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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.

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/β-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/β-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/β-catenin signaling. Targeting BRD7 may become a promising therapeutic strategy for the treatment of MI-induced myocardial injury.

Tucatinib (1, Scheme 1), also named as irbinitinib, ARRY-380 or ONT-380, marketed as TukysaTM, is an oral inhibitor of HER2 (human epidermal growth factor receptor tyrosine kinase ErbB-2) with anti...

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., The mechanisms of vascular aging include inflammation, mitochondrial dysfunction and oxidative stress, telomere attrition, epigenetics and autophagy.

We herein disclose the first Ni-catalyzed Hiyama coupling of aryl halides with vinylsilanes. This protocol uses cheap, nontoxic, and stable vinyltrimethoxysilane as the vinyl donor, proceeds under mild and ligand-free conditions, furnishing a diverse variety of styrene derivatives in high yields with excellent functional group compatibility.

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.

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.To investigate whether APS can attenuate cardiac hypertrophy in DCM and exert anti-hypertrophic effects by inhibiting the bone morphogenetic protein 10 (BMP10) pathway.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.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.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.

As a very important basic industrial chemical, m-dinitrobenzene (m-DNB) is widely used in the pesticide, photosensitive materials, printing and dyeing industries.1 Its derivatives, as shown in Sche...

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-1β, 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.

Metamifop (1, Figure 1), developed by the Korea Research Institute of Chemical Technology, is a post-emergent aryloxyphenoxypropionic herbicide, and only the R-isomer has bioactivity. It is mainly ...

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.

To propagate emergent spacecraft’s flight state, the ephemeris should be determined first. This paper proposes two kinds of algorithms to solve this problem. Primarily, an iteration algorithm based on single navigation data is proposed. Since it is not able to figure out drag coefficient with iteration algorithm, and it is vulnerable to measurement noise, the filter algorithms including Extended Kalman filter and Unscented Kalman filter based on multiple navigation data are established. Both kinds of algorithms are related to SGP4 model, which must use two line elements as inputs to predict position and velocity. Simulations and results show that both algorithms can determine ephemeris effectively and quickly. As for the precision of the iteration algorithm, the propagation deviations are within 1 m for position and 10–3 m/s for velocity within 1 day on three axes when there is no measurement noise. The precision of filter algorithm results is at least 10–5 degree for the four angles, 10–7 for eccentricity, 10–9 Rev/Day for mean motion, and 10–6 for drag coefficient when the measurement noise is 10 m. Use TLEs determined by EKF and UKF to propagate; the position and velocity deviations are within 5 m and 0.005 m/s within 1 day, respectively. Iteration algorithm’s effect becomes poor when measurement noise is added. In contrast, EKF and UKF can eliminate noise’s influence. EKF performs better than UKF under small measurement noise and big initial error condition, whereas under big noise condition, UKF performs better than EKF. Since all the results are convergent to the required precision of TLEs’ format, both approaches can be applied to emergent spacecraft ephemeris determination mission.

As an important organic chemical and pharmaceutical intermediate, m-aminophenol (1, Figure 1) is widely used in the pesticide, medicinal, printing and dyeing industries. As examples, it can be used...

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.

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-β1/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.

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.

Acute myocardial infarction (AMI) is a serious heart disease and the main reason for heart failure and sudden death worldwide. This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on AMI in vitro and in vivo, as well as the underlying mechanisms.Human cardiac microvascular endothelial cells (HCMVEC) were cultured in vitro in an oxygen-glucose deprivation (OGD) environment to induce injury. The viability and apoptosis of HCMVEC were then detected using CCK-8 assay and Annexin V-FITC/PI staining, respectively. ELISA was performed to measure the concentrations of inflammatory cytokines. Cell transfection was conducted to reduce the expression of HIF-1α. Expression of key factors involving in cell proliferation, apoptosis, autophagy, MEK/ERK, and the NF-κB and mTOR pathways were evaluated using Western blotting. In vivo, Wistar rats were pre-treated by PEP and AMI was induced. The infarct size and cardiac functions (LVEDD, LVEF and LVFS) were measured.In vitro, PEP treatment significantly protected HCMVEC from OGD-induced viability loss, proliferation inhibition, apoptosis, inflammatory cytokine expression, and autophagy. Moreover, PEP enhanced the expression of HIF-1α in HCMVEC via the MEK/ERK pathway. HIF-1α participated in the protective effects of PEP on OGD-treated HCMVEC. Furthermore, PEP attenuated OGD-induced NF-κB pathway activation and promoted the mTOR pathway in HCMVEC. In vivo, PEP pre-treatment reduced the infarct size and enhanced the LVEDD, LVEF and LVFS of rats via up-regulation of HIF-1α.PEP ameliorated AMI in vitro and in vivo through up-regulation of HIF-1α. In vitro, PEP could activate the MEK/ERK and mTOR pathways, but inactivate the NF-κB pathway in OGD-treated HCMVEC.

A new and improved synthetic route to tucatinib is described that involves three key intermediates. The first of these, 4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylaniline, was prepared on a 100 g scale in 33% yield over five steps and 99% purity. Next, N 4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)quinazoline-4,6-diamine was isolated in 67% yield over three steps and >99% purity. Then, 4,4-dimethyl-2-(methylthio)-4,5-dihydrooxazole trifluoromethanesulfonate was prepared under mild conditions in 67% yield over two steps. Finally, tucatinib was obtained in 17% yield over nine steps and in >99% purity (HPLC). Purification methods used to isolate the product and the intermediates involved in the route are also reported.

Perivascular inflammation, vascular luminal area reduction and hemodynamics changes are important pathophysiologic bases of pulmonary hypertension (PH). In this study, PH was induced by an intraperitoneal single injection of monocrotaline (MCT, 60 mg/kg). Alginate oligosaccharides (AOS), one of the most famous marine drugs, provided protections in the perivascular inflammation, vascular luminal area reduction and hemodynamics changes of the PH rat induced by MCT. The downregulation of P-selectin plays an important role in the protective effects of AOS against MCT induced PH. The results showed that the treatment with AOS (5, 10, or 20 mg/kg) dose-dependently decreased the expression of P-selectin in serum, pulmonary tissue and pulmonary artery of MCT-induced pulmonary arterial hypertension rats. What’s more, the study showed that the protective effects were mediated by the inhibition of p38MAPK/NF-κB pathway, which was caused by reducing the p-p38MAPK protein expression, IκBα degradation and nuclear transcription of NF-κB protein in the pulmonary artery of MCT-induced PH rats. These findings provided an alternative potent medicine for the prevention and therapy of PH.

Propylene glycol alginate sodium sulfate-loaded nanoparticles (PSS-NP) has been shown potential to prevent the microvascular endothelial injuries caused by diabetic cardiomyopathy (DCM). In this study, we aimed to investigate the effects of PSS-NP on the dysfunction of cardiac microvascular endothelia in streptozotocin (STZ)-induced DCM rat model. Echocardiographic measurements showed a significant improvement of cardiac function in the PSS-NP-treated group. Our results revealed that the abnormalities of cardiac systolic and diastolic functions were suppressed by the treatments of prostaglandin E1 (PGE1), low molecular weight heparin (LMWH), PSS and PSS-NP. Our comparison analysis indicated that PSS-NP showed the strongest inhibitory effects on microvascular endothelial injuries. Transmission electron microscopy analysis demonstrated that PSS-NP protected the cardiac microvascular endothelium and further improved endothelium dysfunction in DCM rats. ELISA and Western blot assays further showed a high efficiency of improving cardiac microvascular endothelial dysfunction with PSS-NP. Our results demonstrated that PSS-NP increased the protein expression of phosphatidylinositol 3-kinase (PI3K)-p85 and vascular endothelial growth factor (VEGF)-A, and the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS), which were involved in the amelioration of cardiac microvascular endothelial dysfunction. These data suggest that PSS-NP may be a novel approach to the treatment the coronary microcirculation disorder diseases such as DCM.

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.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) imagesThe 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.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 (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.

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.

An error appeared in the article entitled "Polysaccharides from Enteromorpha Prolifera Ameliorate Acute Myocardial Infarction in Vitro and in Vivo via Up-Regulating HIF-1α" by Zongqiu Wang, Zhihua Zhang, Jing Zhao, Chunming Yong, and Yongjun Mao (Vol. 60, No. 4, 964-973, 2019).The second affiliation of the authors on the bottom of page 964 should be replaced by "

A new, practical, and convergent synthetic route of gedatolisib, an antitumor agent, is developed on a hectogram scale which avoids the Pd coupling method. The key step is adopting 6-(4-nitrophenyl)-1,3,5-triazine-2,4-diamine and 2,2′-dichlorodiethyl ether to prepare the key 4,4′-(6-(4-nitrophenyl)-1,3,5-triazine-2,4-diyl)dimorpholine in 77% yield and 98.8% purity. Gedatolisib is obtained in 48.6% yield over five simple steps and 99.3% purity (HPLC). Purification methods of the intermediates and the final product involved in the route are given.

New and practical synthetic route of ivacaftor is described on a grams scale. An electrophilic addition of two t-butyl groups to the aromatic ring is adopted to prepare 5-amino-2,4-di-t-butylphenol in 61% yield over three steps with 98.1% purity (high-performance liquid chromatography). An intramolecular cyclization of ethyl 3-(2-aminophenyl)-3-oxo-propanoate with dimethylformamide-dynamic mechanical analysis is used to prepare 4-oxo-1,4-dihydroquinoline-3-carboxylic acid in 54% yield over four steps. Ivacaftor is obtained by condensation of the two parts in 71% yield with 99.1% purity (high-performance liquid chromatography).

New and practical synthetic route of momelotinib, a JAK inhibitor, is described on a decagram scale. A convergent synthetic process is adopted to prepare the methyl 4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl) benzoate intermediate, by cyclization of 1-(4-morpholinophenyl)guanidine and methyl 4-(3-(dimethylamino)acryloyl)benzoate in high yield and mild conditions. Momelotinib is obtained in 43.2% yield over five steps and 99.1% purity (HPLC).

BackgroundSyndecan-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.MethodsExpression 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.ResultsSDC-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.ConclusionsIn 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.

Ethnopharmacological relevance Traditional Chinese medicine Astragalus membranaceus (Fisch.) Bunge (AM) has been utilized for the treatment of diabetes mellitus and its complications for centuries. Astragalus polysaccharides (APS), the main bioactive ingredient extracted from the root of AM, is prescribed widely in China and has definite cardioprotective effect during diabetic cardiomyopathy (DCM). Endoplasmic reticulum (ER) stress-induced apoptosis played a crucial role in the progression of DCM. However, the regulatory mechanisms of APS on ER stress pathway haven't been comprehensively studied so far. Aim of the study: The aim of this study was to identify the effect of APS on cardiomyocyte apoptosis and to investigate the mechanisms for the anti-apoptotic effect of APS during DCM. Materials and methods DCM rat model was induced by intraperitoneal streptozotocin (STZ) injection and treated with APS for 16 weeks. Cardiac function, pathological changes and apoptotic cells were assessed by echocardiography, hematoxylin-eosin (HE) staining and TUNEL assay, respectively. Expressions of key molecules in ER stress pathway were detected by Western blot analysis. Cardiomyocytes were exposed to high glucose (HG) and treated with APS for 24 h. Cell viability, apoptosis and protein expressions were assessed by MTT, flow cytometer and Western blot analysis, respectively. Moreover, lentivirus over-expressing (OE) C/EBP homologous protein (CHOP) was employed to further investigate the causative role of ER stress pathway in APS-mediated effect on cardiomyocyte apoptosis. Results In vivo, the results demonstrated that APS could improve heart function and attenuate myocardial apoptosis in DCM rat model. Further study demonstrated that APS could down-regulate the protein expressions of activating transcription factor 6 (ATF6) and protein kinase RNA-like ER kinase (PERK) related factors of ER stress pathway. In vitro, APS significantly inhibit HG stimulated H9C2 cell apoptosis and the expressions of ATF6 and PERK related proteins of ER stress pathway. However, after CHOP-OE lentivirus transfection, the protective effects of APS were diminished as increased apoptotic rate and higher expression of CHOP. Conclusions APS could attenuate cardiomyocyte apoptosis via down-regulating the expression of ATF6 and PERK related factors of ER stress pathway in DCM rats and HG-stimulated H9C2 cells.