638,724 results match your criteria degradation vivo

Platinum complexes inhibit HER-2 enriched and triple-negative breast cancer cells metabolism to suppress growth, stemness and migration by targeting PKM/LDHA and CCND1/BCL2/ATG3 signaling pathways.

Eur J Med Chem 2021 Jul 7;224:113689. Epub 2021 Jul 7.

Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, School of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010021, PR China. Electronic address:

Triple-negative-breast cancer (TNBC) and HER-2 enriched positive aggressive types of breast cancer and are highly metastatic in nature. Anticancer agents those target TNBC and HER-2 enriched positive breast cancers are considered important in the field of breast cancer research. In search of the effective anticancer agents, we synthesized Pt(II) complexes to target these cancers. Read More

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Nicotinamide phosphoribosyltransferase inhibitors selectively induce apoptosis of AML stem cells by disrupting lipid homeostasis.

Cell Stem Cell 2021 Jul 12. Epub 2021 Jul 12.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, ON, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, Toronto, ON, Canada. Electronic address:

Current treatments for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), which perpetuate the disease. Here, we performed a metabolic drug screen to identify LSC-specific vulnerabilities and found that nicotinamide phosphoribosyltransferase (NAMPT) inhibitors selectively killed LSCs, while sparing normal hematopoietic stem and progenitor cells. Treatment with KPT-9274, a NAMPT inhibitor, suppressed the conversion of saturated fatty acids to monounsaturated fatty acids, a reaction catalyzed by the stearoyl-CoA desaturase (SCD) enzyme, resulting in apoptosis of AML cells. Read More

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Age-Dependent Changes in Total and Free Water Content of In Vivo Human Lenses Measured by Magnetic Resonance Imaging.

Invest Ophthalmol Vis Sci 2021 Jul;62(9):33

Department of Physiology, School of Medical Sciences, New Zealand National Eye Centre, University of Auckland, New Zealand.

Purpose: To use magnetic resonance imaging (MRI) to measure age-dependent changes in total and free water in human lenses in vivo.

Methods: Sixty-four healthy adults aged 18 to 86 years were recruited, fitted with a 32-channel head receiver coil, and placed in a 3 Tesla clinical MR scanner. Scans of the crystalline lens were obtained using a volumetric interpolated breath-hold examination sequence with dual flip angles, which were corrected for field inhomogeneity post-acquisition using a B1-map obtained using a turbo-FLASH sequence. Read More

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Replenishment of TCA cycle intermediates provides photoreceptor resilience against neurodegeneration during progression of retinitis pigmentosa.

JCI Insight 2021 Jul 22. Epub 2021 Jul 22.

Department of Ophthalmology, UT Southwestern Medical Center, Dallas, United States of America.

The metabolic environment is important for neuronal cells, such as photoreceptors. When photoreceptors undergo degeneration, as occurs during retinitis pigmentosa (RP), patients have progressive loss of vision that proceeds to full blindness. Currently, there are no available treatments for the majority of RP diseases. Read More

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Colon-Targeted Adhesive Hydrogel Microsphere for Regulation of Gut Immunity and Flora.

Adv Sci (Weinh) 2021 Jul 22:e2101619. Epub 2021 Jul 22.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.

Intestinal immune homeostasis and microbiome structure play a critical role in the pathogenesis and progress of inflammatory bowel disease (IBD), whereas IBD treatment remains a challenge as the first-line drugs show limited therapeutic efficiency and great side effect. In this study, a colon-targeted adhesive core-shell hydrogel microsphere is designed and fabricated by the ingenious combination of advanced gas-shearing technology and ionic diffusion method, which can congregate on colon tissue regulating the gut immune-microbiota microenvironment in IBD treatment. The degradation experiment indicates the anti-acid and colon-targeted property of the alginate hydrogel shell, and the in vivo imaging shows the mucoadhesive ability of the thiolated-hyaluronic acid hydrogel core of the microsphere, which reduces the systematic exposure and prolongs the local drug dwell time. Read More

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Salidroside activates the AMP-activated protein kinase pathway to suppress non-alcoholic steatohepatitis.

Hepatology 2021 Jul 22. Epub 2021 Jul 22.

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is becoming a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Salidroside (p-hydroxyphenethyl-β-d-glucoside) has various biological and pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. However, the therapeutic effect and underlying molecular mechanism of salidroside in NASH remain to be further clarified. Read More

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Hypoxia and glucose metabolism assessed by FMISO and FDG PET for predicting IDH1 mutation and 1p/19q codeletion status in newly diagnosed malignant gliomas.

EJNMMI Res 2021 Jul 21;11(1):67. Epub 2021 Jul 21.

Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Miki-cho, Kagawa, Japan.

Background: Tumor hypoxia and glycolysis have been recognized as determinant factors characterizing tumor aggressiveness in malignant gliomas. To clarify in vivo hypoxia and glucose metabolism in relation to isocitrate dehydrogenase (IDH) mutation and chromosome 1p and 19q (1p/19q) codeletion status, we retrospectively analyzed hypoxia as assessed by positron emission tomography (PET) with [F]-fluoromisonidazole (FMISO) and glucose metabolism as assessed by PET with [F]-fluoro-2-deoxy-D-glucose (FDG) in newly diagnosed malignant gliomas.

Methods: In total, 87 patients with newly diagnosed supratentorial malignant (WHO grade III and IV) gliomas were enrolled in this study. Read More

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Mathematical Model Predicts that Acceleration of Diabetic Wound Healing is Dependent on Spatial Distribution of VEGF-A mRNA (AZD8601).

Cell Mol Bioeng 2021 Aug 15;14(4):321-338. Epub 2021 Jun 15.

Department of Biomedical Engineering, University of Virginia, Charlottesville, VA USA.

Introduction: Pharmacologic approaches for promoting angiogenesis have been utilized to accelerate healing of chronic wounds in diabetic patients with varying degrees of success. We hypothesize that the distribution of proangiogenic drugs in the wound area critically impacts the rate of closure of diabetic wounds. To evaluate this hypothesis, we developed a mathematical model that predicts how spatial distribution of VEGF-A produced by delivery of a modified mRNA (AZD8601) accelerates diabetic wound healing. Read More

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Enhancement of E-cadherin expression and processing and driving of cancer cell metastasis by ARID1A deficiency.

Oncogene 2021 Jul 21. Epub 2021 Jul 21.

Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical of Sciences, Fudan University, Shanghai, China.

The ARID1A gene, which encodes a subunit of the SWI/SNF chromatin remodeling complex, has been found to be frequently mutated in many human cancer types. However, the function and mechanism of ARID1A in cancer metastasis are still unclear. Here, we show that knockdown of ARID1A increases the ability of breast cancer cells to proliferate, migrate, invade, and metastasize in vivo. Read More

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Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice.

Commun Biol 2021 Jul 21;4(1):894. Epub 2021 Jul 21.

Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan.

Mitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Read More

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IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer.

NPJ Breast Cancer 2021 Jul 21;7(1):95. Epub 2021 Jul 21.

Department of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.

Breast cancer bone metastasis is currently incurable, ~75% of patients with late-stage breast cancer develop disease recurrence in bone and available treatments are only palliative. We have previously shown that production of the pro-inflammatory cytokine interleukin-1B (IL-1B) by breast cancer cells drives bone metastasis in patients and in preclinical in vivo models. In the current study, we have investigated how IL-1B from tumour cells and the microenvironment interact to affect primary tumour growth and bone metastasis through regulation of the immune system, and whether targeting IL-1 driven changes to the immune response improves standard of care therapy for breast cancer bone metastasis. Read More

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Lactate secreted by PKM2 upregulation promotes Galectin-9-mediated immunosuppression via inhibiting NF-κB pathway in HNSCC.

Cell Death Dis 2021 Jul 21;12(8):725. Epub 2021 Jul 21.

Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, 200011, Shanghai, China.

Pyruvate kinase M2 as a key rate-limiting enzyme in glycolysis, it plays a critical role in metabolic reprogramming and carcinogenesis. However, whether PKM2 can promote immunosuppressive microenvironment formation remains unknown in head and neck squamous cell carcinoma (HNSCC). PKM2 expression was detected using immunohistochemical staining. Read More

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mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism.

J Immunol 2021 Jul 21. Epub 2021 Jul 21.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD;

Metabolic programming is integrally linked to immune cell function. Nowhere is this clearer than in the differentiation of macrophages. Proinflammatory M1 macrophages primarily use glycolysis as a rapid energy source but also to generate antimicrobial compounds, whereas alternatively activated M2 macrophages primarily rely on oxidative phosphorylation for the longevity required for proper wound healing. Read More

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Erythropoietin promotes abdominal aortic aneurysms in mice through angiogenesis and inflammatory infiltration.

Sci Transl Med 2021 Jul;13(603)

Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, but the underlying mechanisms remain unknown. Here, we tested the hypothesis that erythropoietin (EPO) may promote the formation of AAA. We found that EPO dose-dependently promoted the formation of AAA in both (66. Read More

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Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system.

Moein Ala

Int Rev Immunol 2021 Jul 22:1-20. Epub 2021 Jul 22.

School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

Tryptophan is an essential amino acid, going through three different metabolic pathways in the intestines. Indole pathway in the gut microbiota, serotonin system in the enterochromaffin cells and kynurenine pathway in the immune cells and intestinal lining are the three arms of tryptophan metabolism in the intestines. Clinical, in vivo and in vitro studies showed that each one of these arms has a significant impact on IBD. Read More

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Co-delivery of paclitaxel and STAT3 siRNA by a multifunctional nanocomplex for targeted treatment of metastatic breast cancer.

Acta Biomater 2021 Jul 18. Epub 2021 Jul 18.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. Herein, a multifunctional nanocomplex was developed to simultaneously deliver paclitaxel (PTX) and STAT3 siRNA (siSTAT3) to inhibit tumor growth and prevent metastasis of breast tumor cells. Read More

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Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer.

Cell Rep 2021 Jul;36(3):109394

Bayer AG, Research & Development, Pharmaceuticals, 13353 Berlin, Germany; Nuvisan Innovation Campus Berlin GmbH, 13353 Berlin, Germany.

Novel treatment options for metastatic colorectal cancer (CRC) are urgently needed to improve patient outcome. Here, we screen a library of non-characterized small molecules against a heterogeneous collection of patient-derived CRC spheroids. By prioritizing compounds with inhibitory activity in a subset of-but not all-spheroid cultures, NCT02 is identified as a candidate with minimal risk of non-specific toxicity. Read More

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CD142 plays a key role in the carcinogenesis of gastric adenocarcinoma by inhibiting BCL2-dependent autophagy.

Biochem Cell Biol 2021 Jul 21. Epub 2021 Jul 21.

Henan Cancer Hospital, 377327, Zhengzhou, China, 450008;

CD142 is expressed on the surface of multiple malignant tumors and contributes to various carcinogenesis. However, the role of CD142 in the pathogenesis of GAC remains unclear. This study aimed to investigate the role of CD142 in GAC carcinogenesis. Read More

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Alantolactone is a natural product that potently inhibits YAP1/TAZ via promotion of ROS accumulation.

Cancer Sci 2021 Jul 21. Epub 2021 Jul 21.

Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan.

YAP1 and its paralogue TAZ play pivotal roles in cell proliferation, migration and invasion, and abnormal activation of these TEAD transcriptional co-activators is found in diverse cancers in humans and mice. Targeting YAP1/TAZ signaling is thus a promising therapeutic avenue but, to date, few selective YAP1/TAZ inhibitors have been effective against cancer cells either in vitro or in vivo. We screened chemical libraries for potent YAP1/TAZ inhibitors using a highly sensitive luciferase reporter system to monitor YAP1/TAZ-TEAD transcriptional activity in cells. Read More

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A Roadmap to the Structure-Related Metabolism Pathways of Per- and Polyfluoroalkyl Substances in the Early Life Stages of Zebrafish ().

Environ Health Perspect 2021 Jul 21;129(7):77004. Epub 2021 Jul 21.

Department of Chemistry, University of Toronto, Toronto, Ontario, Canada.

Background: Thousands of per- and polyfluoroalkyl substances (PFAS) with diverse structures have been detected in the ambient environment. Apart from a few well-studied PFAS, the structure-related toxicokinetics of a broader set of PFAS remain unclear.

Objectives: To understand the toxicokinetics of PFAS, we attempted to characterize the metabolism pathways of 74 structurally diverse PFAS samples from the U. Read More

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FUBP1 promotes colorectal cancer stemness and metastasis via DVL1-mediated activation of Wnt/β-catenin signaling.

Mol Oncol 2021 Jul 20. Epub 2021 Jul 20.

Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

Distant metastasis is, unfortunately, the leading cause of death in colorectal cancer (CRC). Approximately 50% of CRC patients develop liver metastases, while 10-30% of patients develop pulmonary metastases. The occurrence of metastasis is considered to be almost exclusively driven by cancer stem cells (CSCs) formation. Read More

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UCHL1 regulates inflammation via MAPK and NF-κB pathways in LPS-activated macrophages.

Cell Biol Int 2021 Jul 20. Epub 2021 Jul 20.

Department of Emergency, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.

Inflammation is a common pathophysiological process as well as a clinical threat that occurs in various diseases worldwide. It is well-documented that nuclear factor-κB (NF-κB) and mitogen-activated protein kinase pathways are involved in inflammatory reactions to microbial infections in lipopolysaccharide (LPS)-activated macrophages. The deubiquitinase ubiquitin carboxyl-terminal hydrolase-L1 (UCHL1) has been reported as an oncoprotein to promote the growth and progression of cancer cells. Read More

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Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications.

Noncoding RNA 2021 Jul 7;7(3). Epub 2021 Jul 7.

Department of Medicine, Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York, NY 10461, USA.

Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 partakes in the phenotypic switch of cells within the islets of Langerhans under metabolic stress. Read More

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Reactive oxygen species in cancer: current findings and future directions.

Cancer Sci 2021 Jul 19. Epub 2021 Jul 19.

Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Reactive oxygen species (ROS), a class of highly bioactive molecules, have been widely studied in various types of cancers. ROS are considered to be normal byproducts of numerous cellular processes. Typically, cancer cells exhibit higher basal levels of ROS compared to normal cells as a result of an imbalance between oxidants and antioxidants. Read More

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synthesis of fluorescent polydopamine on biogenic MnO nanoparticles as stimuli responsive multifunctional theranostics.

Biomater Sci 2021 Jul 21. Epub 2021 Jul 21.

School of Chemistry and Chemical Engineering, Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, Huazhong University of Science and Technology, Wuhan 430074, China.

Multifunctional nanocomposites have drawn great attention in clinical applications because of their ability to integrate diagnostic and therapeutic functions. Manganese dioxide (MnO2), owing to its biocompatibility and magnetic resonance imaging (MRI) properties, has been widely applied in biomedical research. Our previous work on biogenic MnO2 nanoparticles (Bio-MnO2 NPs) revealed that intrinsic photothermal properties and stimuli-responsive MRI imaging are particularly promising for the development of theranostic systems. Read More

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TPGS-Galactose-Modified Polydopamine Co-delivery Nanoparticles of Nitric Oxide Donor and Doxorubicin for Targeted Chemo-Photothermal Therapy against Drug-Resistant Hepatocellular Carcinoma.

ACS Appl Mater Interfaces 2021 Jul 21. Epub 2021 Jul 21.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.

The lack of cancer cell specificity and the occurrence of multidrug resistance (MDR) are two major obstacles in the treatment of hepatocellular carcinoma (HCC). To tackle these challenges, a novel nanoparticle (NP)-based drug delivery system (DDS) with a core/shell structure consisted of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-galactose (Gal)/polydopamine (PDA) is fabricated. The NP is loaded with doxorubicin (DOX) and a nitric oxide (NO) donor ,'-di--butyl-,'-dinitroso-1,4-phenylenediamine (BNN) sensitive to heat to afford [email protected] Read More

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A Review on Antidiabetic Activity of spp.: A New Approach for Developing Herbal Remedies.

Evid Based Complement Alternat Med 2021 5;2021:5587938. Epub 2021 Jul 5.

Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Objective: Diabetes mellitus (DM) is a long-life metabolic disorder, characterized by high blood glucose levels. The hyperglycemic condition generally leads to irreversible nerve injury and vascular damage. Among different types of diabetes, type 2 is more common and has spread all over the world. Read More

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Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway.

J Inflamm Res 2021 12;14:3129-3143. Epub 2021 Jul 12.

Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, People's Republic of China.

Background: Retinal pigment epithelium (RPE) cellular senescence is an important process in degenerative retinal disorders. Grape seed proanthocyanidin extract (GSPE) alleviates senescence-related degenerative disorders; however, the potential effects of GSPE intake on RPE cellular senescence through regulating NAMPT/SIRT1/NLRP3 pathway remain unclear.

Methods: The effects of GSPE on NAMPT expression and NAD+ contents were detected with Western blot and assay kit in both in-vivo and in-vitro AMD models. Read More

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Alisol B 23-acetate, a new promoter for cholesterol efflux from dendritic cells, alleviates dyslipidemia and inflammation in advanced atherosclerotic mice.

Int Immunopharmacol 2021 Jul 18;99:107956. Epub 2021 Jul 18.

School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing 210023, China. Electronic address:

Atherosclerosis (AS) is characterized by dyslipidemia and chronic inflammation. In the high-fat environment, the lipid metabolism of dendritic cells (DCs) is abnormal, which leads to abnormal immune function, promotes the occurrence of immune inflammatory reactions, and promotes the development of AS. Alisol B 23-acetate (23B) is a triterpenoid in the rhizomes of Alisma, which is a traditional Chinese medicine. Read More

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PINCH-1 promotes Δ-pyrroline-5-carboxylate synthase expression and contributes to proline metabolic reprogramming in lung adenocarcinoma.

Amino Acids 2021 Jul 20. Epub 2021 Jul 20.

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.

Proline metabolic reprogramming is intimately involved in cancer progression. We recently identified a critical role of PINCH-1, a cell-extracellular matrix (ECM) adhesion protein whose expression is elevated in lung adenocarcinoma, in the promotion of proline biosynthesis, fibrosis and lung adenocarcinoma growth. How PINCH-1 promotes proline biosynthesis, however, was incompletely understood. Read More

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