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Tranexamic acid and obstetric hemorrhage: give empirically or selectively?

Int J Obstet Anesth 2021 Jun 30;48:103206. Epub 2021 Jun 30.

Department of Obstetrics and Gynecology, Bordeaux University Hospital, University of Bordeaux, Bordeaux, France.

Antifibrinolytic agents such as tranexamic acid (TXA) inhibit the fibrinolytic pathway and protect blood clots from being degraded, thereby promoting hemostasis. They have been used to reduce blood loss in various settings including obstetrics. Based on current evidence, TXA can be considered as a therapeutic adjunct to control postpartum hemorrhage (PPH) after vaginal and cesarean deliveries, with earlier administration preferred. Read More

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Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells.

PLoS One 2021 3;16(8):e0254392. Epub 2021 Aug 3.

Faculty of Medical Science, Department of Physiology, Naresuan University, Phitsanulok, Thailand.

Conventional chemotherapeutic agents for colorectal cancer (CRC) cause systemic side effects and eventually become less efficacious owing to the development of drug resistance in cancer cells. Therefore, new therapeutic regimens have focused on the use of natural products. The anticancer activity of several parts of Calotropis gigantea has been reported; however, the effects of its stem bark extract on inhibition of cancer cell proliferation have not yet been examined. Read More

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Discovery of 3,5-Dimethyl-4-Sulfonyl-1-Pyrrole-Based Myeloid Cell Leukemia 1 Inhibitors with High Affinity, Selectivity, and Oral Bioavailability.

J Med Chem 2021 Aug 3. Epub 2021 Aug 3.

State Key Laboratory of Natural Medicines, and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.

Myeloid cell leukemia 1 (Mcl-1) protein is a key negative regulator of apoptosis, and developing Mcl-1 inhibitors has been an attractive strategy for cancer therapy. Herein, we describe the rational design, synthesis, and structure-activity relationship study of 3,5-dimethyl-4-sulfonyl-1-pyrrole-based compounds as Mcl-1 inhibitors. Stepwise optimizations of hit compound with primary Mcl-1 inhibition (52%@30 μM) led to the discovery of the most potent compound with high affinity ( = 0. Read More

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Nucleomodulin Ank13 Exploits the RaDAR Nuclear Import Pathway To Modulate Host Cell Transcription.

mBio 2021 Aug 3:e0181621. Epub 2021 Aug 3.

Department of Microbiology and Immunology, Virginia Commonwealth University Medical Centergrid.417264.2, School of Medicine, Richmond, Virginia, USA.

Orientia tsutsugamushi is the etiologic agent of scrub typhus, the deadliest of all diseases caused by obligate intracellular bacteria. Nucleomodulins, bacterial effectors that dysregulate eukaryotic transcription, are being increasingly recognized as key virulence factors. How they translocate into the nucleus and their functionally essential domains are poorly defined. Read More

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Porous gelatin microspheres for controlled drug delivery with high hemostatic efficacy.

Colloids Surf B Biointerfaces 2021 Jul 28;207:112013. Epub 2021 Jul 28.

Orthopaedic Oncology Center, Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Effective hemostasis and antibacterial efficacy for extensive trauma in a warzone and civilian accidents are important for reducing mortalities and serious complications. Gelatin has been widely used as a hemostatic agent and has the potential for use in drug delivery systems. To enhance its hemostatic efficiency and create conducive conditions for sustained drug release, we developed Vancomycin-impregnated porous gelatin microspheres (Van-MS) by introducing the porous structure into gelatin. Read More

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Effect of involuntary chronic physical exercise on beta-amyloid protein in experimental models of Alzheimer's disease: Systematic review and meta-analysis.

Exp Gerontol 2021 Jul 30:111502. Epub 2021 Jul 30.

Laboratório de Bioquímica e Expressão Gênica, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.

The excessive deposition of β-amyloid proteins (Aβ) is directly correlated with the establishment and development of Alzheimer's Disease (AD). Current treatments for AD only reduce symptoms instead of acting on Aβ, which is the primary etiological agent. Hence, the anti-amyloid effect of regular exercise has been widely investigated as an alternative therapy. Read More

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DG-8d, a novel diosgenin derivative, decreases the proliferation and induces the apoptosis of A549 cells by inhibiting the PI3k/Akt signaling pathway.

Steroids 2021 Jul 30:108898. Epub 2021 Jul 30.

Qiqihaer Medical University, Heilongjiang Qiqihaer 161006, China. Electronic address:

Lung neoplasm has a relatively poor prognosis, and the clinical efficacy of targeted medicine remains unsatisfactory. Therefore, the development of novel efficient anti-lung cancer drugs is urgently needed. In our previous study, we showed that a novel diosgenin derivative 8d (DG-8d), which contained 5-(3-pyridyl)-1,3,4-thiadiazole moiety, had significant cytotoxic activity on human tumor cells, especially the A549 cells. Read More

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Marine-Derived Xyloketal Compound Ameliorates MPP-Induced Neuronal Injury through Regulating of the IRE1/XBP1 Signaling Pathway.

ACS Chem Neurosci 2021 Aug 2. Epub 2021 Aug 2.

School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China.

The IRE1/XBP1 signaling pathway is the most conserved component of the endoplasmic reticulum unfolded protein response (UPR). Activating this branch to correct defects in ER proteostasis is regarded as a promising anti-Parkinson's disease (PD) strategy. is a marine-derived xyloketal B analog which exhibited potential neuroprotective activities in previous research studies; however, the molecular mechanism underneath its protective effect remains unknown. Read More

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RNA-seq and Experiments Reveal the Protective Effect of Curcumin against 5-Fluorouracil-Induced Intestinal Mucositis via IL-6/STAT3 Signaling Pathway.

J Immunol Res 2021 21;2021:8286189. Epub 2021 Jul 21.

Department of Integrated Traditional Chinese and Western Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang Province 310022, China.

Although first-line chemotherapy drugs, including 5-fluorouracil (5-FU), remain one of the major choice for cancer treatment, the clinical use is also accompanied with dose-depending toxicities, such as intestinal mucositis (IM), in cancer patients undergoing treatment. IM-induced gastrointestinal adverse reactions become frequent reason to postpone chemotherapy and have negative impacts on therapeutic outcomes and prognosis. Various studies have evidenced the anticancer role of curcumin in many cancers; except for this effect, studies also indicated a protective role of curcumin in intestinal diseases. Read More

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Antitumor Effect of Lenvatinib Combined with Alisertib in Hepatocellular Carcinoma by Targeting the DNA Damage Pathway.

Biomed Res Int 2021 22;2021:6613439. Epub 2021 Jul 22.

Department of Hepatobiliary, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Clinical Research Center for Cancer, Tianjin 300070, China.

Methods: Immunohistochemical staining, sequencing, and genetic analysis of liver cancer tissues were performed. The antitumor efficacy of single-agent or combination treatment was measured by cell counting kit-8 assay and colony formation assays. Their antiproliferative and apoptosis activity is evaluated by cell cycle analyses and wound healing assays. Read More

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Pinocembrin Inhibits the Proliferation and Metastasis of Breast Cancer Suppression of the PI3K/AKT Signaling Pathway.

Front Oncol 2021 16;11:661184. Epub 2021 Jul 16.

Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang City, China.

The survival rate of breast cancer (BC) patients remains poor, thus the identification of safe and effective new drugs is crucial to improve therapeutic outcomes and overall survival. Pinocembrin (PCB), a pharmacologically active ingredient of Pinus heartwood, Eucalyptus, Euphorbia, Populus, and Sparattosperma leucanthum, has been widely applied for the treatment of various diseases and possesses anticancer activities. In vitro assays were performed to investigate the antiproliferation and antimetastasis activities of PCB in BC cells. Read More

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Trehalose Augments Neuron Survival and Improves Recovery from Spinal Cord Injury via mTOR-Independent Activation of Autophagy.

Oxid Med Cell Longev 2021 10;2021:8898996. Epub 2021 Jul 10.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Spinal cord injury (SCI) is a major cause of irreversible nerve injury and leads to serious tissue loss and neurological dysfunction. Thorough investigation of cellular mechanisms, such as autophagy, is crucial for developing novel and effective therapeutics. We administered trehalose, an mTOR-independent autophagy agonist, in SCI rats suffering from moderate compression injury to elucidate the relationship between autophagy and SCI and evaluate trehalose's therapeutic potential. Read More

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Polydatin Induces Differentiation and Radiation Sensitivity in Human Osteosarcoma Cells and Parallel Secretion through Lipid Metabolite Secretion.

Oxid Med Cell Longev 2021 20;2021:3337013. Epub 2021 Jul 20.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Osteosarcoma is a bone cancer characterized by the production of osteoid tissue and immature bone from mesenchymal cells. Osteosarcoma mainly affects long bones (femur is most frequently site) and occur in children and young adults with greater incidence. Here, we investigated the role accomplished by polydatin, a natural antioxidative compound, in promoting osteogenic differentiation alone or after radiation therapy on osteosarcoma cells. Read More

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The Influence of Corticosteroids, Immunosuppressants and Biologics on Patients With Inflammatory Bowel Diseases, Psoriasis and Rheumatic Diseases in the Era of COVID-19: A Review of Current Evidence.

Front Immunol 2021 8;12:677957. Epub 2021 Jul 8.

Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.

Patients with inflammatory bowel disease, psoriasis or other rheumatic diseases treated with corticosteroids, immunomodulators and biologics might face additional risk during COVID-19 epidemic due to their immunocompromised status. However, there was still no unanimous opinion on the use of these therapy during COVID-19 epidemic. Current studies suggested that systemic corticosteroids might increase the risk of hospitalization, as well as risks of ventilation, ICU, and death among patients with immune-mediated inflammatory diseases. Read More

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Babao Dan is a robust anti-tumor agent via inhibiting wnt/β-catenin activation and cancer cell stemness.

J Ethnopharmacol 2021 Jul 28;280:114449. Epub 2021 Jul 28.

Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China. Electronic address:

Ethnopharmacological Relevance: Traditional Chinese Medicine (TCM) is being increasingly used worldwide due to its diverse efficacy and relatively low side effects. Babao Dan (BBD) is a well-known TCM formula that is currently used for the effective treatment of various cancers, however its underlying molecular mechanism remains unknown.

Aim Of The Study: Tumor growth and tumor recurrence are characterized by two distinct populations of cells, namely the well-differentiated cancer cells composing the majority of tumor bulk, and cancer stem cells (CSCs) involved in tumor relapse, which are both strongly associated with excessive activation of Wnt/β-catenin signaling. Read More

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Alkaloid derivative ION-31a inhibits breast cancer metastasis and angiogenesis by targeting HSP90α.

Bioorg Chem 2021 Jul 22;115:105201. Epub 2021 Jul 22.

School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China; Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China. Electronic address:

Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. Read More

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Pirfenidone modulates macrophage polarization and ameliorates radiation-induced lung fibrosis by inhibiting the TGF-β1/Smad3 pathway.

J Cell Mol Med 2021 Jul 29. Epub 2021 Jul 29.

Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, China.

Radiation-induced lung injury (RILI) mainly contributes to the complications of thoracic radiotherapy. RILI can be divided into radiation pneumonia (RP) and radiation-induced lung fibrosis (RILF). Once RILF occurs, patients will eventually develop irreversible respiratory failure; thus, a new treatment strategy to prevent RILI is urgently needed. Read More

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"Turn-on" unsymmetrical azine based fluorophore for the selective detection of diethylchlorophosphate via photoinduced electron transfer to intramolecular charge transfer pathway.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 21;263:120206. Epub 2021 Jul 21.

School of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, India; Faculty Recharge Programme, University Grants Commission, New Delhi, India. Electronic address:

The detection of chemical warfare agents (CWAs) in a highly selective, sensitive and speedy manner is essential for public safety in the case of terrorist attacks and achieving this is a challenging task. This study involves in developing a new unsymmetrical azine based fluorophore 4-((E)-(((E)-2-methoxybenzylidene)hydrazono)methyl)benzonitrile[A1] which shows high selectivity and sensitivity to the nerve agent mimic molecule, diethylchlorophosphate (DCP) through fluorescence switch on mechanism. In a fascinating manner, DCP sensing by A1 operates via solvent dependent optical output mechanisms. Read More

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Diosgenin exerts anti-tumor effects through inactivation of cAMP/PKA/CREB signaling pathway in colorectal cancer.

Eur J Pharmacol 2021 Jul 27;908:174370. Epub 2021 Jul 27.

Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China. Electronic address:

Colorectal cancer (CRC) is the most fatal gastrointestinal tumor and it is urge to explore powerful drugs for the treatment. Diosgenin (DSG) as a new steroidal had been reported exerts anti-tumor activity in multiple cancers, including CRC. However, the potential mechanism of DSG suppresses CRC remains further to be revealed. Read More

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A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model.

Biomed Pharmacother 2021 Jul 10;141:111877. Epub 2021 Jul 10.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, PR China. Electronic address:

Leukemia is responsible for a reason of death, globally. Even though there are several treatment regimens available in the clinics against this disease, a perfect chemotherapeutic agent for the same is still under investigation. Natural plant-derived secondary metabolites are used in clinics to treat leukemia for better benefits with reduced side-effects. Read More

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Biochanin A Alleviates Cerebral Ischemia/Reperfusion Injury by Suppressing Endoplasmic Reticulum Stress-Induced Apoptosis and p38MAPK Signaling Pathway and .

Front Endocrinol (Lausanne) 2021 12;12:646720. Epub 2021 Jul 12.

Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China.

We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. Read More

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Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap).

Sci Rep 2021 Jul 28;11(1):15313. Epub 2021 Jul 28.

Department of Anatomy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Saxony, Germany.

Ischemic retinal dystrophies are leading causes of acquired vision loss. Although the dysregulated expression of the hypoxia-responsive VEGF-A is a major driver of ischemic retinopathies, implication of additional VEGF-family members in their pathogenesis has led to the development of multivalent anti-angiogenic tools. Designed as a decoy receptor for all ligands of VEGFR1 and VEGFR2, Aflibercept is a potent anti-angiogenic agent. Read More

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Sophocarpine Attenuates Cognitive Impairment and Promotes Neurogenesis in a Mouse Model of Alzheimer's Disease.

Neuroimmunomodulation 2021 Jul 28:1-12. Epub 2021 Jul 28.

Neurobiology Laboratory, Institute of Basic Medicine, Hebei Medical University, Shijiazhang, China.

Introduction: Alzheimer's disease (AD), which is characterized by abnormal deposition of amyloid-β (Aβ) plaques and impaired neurogenesis and cognition, still lacks an optimally effective therapeutic agent for its management, and mounting evidence has shown that inflammatory processes are implicated in AD. Sophocarpine has been reported to exert inflammation-regulating effects in various diseases. However, whether sophocarpine can exert anti-neuroinflammatory and neuroprotective effects in AD remains unclear. Read More

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Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N'-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis.

Phytomedicine 2021 Jun 6;91:153619. Epub 2021 Jun 6.

Department of Pharmacy, Chinese PLA General Hospital, Beijing, China. Electronic address:

Backgrounds: Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches.

Methods: Therapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. Read More

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BCL2 inhibitors and MCL1 inhibitors for hematological malignancies.

Blood 2021 Jul 28. Epub 2021 Jul 28.

University of Melbourne, Australia.

BCL2 and MCL1 are commonly expressed pro-survival (anti-apoptotic) proteins in hematological cancers and play important roles in their biology either through dysregulation or by virtue of intrinsic importance to the cell-of-origin of the malignancy. A new class of small molecule anti-cancer drugs, BH3-mimetics, now enable specific targeting of these proteins in patients. BH3-mimetics act by inhibiting the pro-survival BCL2 proteins to enable the activation of BAX and BAK, apoptosis effectors which permeabilize the outer mitochondrial membrane, triggering apoptosis directly in many cells and sensitizing others to cell death when combined with other anti-neoplastic drugs. Read More

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The fish pathogen LFI1238 can degrade and metabolize chitin despite major gene loss in the chitinolytic pathway.

Appl Environ Microbiol 2021 Jul 28:AEM0052921. Epub 2021 Jul 28.

Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences (NMBU), Ås, Norway.

The fish pathogen LFI1238 is thought to be incapable of utilizing chitin as a nutrient source since approximately half of the genes representing the chitinolytic pathway are disrupted by insertion sequences. In the present study, we combined a broad set of analytical methods to investigate this hypothesis. Cultivation studies revealed that grew efficiently on -acetylglucosamine (GlcNAc) and chitobiose ((GlcNAc)), the primary soluble products resulting from enzymatic chitin hydrolysis. Read More

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Blocking MMP-12-modulated epithelial-mesenchymal transition by repurposing penfluridol restrains lung adenocarcinoma metastasis via uPA/uPAR/TGF-β/Akt pathway.

Cell Oncol (Dordr) 2021 Jul 28. Epub 2021 Jul 28.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, 11031, Taipei, Taiwan.

Purpose: Metastasis of lung adenocarcinoma (LADC) is a crucial factor determining patient survival. Repurposing of the antipsychotic agent penfluridol has been found to be effective in the inhibition of growth of various cancers. As yet, however, the anti-metastatic effect of penfluridol on LADC has rarely been investigated. Read More

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Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis.

Oncotarget 2021 Jul 20;12(15):1470-1489. Epub 2021 Jul 20.

Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Objective: Aberrations in the PI3K/AKT/mTOR survival pathway in many cancers are the most common genomic abnormalities. The phytochemical and bioactive agent sulforaphane (SFN) has nutrigenomic potential in activating the expression of several cellular protective genes via the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is primarily related to mechanisms of endogenous cellular defense and survival. Read More

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Protopine triggers apoptosis via the intrinsic pathway and regulation of ROS/PI3K/Akt signalling pathway in liver carcinoma.

Cancer Cell Int 2021 Jul 27;21(1):396. Epub 2021 Jul 27.

Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, Zhejiang, China.

Background: Protopine is an isoquinoline alkaloid that possesses various biological activities including the anti-tumour activity. However, the effects of protopine on liver carcinoma cells are still elusive. The aim of this study is to examine the effects of protopine on liver carcinoma cells both in vitro and in vivo. Read More

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A novel mechanism of lung cancer inhibition by methionine enkephalin through remodeling the immune status of the tumor microenvironment.

Int Immunopharmacol 2021 Jul 24;99:107999. Epub 2021 Jul 24.

Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang 110122, China. Electronic address:

This study examined the antitumor effect of methionine enkephalin (MENK) against lung cancer in vivo and in vitro and explored the underlying mechanisms. Changes in the immune status of the tumor microenvironment (TME) in response to MENK administration were examined in mice. MENK significantly inhibited the proliferation of lung cancer cells in vivo and in vitro by regulating the Wnt/β-catenin pathway and causing cell cycle arrest at the G0/G1 phase. Read More

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