin signaling.

BACKGROUND: Myocardial infarction (MI) is one of the most common cardiovascular diseases, inducing severe myocardial injury and leading to high mortality. Bromodomain-containing protein 7 (BRD7), a member of bromodomain-containing protein family, is involved in multiple cellular processes, such as cell cycle, transcriptional regulation, and chromatin remodeling, but the functions of BRD7 in regulating MI-associated myocardial injury are still obscure. In this work, we investigated the effect of BRD7 on MI-induced myocardial injury in vitro and in vivo. METHODS: The MI model was established by ligating the left anterior descending coronary artery (LAD) of rats which were then injected with BRD7 short hairpin RNA (shRNA). The rat H9C2 cardiomyocytes were treated with hypoxia and injected with BRD7 shRNA. The expression of BRD7 in MI rat model, and hypoxia-treated H9C2 cells was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemical staining. The effect of BRD7 was analyzed using western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, echocardiography, and flow cytometry analysis. The expressions of Wnt/ß-catenin signaling relative proteins were determined by western blot. RESULTS: Significantly, BRD7 was highly expressed in MI patients, MI rat models, and hypoxia treated rat H9C2 cardiomyocytes. Echocardiography analysis demonstrated that the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were repressed in the MI rats relative to sham group rats, while the silencing of BRD7 rescued the dysfunction in the model. We also found that BRD7 silencing reduced cardiomyocyte apoptosis in both MI rats and H9C2 cells under the treatment of hypoxia. BRD7 silencing inhibited the activation of Wnt/ß-catenin signaling in H9C2 cells under the treatment of hypoxia. Moreover, Wnt agonist BML294 reversed the anti-apoptosis effect of BRD7 silencing in hypoxia-induced H9C2 cells. CONCLUSIONS: Collectively, we concluded that BRD7 contributed to MI-induced myocardial injury through activating Wnt/ß-catenin signaling. Targeting BRD7 may become a promising therapeutic strategy for the treatment of MI-induced myocardial injury.

The mechanisms of vascular aging.

Vascular senescence is one of the hotspots in current research. With global average life expectancy increasing, delaying or reducing aging and age-related diseases has become a pressing issue for improving quality of life. Vascular senescence is an independent risk factor for age-related cardiovascular diseases (CVD) and results in the deterioration of CVD. Nevertheless, the underlying mechanisms of the vascular senescence have not been expressly illustrated. In this review, we attempt to summarize the recent literature in the field and discuss the major mechanisms involved in vascular senescence. We also underline key molecular aspects of aging-associated vascular dysfunction in the attempt to highlight potential innovative therapeutic targets to delay the onset of age-related diseases.

Alginate oligosaccharide alleviates D-galactose-induced cardiac ageing via regulating myocardial mitochondria function and integrity in mice.

Ageing is a crucial risk factor for the development of age-related cardiovascular diseases. Therefore, the molecular mechanisms of ageing and novel anti-ageing interventions need to be deeply studied. Alginate oligosaccharide (AOS) possesses high pharmacological activities and beneficial effects. Our study was undertaken to investigate whether AOS could be used as an anti-ageing drug to alleviate cardiac ageing. D-galactose (D-gal)-induced C57BL/6J ageing mice were established by subcutaneous injection of D-gal (200 mg·kg-1 ·d-1 ) for 8 weeks. AOS (50, 100 and 150 mg·kg-1 ·d-1 ) were administrated intragastrically for the last 4 weeks. As a result, AOS prevented cardiac dysfunction in D-gal-induced ageing mice, including partially preserved ejection fraction (EF%) and fractional shortening (FS%). AOS inhibited D-gal-induced up-regulation of natriuretic peptides A (ANP), brain natriuretic peptide (BNP) and ageing markers p53 and p21 in a dose-dependent manner. To further explore the potential mechanisms contributing to the anti-ageing protective effect of AOS, the age-related mitochondrial compromise was analysed. Our data indicated that AOS alleviated D-gal-induced cardiac ageing by improving mitochondrial biogenesis, maintaining the mitochondrial integrity and enhancing the efficient removal of impaired mitochondria. AOS also decreased the ROS production and oxidative stress status, which, in turn, further inhibiting cardiac mitochondria from being destroyed. Together, these results demonstrate that AOS may be an effective therapeutic agent to alleviate cardiac ageing.

Alginate Oligosaccharide Ameliorates D-Galactose-Induced Kidney Aging in Mice through Activation of the Nrf2 Signaling Pathway.

Aging is an independent risk factor for the development of age-related progressive kidney injury. As a part of the aging process, kidney aging has been indicated to be associated with oxidative stress-induced damage. Ameliorating oxidative damage is therefore considered a promising strategy for delaying kidney aging. Alginate oligosaccharide (AOS) has been reported to have a wide range of biological and pharmacological activities. However, no studies have focused on the role of AOS in delaying the kidney aging process. In this study, we aimed to evaluate the potential effects of AOS on kidney aging and its possible mechanisms. Subcutaneous injection of D-galactose (D-gal) (200 mg·kg-1·d-1) in C57BL/6J mice for 8 weeks was used to establish the aging model. AOS (200 mg·kg-1·d-1) was administered via oral gavage for the last four weeks. As a result, AOS inhibited the D-gal-induced upregulation of aging markers and significantly improved the kidney index and kidney function of D-gal-induced mice. In addition, AOS ameliorated the degree of tissue damage and fibrosis in the aging kidney. To further explore the potential mechanisms by which AOS attenuates the kidney aging process, the associated oxidative stress-induced damage was analyzed in depth. The data showed that AOS upregulated the expression of Klotho and decreased malondialdehyde levels by increasing the expression of antioxidant enzymes. Furthermore, our results suggested that AOS activated the nuclear factor erythrogen-2 associated factor 2 (Nrf2) pathway by promoting Nrf2 nuclear translocation in aging mice and upregulated the downstream expression of heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In conclusion, the present study demonstrated that AOS is a promising agent for attenuating kidney aging, and the underlying molecular mechanisms are related to the activation of the Nrf2 signaling pathway.

Alginate Oligosaccharide Prevents against D-galactose-mediated Cataract in C57BL/6J Mice via Regulating Oxidative Stress and Antioxidant System.

PURPOSE: Alginate oligosaccharides (AOS), obtained from depolymerizing alginate, has multiple pharmacological benefits. Cataract is a common disease caused by turbidity of the lens protein due to lens metabolism disorders. This study aimed to test the effects and the underlying mechanisms of AOS on D-galactose (D-gal)-mediated cataract. MATERIALS AND METHODS: A total of 45 8-week-old C57BL/6 J male mice were randomly divided into 5 groups. After eight weeks' intervention, the score of cataract was calculated depending on the turbidity of the lens. Hematoxylin and eosin (HE) and transmission electron microscope (TEM) images were observed. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were measured by corresponding detection kits, respectively. SOD1, SOD2, catalase (CAT) and p53 protein expressions were examined by Western blot. Nuclear factor erythroid-2 related factor (Nrf2) and heme oxygenase-1 (HO-1) mRNA expressions were examined by Quantitative Real Time-PCR (RT-qPCR). RESULTS: The score of the turbidity of the lens showed that AOS significantly delayed the cataractogenesis. HE staining and TEM imaging showed that AOS decreased the damage and senescence of lenses in D-gal-induced C57BL/6 J mice. We further detected aging marker p53 expression in crystalline lenses, and our result showed that AOS significantly inhibited p53 protein expression in D-gal-induced mice. In addition, SOD activity and MDA level detection results showed that AOS significantly increased the activity of SOD, and decreased the level of MDA in crystalline lenses homogenates of D-gal-induced aging mice. Western blot results showed that AOS attenuated the damage of D-gal in the protein expressions of antioxidative enzymes SOD1, SOD2 and CAT. RT-qPCR results showed that AOS suppressed the down-regulation of Nrf2 and HO-1 mRNA expressions induced by D-gal. CONCLUSIONS: AOS prevents against D-gal-mediated cataract in C57BL/6 J mice via inhibiting oxidative stress and up-regulating antioxidant system. Consequently, our results suggest that AOS may be an effective therapeutic strategy against cataract.

Alginate oligosaccharide protects endothelial cells against oxidative stress injury via integrin-α/FAK/PI3K signaling.

Alginate oligosaccharide (AOS) was reported to possess antioxidant and free radical scavenging activities, but the specific effects and mechanisms remain unclear. We investigated the effects of AOS on H2O2-induced oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs) and the associated mechanisms. HUVECs were treated with 100-800 µM hydrogen peroxide (H2O2) for various periods (12, 24, and 36 h) to establish an in vitro oxidative stress and apoptosis HUVEC model. AOS protects HUVEC cells against oxidative stress-induced apoptosis by decreasing the expression levels of caspase 3 and Bax, and increasing Bcl-2 expression. Microarray assay, real-time PCR and western blot results revealed that AOS was able to effectively suppress H2O2-induced apoptosis via regulated integrin-α/FAK/PI3K pathway by influencing the expression of integrin-α, FAK, PI3K, PTEN, P21, and CDK2. In conclusion, our study suggests that AOS can protect endothelial cells against oxidative stress injury caused by H2O2, providing novel alternative strategies to prevent atherosclerosis in the future.

Correlation between sarcopenia and left ventricular myocardial mass in chronic heart failure patients.

Sarcopenia is defined as a progressive age-related syndrome of reduced whole-body muscle mass, muscle strength, and muscle function. Patients with heart failure (HF) and sarcopenia are inclined to have decreased muscle strength. The current research suggests that skeletal muscle changes are the main manifestations of sarcopenia, but myocardium is not mentioned as skeletal muscle. The myocardium changes significantly with the progression of HF. Measuring myocardial quality has become an important and accessible way to assess HF by detecting changes in myocardial quality in patients with sarcopenia. Due to its economical, simple, and effective advantages in measuring myocardial quality, real-time three-dimensional echocardiography provides a convenient and reliable method for clinical diagnosis of HF and sarcopenia. This will be conducive to the screening of sarcopenia in people with chronic HF to better guide clinical treatments. This review describes the definition and diagnostic criteria of sarcopenia, the characteristics of HF with sarcopenia, and the related study of myocardial quality.

Diffusion-weighted imaging-documented bilateral small embolic stroke involving multiple vascular territories may indicate occult cancer: A retrospective case series and a brief review of the literature.

Diffusion-weighted imaging (DWI) MRI is very sensitive for detecting small embolic brain infarctions. Stroke as the first manifestation of cancer is extremely rare. We performed a retrospective study to identify the clinical and DWI features of patients with acute ischemic stroke as the first manifestation of occult cancer. A total of five patients in our hospital from January 2017 to May 2019 were analyzed. We also reviewed the literature and seven case series (16 patients) were included. Most of these patients were aged in their sixties and lung cancer was the most common type of occult cancer. Patients showed various presentations of ischemic stroke. All of the patients showed small multiple lesions on DWI that involved mostly the anterior or both anterior and posterior territories. The lesions were mostly in both the supratentorium and infratentorium, with the mechanisms of embolic and watershed infarcts. These features were useful for identifying the causes of embolic stroke. Therefore, patients with small bilateral embolic stroke, especially those involved in multiple vascular territories, should be examined for concealed malignancy.

Alginate Oligosaccharide Alleviates Monocrotaline-Induced Pulmonary Hypertension via Anti-Oxidant and Anti-Inflammation Pathways in Rats.

Pulmonary arterial hypertension (PAH) is a serious and fatal cardiovascular disorder characterized by increased pulmonary vascular resistance and progressive pulmonary vascular remodeling. The underlying pathological mechanisms of PAH are multi-factorial and multi-cellular. Alginate oligosaccharide (AOS), which is produced by depolymerizing alginate, shows better pharmacological activities and beneficial effects. The present study was undertaken to investigate the effects and potential mechanisms of AOS-mediated alleviation of pulmonary hypertension. Pulmonary hypertension was induced in Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg). Five weeks after the injection of MCT, AOS (5, 10, and 20 mg·kg-1·d-1) was injected intraperitoneally for another three weeks. The results showed that AOS prevented the development of MCT-induced pulmonary hypertension and right ventricular hypertrophy in a dose-dependent manner. AOS treatment also prevented MCT-induced pulmonary vascular remodeling via inhibition of the TGF-ß1/p-Smad2 signaling pathway. Furthermore, AOS treatment downregulated the expression of malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, and pro-inflammatory cytokines, decreased macrophage infiltration, and upregulated the expression of anti-inflammatory cytokines. These findings indicate that AOS exerts anti-oxidative and anti-inflammatory effects in pulmonary arteries, which may contribute to the alleviation of pulmonary hypertension and pulmonary vascular remodeling.

Effects and mechanisms of PSS-loaded nanoparticles on coronary microcirculation dysfunction in streptozotocin-induced diabetic cardiomyopathy rats.

Coronary microvascular dysfunction (CMD) is the pathological basis and pathogenesis of diabetic cardiomyopathy (DCM). Propylene glycol alginate sodium sulfate (PSS) as heparinoid drug has many biological activities. Here, a novel PSS-loaded nanoparticle (PSS-NP) was prepared to study its effect on the CMD of DCM. We used diabetes mellitus rat induced by STZ to establish the CMD model of DCM, and the study was detected by echocardiography, histological analysis, transmission electron microscopy, immunofluorescence staining, enzyme-linked immunosorbent assay, real time-PCR analysis, liquid-chip analysis, western blot analysis and so on. The experimental results suggested that PSS-NP could improve the survival state of rats, cardiac function, myocardial morphology and coronary microcirculation structure disorders, and increase the number of microvessels. In addition, we demonstrated that PSS-NP could alleviate the CMD by improving endothelial function, anticoagulation and antioxidative stress. The outcomes of this study provided new treatment thoughts for the therapy of coronary microcirculation dysfunction in DCM.

Syndecan-1 suppresses cell growth and migration via blocking JAK1/STAT3 and Ras/Raf/MEK/ERK pathways in human colorectal carcinoma cells.

BACKGROUND: Syndecan-1 (SDC-1) is a crucial membrane proteoglycan, which is confirmed to participate in several tumor cell biological processes. However, the biological significance of SDC-1 in colorectal carcinoma is not yet clear. An objective of this study was to investigate the role of SDC-1 in colorectal carcinoma cells. METHODS: Expression of SDC-1 in colorectal carcinoma tissues was evaluated by Reverse transcription-quantitative real-time PCR (RT-qPCR) and western blot. After transfection with pcDNA3.1 or pc-SDC-1, the transfection efficiency was measured. Next, SW480, SW620 and LOVO cell viability, apoptosis, migration and adhesion were assessed to explore the effects of exogenous overexpressed SDC-1 on colorectal carcinoma. In addition, the influences of aberrant expressed SDC-1 in Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) and rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways were detected by western blot analysis. RESULTS: SDC-1 mRNA and protein levels were down-regulated in human colorectal carcinoma tissues. SDC-1 overexpression inhibited cell proliferation via suppressing CyclinD1 and c-Myc expression, meanwhile stimulated cell apoptosis via increasing the expression levels of B-cell lymphoma-2-associated x (Bax) and Cleaved-Caspase-3. Additionally, SDC-1 overexpression restrained cell migration via inhibiting the protein expression of matrix metallopeptidase 9 (MMP-9), and elicited cell adhesion through increasing intercellular cell adhesion molecule-1 (ICAM-1). Furthermore, SDC-1 overexpression suppressed JAK1/STAT3 and Ras/Raf/MEK/ERK-related protein levels. CONCLUSIONS: In general, the evidence from this study suggested that SDC-1 suppressed cell growth, migration through blocking JAK1/STAT3 and Ras/Raf/MEK/ERK pathways in human colorectal carcinoma cells.