180,085 results match your criteria mechanism signaling


Perturbation of miR-146b and relevant inflammatory elements in esophageal carcinoma patients supports an immune downregulatory mechanism.

Pathol Res Pract 2021 Jul 20;225:153560. Epub 2021 Jul 20.

Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Background: Esophageal Cancer is known as one of the deadliest cancers worldwide with the squamous cell carcinoma (ESCC) being the predominant subtype. There is a growing body of evidence linking the dysregulated microRNA (miRNA) pathway of immune cells to the progression of several tumors. In a previous study, we investigated molecular alterations pertaining to miR-146a and some components of NF-kB signaling pathway and proposed a possible immune downregulatory mechanism in peripheral blood mononuclear cells (PBMCs) of ESCC patients. Read More

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Interplay between Sae2 and Rif2 in the regulation of Mre11-Rad50 activities at DNA ends.

Curr Opin Genet Dev 2021 Jul 23;71:72-77. Epub 2021 Jul 23.

Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano, 20126, Italy. Electronic address:

DNA double-strand breaks (DSBs) can be repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR). HR is initiated by nucleolytic degradation of the DSB ends in a process termed resection. The Mre11-Rad50-Xrs2/NBS1 (MRX/N) complex is a multifunctional enzyme that, aided by the Sae2/CtIP protein, promotes DSB resection and maintains the DSB ends tethered to each other to facilitate their re-ligation. Read More

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Particle-bound PAHs induced glucose metabolism disorders through HIF-1 pathway.

Sci Total Environ 2021 Jul 20;797:149132. Epub 2021 Jul 20.

Key Laboratory of the Three Gorges Reservoir Eco-environment, Ministry of Education, Chongqing University, 174 Shazheng Road Shapingba, 400045 Chongqing, China. Electronic address:

Vehicle exhaust, as one of the most important compositions of air pollution, induced various adverse health effects, especially diabetes, on human beings. Even though monitoring and epidemiological data indicates that particle-bound polycyclic aromatic hydrocarbons (PAHs) is an inducing factor of diabetes, the specific causative mechanisms are still unclear. In the current study, the concentration of particulate matters (PMs, including PM, PM and PM) and PAHs was investigated at rush hour of weekday in three urban underground parking garages (UPGs). Read More

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Regulatory role of methionine enkephalin in myeloid-derived suppressor cells and macrophages in human cutaneous squamous cell carcinoma.

Int Immunopharmacol 2021 Jul 23;99:107996. Epub 2021 Jul 23.

Department of Gynecology, The Fourth Affiliated Hospital of China Medical University, 4 Chongshandong Road, Huanggu District, Shenyang, Liaoning 110004, China. Electronic address:

The antitumor effects of methionine enkephalin (MENK), also known as opioid growth factor (OGF), including its inhibitory effects on cutaneous squamous cell carcinoma (CSCC), have been established. In this study, we determined the precise mechanism by which MENK suppresses CSCC cell growth. In particular, MENK induced G0/G1 cell cycle arrest and promoted apoptosis in CSCC cells via the Bcl-2/Bax/Caspase-3 signaling pathway. Read More

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Zhuanggu Zhitong Capsule alleviates osteosarcopenia in rats by up-regulating PI3K/Akt/Bcl2 signaling pathway.

Biomed Pharmacother 2021 Jul 23;142:111939. Epub 2021 Jul 23.

The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510375, China. Electronic address:

Background And Aims: Osteosarcopenia (OS), characterized by the coexistence of osteoporosis (OP) and sarcopenia (SP), is associated with high morbidity and mortality in the elderly. Nevertheless, its pathogenesis and treatment remain unclear. The aim of this study was to investigate the effect and mechanism of Zhuanggu Zhitong Capsule (ZGZT) in OS rats. Read More

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Protective role of microRNA-31 in acetaminophen-induced liver injury: a negative regulator of c-Jun N-terminal kinase (JNK) signaling pathway.

Cell Mol Gastroenterol Hepatol 2021 Jul 23. Epub 2021 Jul 23.

Department of Liver Surgery and Liver Transplantation Center, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.

Background & Aims: Sustained JNK activation plays a major role in drug-induced liver injury (DILI). Stress-responsive microRNA-31 (miR-31) has been implicated in regulating different cellular damage, and JNK activation could induce miR-31 expression. However, the regulatory role of miR-31 in DILI has not been previously studied. Read More

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Bioassay-guided study of the anti-inflammatory effect of Anoectochilus burmannicus ethanolic extract in RAW 264.7 cells.

J Ethnopharmacol 2021 Jul 23:114452. Epub 2021 Jul 23.

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai, 50200, Thailand. Electronic address:

Ethnopharmacological Relevance: Anoectochilus species is a small terrestrial orchid found in tropical and subtropical rain forest. These orchids are traditionally used extensively in China, Taiwan, and Vietnam due to their medicinal properties and therapeutic benefits. They are employed for treatment in different systems, such as stomach disorders, chest pain, arthritis, tumor, piles, boils, menstrual disorders, and inflammation. Read More

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GSK-3β inhibitor TWS119 alleviates hypoxic-ischemic brain damage via a crosstalk with Wnt and Notch signaling pathways in neonatal rats.

Brain Res 2021 Jul 24:147588. Epub 2021 Jul 24.

Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050, China. Electronic address:

Preterm infant brain injury is a leading cause of morbidity and disability in survivors of preterm infants. Unfortunately, the effective treatment remains absent. Recent evidence suggests that GSK-3β inhibitor TWS119 has a neuroprotectiverole in adult brain injury by activation of Wnt/β-catenin signaling pathway. Read More

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Estrogen protects against acidosis-mediated articular chondrocyte injury by promoting ASIC1a protein degradation.

Eur J Pharmacol 2021 Jul 23:174381. Epub 2021 Jul 23.

The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, 230032, China. Electronic address:

Epidemiological data suggest that the incidence of rheumatoid arthritis (RA) increases in postmenopausal women, which may be related to estrogen deficiency. Tissue acidosis is a common symptom of RA. Acid-sensitive ion channel 1a (ASIC1a), a member of the extracellular H-activated cation channel family, could be activated by changes in extracellular pH and plays a crucial role in the pathogenesis of RA. Read More

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DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction.

PLoS Pathog 2021 Jul 26;17(7):e1008603. Epub 2021 Jul 26.

Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.

Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients and highly associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure, and disseminated intravascular coagulation as the disease progresses of DHF/DSS patients, which can lead to the death of patients. Read More

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Fasting increases 18:2-containing phosphatidylcholines to complement the decrease in 22:6-containing phosphatidylcholines in mouse skeletal muscle.

PLoS One 2021 26;16(7):e0255178. Epub 2021 Jul 26.

Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.

Fasting stimulates catabolic reactions in skeletal muscle to survive nutrient deprivation. Cellular phospholipids have large structural diversity due to various polar-heads and acyl-chains that affect many cellular functions. Skeletal muscle phospholipid profiles have been suggested to be associated with muscle adaptations to nutritional and environmental status. Read More

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pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1β and type I IFN production.

PLoS Pathog 2021 Jul 26;17(7):e1009733. Epub 2021 Jul 26.

Division of Fundamental Immunology, National African Swine Fever Para-reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

Inflammatory factors and type I interferons (IFNs) are key components of host antiviral innate immune responses, which can be released from the pathogen-infected macrophages. African swine fever virus (ASFV) has developed various strategies to evade host antiviral innate immune responses, including alteration of inflammatory responses and IFNs production. However, the molecular mechanism underlying inhibition of inflammatory responses and IFNs production by ASFV-encoded proteins has not been fully understood. Read More

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Dimeric allostery mechanism of the plant circadian clock photoreceptor ZEITLUPE.

PLoS Comput Biol 2021 Jul 26;17(7):e1009168. Epub 2021 Jul 26.

Department of Chemistry, Center for Research Computing, Center for Drug Discovery, Design, and Delivery (CD4), Southern Methodist University, Dallas, Texas, United States of America.

In Arabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. Here, we delineate the allosteric mechanism of ZTL via an integrated computational approach that employs atomistic simulations of wild type and allosteric variants of ZTL in the functional dark and light states, together with Markov state and supervised machine learning classification models. Read More

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LPS-induced autophagy in human dental pulp cells is associated with p38.

J Mol Histol 2021 Jul 26. Epub 2021 Jul 26.

Department of Operative Dentistry and Endodontics, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Ling yuan Road West, Guangzhou, 510055, China.

Lipopolysaccharides (LPS), which are components of the cell wall of Gram-negative bacteria, are among the important factors that induce inflammation, including pulpitis. Autophagy in human dental pulp cells (hDPCs) acts as a protective mechanism that promotes cell survival under adverse conditions through different signaling pathways. In this study, we examined whether LPS increases autophagy in hDPCs and investigated the role of mitogen-activated protein kinases signaling and nuclear factor κB (NF-κB) in this process. Read More

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Sinensetin Attenuates Amyloid Beta-Induced Oxidative Stress, Inflammation, and Apoptosis in SH-SY5Y Cells Through the TLR4/NF-κB Signaling Pathway.

Neurochem Res 2021 Jul 26. Epub 2021 Jul 26.

Department of Neurology, Kangda College of Nanjing Medical University Affiliated Lianshui County People's Hospital, 6 Hongri Avenue East, Lianshui County, Huai'an, 223400, Jiangsu, People's Republic of China.

Sinensetin (SIN) is an important active compound that exists widely in citrus plants, and has been reported to exhibit various pharmacological properties, including anti-oxidative, anti-inflammatory, and anti-tumor. This study was designed to examine whether SIN can protect against amyloid beta (Aβ)-induced neurotoxicity and to elucidate the underlying mechanism. Our results showed that pretreatment with SIN for 1 h, followed by co-treatment with Aβ plus SIN for 24 h, attenuated Aβ-induced cell viability reduction, oxidative stress, inflammation, and apoptosis in a dose-dependent manner. Read More

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HOXC13 promotes cervical cancer proliferation, invasion and Warburg effect through β-catenin/c-Myc signaling pathway.

J Bioenerg Biomembr 2021 Jul 26. Epub 2021 Jul 26.

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), NO.1, banshangdong Road, Gongshu District, 310000, Hangzhou, China.

Cervical cancer (CC) is one of the most common malignancy and is the second leading cause of death in gynecologic malignancies worldwide. The homeobox transcription factor homeobox C13 (HOXC13) has been demonstrated to play crucial roles in various cancers. However, its function in CC remains to be addressed. Read More

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Targeting CDK4 overcomes EMT-mediated tumor heterogeneity and therapeutic resistance in KRAS mutant lung cancer.

JCI Insight 2021 Jul 22. Epub 2021 Jul 22.

Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America.

Lack of sustained response to therapeutic agents in patients with KRAS mutant lung cancer poses a major challenge and arises partly due to intratumor heterogeneity that defines phenotypically distinct tumor subpopulations. To attain better therapeutic outcomes it is important to understand the differential therapeutic sensitivities of tumor cell subsets. Epithelial-to-mesenchymal transition (EMT) is a biologic phenomenon that can alter the state of cells along a phenotypic spectrum and cause transcriptional rewiring to produce distinct tumor cell subpopulations. Read More

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Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment.

Elife 2021 Jul 26;10. Epub 2021 Jul 26.

University of Michigan School of Dentistry, Ann Arbor, United States.

Chondrocytes in the resting zone of the postnatal growth plate are characterized by slow cell cycle progression, and encompass a population of parathyroid hormone-related protein (PTHrP)-expressing skeletal stem cells that contribute to the formation of columnar chondrocytes. However, how these chondrocytes are maintained in the resting zone remains undefined. We undertook a genetic pulse-chase approach to isolate slow cycling, label-retaining chondrocytes (LRCs) using a chondrocyte-specific doxycycline-controllable Tet-Off system regulating expression of histone 2B-linked GFP. Read More

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HNRNPU-AS1 regulates cell proliferation and apoptosis via miR-205-5p/AXIN2 axis and Wnt/β-catenin signaling pathway in cervical cancer.

Mol Cell Biol 2021 Jul 26:MCB0011521. Epub 2021 Jul 26.

Department of Gynaecology, the Affiliated Hospital of Qingdao University, Qingdao 266102, China.

Long non-coding RNAs (lncRNAs) have key functions in modulating cervical cancer (CC) genesis and progression. This work focused on exploring lncRNA HNRNPU-AS1's function in CC and the underlying mechanism. HNRNPU-AS1, AXIN2 and miR-205-5p levels in CC cases were measured through RT-qPCR. Read More

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Ginsenoside Rg5 Improves Insulin Resistance and Mitochondrial Biogenesis of Liver via Regulation of the Sirt1/PGC-1α Signaling Pathway in db/db Mice.

J Agric Food Chem 2021 Jul 26. Epub 2021 Jul 26.

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an 710069, China.

Type 2 diabetes mellitus (T2DM) is a common metabolic syndrome that decreases insulin sensitivity and mitochondrial biogenesis in the liver. Our previous study demonstrated that ginsenoside Rg5 (Rg5) could attenuate renal injury in diabetic mice but its underlying mechanism in mitochondrial biogenesis and insulin sensitivity remains poorly understood. In this study, we found that Rg5 intervention significantly inhibited blood glucose increases in db/db mice, improved liver function damage and hepatocyte apoptosis, and activated the IRS-1/phosphatidylinositol 3-kinase/AKT insulin metabolism signaling pathway. Read More

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Polypeptide LTX-315 reverses the cisplatin chemoresistance of ovarian cancer cells via regulating Beclin-1/PI3K/mTOR signaling pathway.

J Biochem Mol Toxicol 2021 Jul 26:e22853. Epub 2021 Jul 26.

Department of Obstetrics and Gynecology, The First Clinical Medical College of Harbin Medical University, Harbin, China.

Objective: Polypeptide LTX-315 induces immunogenic cell death, thus having the potential to improve the effect of anticancer treatment. However, the function of LTX-315 in reversing chemoresistance in ovarian cancer (OC) still remains elusive. Our study aims to decipher the effect of LTX-315 on reversing the chemoresistance of OC cells and explore its mechanism. Read More

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Asymmetric left-right hippocampal glutamatergic modulation of cognitive control in ApoE-isoform subjects is unrelated to neuroinflammation.

Eur J Neurosci 2021 Jul 26. Epub 2021 Jul 26.

Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong.

The glutamatergic cycle is essential in modulating memory processing by the hippocampal circuitry. Our combined H-MRS and task-based fMRI study (using face-name paired-associates encoding and retrieval task) of a cognitively-normal cohort of 67 healthy adults (18 ApoE4 carriers and 49 non-ApoE4 carriers) found altered patterns of relationships between glutamatergic-modulated synaptic signaling and neuronal activity or functional hyperaemia in the ApoE4 isoforms. Our study highlighted the asymmetric left-right hippocampal glutamatergic system in modulating neuronal activities in ApoE4 carriers versus non-carriers. Read More

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Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling in the facial mesenchyme.

Development 2021 07 13;148(14). Epub 2021 Jul 13.

Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) is crucial for mammalian craniofacial development, although the mechanisms by which the activity of downstream intracellular effectors is regulated to mediate gene expression changes have not been defined. We find that the RNA-binding protein Srsf3 is phosphorylated at Akt consensus sites downstream of PI3K-mediated PDGFRα signaling in mouse palatal mesenchyme cells, leading to its nuclear translocation. We further demonstrate that ablation of Srsf3 in the mouse neural crest lineage leads to facial clefting due to defective cranial neural crest cell proliferation and survival. Read More

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[Gene expression profiles of myopic mouse scleral fibroblasts: a bioinformatics analysis based on single-cell RNA sequencing].

Authors:
J Yu Y Mo

Nan Fang Yi Ke Da Xue Xue Bao 2021 Jul;41(7):1087-1092

Department of Ophthalmology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

Objective: To investigate the changes in gene expression profiles of mouse scleral fibroblasts after myopia using single-cell RNA sequencing technology and explore the mechanism of dysfunction of the scleral fibroblasts in myopia.

Methods: Normal healthy C57BL/6J mice were randomly divided into negative control group and myopia model group (=6), and in the latter group, form deprivation myopia was induced in the right eye using translucent goggles. Single cell capture was performed in the right eye to obtain the scleral fibroblasts for RNA sequencing. Read More

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[Exendin-4 promotes autophagy to relieve lipid deposition in a NAFLD cell model by activating AKT/mTOR signaling pathway].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Jul;41(7):1073-1078

Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.

Objective: To investigate the effect of exendin-4 on lipid deposition in hepatocytes and explore its possible mechanism for treatment of nonalcoholic fatty liver disease (NAFLD).

Methods: Human normal hepatocyte line LO2 and hepatoma cell line HepG2 were treated with palmitic acid (PA) to mimic hepatocyte steatosis or with combined treatments with PA+exendin-4 or PA+exendin-4+3BDO. Lipid deposition and proliferation of the two cell lines following treatment with PA or PA+exendin-4 were detected using Oil Red O staining and CCK8 assay, and the expression of p-mTOR, m-TOR, p-AKT, AKT and autophagy-related proteins LC3-Ⅰ/Ⅱ and p62 were detected with Western blotting; the expression of GLP-1R was detected with both Western blotting and immunofluorescence assay. Read More

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[Balectin-3 affects the stability of vulnerable coronary atherosclerosis plaques by targeted modulation of lncARSR].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Jul;41(7):1067-1072

Sanshui Hospital Affiliated to Guangdong Medical University, Foshan 528100, China.

Objective: To investigate the mechanism by which galectin-3 (Gal-3) affects the stability of vulnerable coronary atherosclerosis plaques through long non-coding RNA ARSR (lncARSR).

Method: Male BALB/c mice were randomly divided into normal diet group, high-fat diet group, high-fat diet+lncARSR inhibitor group (=20). The high-fat diet contained 15% fat and 0. Read More

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Quercetin protects oral mucosal keratinocytes against lipopolysaccharide-induced inflammatory toxicity by suppressing the AKT/AMPK/mTOR pathway.

Immunopharmacol Immunotoxicol 2021 Jul 26:1-8. Epub 2021 Jul 26.

Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.

Background: Cytokines can induce a chronic inflammatory response in the periodontium, leading to periodontitis. Quercetin, a naturally occuring flavonoid, has been shown to inhibit periodontitis, but how it works is poorly understood. In this study, we assessed the impact of quercetin on lipopolysaccharide (LPS)-induced inflammatory damage in oral mucosal keratinocytes (hOMK107) and explored its underlying mechanism. Read More

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Proteasomal adaptations to FDA-approved proteasome inhibitors: a potential mechanism for drug resistance?

Authors:
Kyung Bo Kim

Cancer Drug Resist 2021 30;4:634-645. Epub 2021 May 30.

Department of Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.

With proteasome inhibitors (PIs) becoming clinically available since 2003, outcomes for patients with multiple myeloma (MM) have dramatically changed, improving quality of life and survival. Despite the impressive treatment success, however, almost all MM patients who initially respond to these PIs eventually develop resistance. Furthermore, a portion of MM patients is inherently unresponsive to the PIs. Read More

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Mechanisms of organophosphate neurotoxicity.

Curr Opin Toxicol 2021 Jun 30;26:49-60. Epub 2021 Apr 30.

Department of Molecular Sciences, University of California, Davis School of Veterinary Medicine, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA.

The canonical mechanism of organophosphate (OP) neurotoxicity is the inhibition of acetylcholinesterase (AChE). However, multiple lines of evidence suggest that mechanisms in addition to or other than AChE inhibition contribute to the neurotoxic effects associated with acute and chronic OP exposures. Characterizing the role(s) of AChE inhibition versus noncholinergic mechanisms in OP neurotoxicity remains an active area of research with significant diagnostic and therapeutic implications. Read More

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Acacetin Protects Myocardial Cells against Hypoxia-Reoxygenation Injury through Activation of Autophagy.

J Immunol Res 2021 29;2021:9979843. Epub 2021 Jun 29.

Xinjiang Institute of Materia Medica, Uygur, Xinjiang Province 830004, China.

Ischemic heart disease is a leading cause of mortality and morbidity worldwide. We previously demonstrated that acacetin protects against myocardial ischemia reperfusion injury in rats, although the underlying mechanism remains to be elucidated. In the present study, we investigated the effects of acacetin on autophagy during hypoxia/reoxygenation (H/R) injury by exposing H9c2 myocardial cells to H/R with or without acacetin pretreatment during hypoxia. Read More

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