-
1
المؤلفون: Davide Schiroli, Roberta Chicchi, Tommaso Fasano, Giuseppe Molinari, Stefano Pulcini, Thelma A. Pertinhez, C Marraccini, Rino Biguzzi, Roberto Baricchi, Erminia Di Bartolomeo, Lucia Merolle, Eleonora Quartieri, Tiziana De Luca
المصدر: Biomolecules, Vol 11, Iss 1638, p 1638 (2021)
Biomolecules
Volume 11
Issue 11مصطلحات موضوعية: Adult, Blood Platelets, Male, medicine.medical_specialty, Blood transfusion, Erythrocytes, medicine.medical_treatment, Iron, blood transfusion, Biochemistry, Hemolysis, Microbiology, Article, Electrolytes, Quality of life, Internal medicine, medicine, Leukocytes, Humans, iron overload, Molecular Biology, metabolites, L-Lactate Dehydrogenase, business.industry, beta-Thalassemia, packed red blood cells, Blood Proteins, QR1-502, Whole blood units, β-thalassemia, Metabolome, Cytokines, Transfusion therapy, Packed red blood cells, business, Erythrocyte Transfusion, β thalassemia major
الوصف: β-thalassemia major (βTM) patients require frequent blood transfusions, with consequences that span from allogenic reactions to iron overload. To minimize these effects, βTM patients periodically receive leucodepleted packed red blood cells (P-RBCs) stored for maximum 14 days. The aim of this study was to compare two alternative routine procedures to prepare the optimal P-RBCs product, in order to identify differences in their content that may somehow affect patients’ health and quality of life (QoL). In method 1, blood was leucodepleted and then separated to obtain P-RBCs, while in method 2 blood was separated and leucodepleted after removal of plasma and buffycoat. Forty blood donors were enrolled in two independent centers
couples of phenotypically matched whole blood units were pooled, divided in two identical bags and processed in parallel following the two methods. Biochemical properties, electrolytes and metabolic composition were tested after 2, 7 and 14 days of storage. Units prepared with both methods were confirmed to have all the requirements necessary for βTM transfusion therapy. Nevertheless, RBCs count and Hb content were found to be higher in method-1, while P-RBCs obtained with method 2 contained less K+, iron and storage lesions markers. Based on these results, both methods should be tested in a clinical perspective study to determine a possible reduction of transfusion-related complications, improving the QoL of βTM patients, which often need transfusions for the entire lifespan.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a347f2562f3dfd614ab46b8bd93fef1fTest
https://www.mdpi.com/2218-273X/11/11/1638Test -
2
المؤلفون: Takuya Mori, Yi Luo, Rina Fujiwara-Tani, Shiori Mori, Isao Kawahara, Kiyomu Fujii, Tadaaki Kirita, Shingo Kishi, Hiroki Kuniyasu, Kazuhiko Yamamoto, Chie Nakashima, Hitoshi Ohmori, Kei Goto, Takamitsu Sasaki
المصدر: International Journal of Molecular Sciences, Vol 21, Iss 7149, p 7149 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 19مصطلحات موضوعية: Male, Oxidative Phosphorylation, lcsh:Chemistry, Malate Dehydrogenase, ME1, Glycolysis, RNA, Small Interfering, lcsh:QH301-705.5, Spectroscopy, Gene knockdown, education.field_of_study, Symporters, Kinase, Chemistry, digestive, oral, and skin physiology, EMT, food and beverages, General Medicine, Hydrogen-Ion Concentration, Middle Aged, Warburg effect, Cell Hypoxia, Computer Science Applications, Gene Expression Regulation, Neoplastic, Lymphatic Metastasis, Carcinoma, Squamous Cell, Disease Progression, Female, Mouth Neoplasms, extracellular pH, Signal Transduction, Monocarboxylic Acid Transporters, musculoskeletal diseases, Epithelial-Mesenchymal Transition, Lactate dehydrogenase A, tumor budding, Article, Catalysis, Inorganic Chemistry, Tumor budding, Cell Line, Tumor, Extracellular, Humans, Physical and Theoretical Chemistry, education, Molecular Biology, Adaptor Proteins, Signal Transducing, Aged, Cell Proliferation, L-Lactate Dehydrogenase, hypoxia, Organic Chemistry, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, YAP-Signaling Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, stomatognathic diseases, lcsh:Biology (General), lcsh:QD1-999, Cancer cell, Cancer research, Transcription Factors
الوصف: Budding at the tumor invasive front has been correlated with the malignant properties of many cancers. Malic enzyme 1 (ME1) promotes the Warburg effect in cancer cells and induces epithelial&ndash
mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Therefore, we investigated the role of ME1 in tumor budding in OSCC. Tumor budding was measured in 96 human OSCCs by immunostaining for an epithelial marker (AE1/AE3), and its expression was compared with that of ME1. A significant correlation was observed between tumor budding and ME1 expression. The correlation increased with the progression of cancer. In human OSCC cells, lactate secretion decreased when lactate fermentation was suppressed by knockdown of ME1 and lactate dehydrogenase A or inhibition of pyruvate dehydrogenase (PDH) kinase. Furthermore, the extracellular pH increased, and the EMT phenotype was suppressed. In contrast, when oxidative phosphorylation was suppressed by PDH knockdown, lactate secretion increased, extracellular pH decreased, and the EMT phenotype was promoted. Induction of chemical hypoxia in OSCC cells by CoCl2 treatment resulted in increased ME1 expression along with HIF1&alpha
expression and promotion of the EMT phenotype. Hypoxic conditions also increased matrix metalloproteinases expression and decreased mitochondrial membrane potential, mitochondrial oxidative stress, and extracellular pH. Furthermore, the hypoxic treatment resulted in the activation of Yes-associated protein (YAP), which was abolished by ME1 knockdown. These findings suggest that cancer cells at the tumor front in hypoxic environments increase their lactate secretion by switching their energy metabolism from oxidative phosphorylation to glycolysis owing to ME1 overexpression, decrease in extracellular pH, and YAP activation. These alterations enhance EMT and the subsequent tumor budding. Tumor budding and ME1 expression are thus considered useful markers of OSCC malignancy, and ME1 is expected to be a relevant target for molecular therapy.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::128e42b93750eb136999872d1627aeb1Test
https://www.mdpi.com/1422-0067/21/19/7149Test -
3
المؤلفون: Blassan P. George, Rahul Chandran, Heidi Abrahamse
المصدر: Molecules, Vol 25, Iss 2900, p 2900 (2020)
Molecules
Volume 25
Issue 12مصطلحات موضوعية: Male, Syzygium, Pharmaceutical Science, Pharmacology, 030226 pharmacology & pharmacy, Analytical Chemistry, chemistry.chemical_compound, Mice, 0302 clinical medicine, Adenosine Triphosphate, Drug Discovery, Edema, pain, Analgesics, Chemistry, Anti-Inflammatory Agents, Non-Steroidal, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, Toxicity, MCF-7 Cells, Plant Bark, Molecular Medicine, Female, medicine.symptom, medicine.drug_class, inflammatory mediators, Analgesic, Inflammation, Hoechst stain, Anti-inflammatory, Article, lcsh:QD241-441, 03 medical and health sciences, lcsh:Organic chemistry, In vivo, Lactate dehydrogenase, medicine, Toxicity Tests, Acute, Animals, Humans, granuloma tissue, Physical and Theoretical Chemistry, Rats, Wistar, Cell Proliferation, Plants, Medicinal, L-Lactate Dehydrogenase, Plant Extracts, Methanol, Organic Chemistry, lactate dehydrogenase, Antineoplastic Agents, Phytogenic, Carrageenan
الوصف: Cancer, pain and inflammation have long been a cause for concern amongst patients, clinicians and research scientists. There is an alarming increase in the demand for medicines suppressing these disease conditions. The present study investigates the role of Syzygium mundagam bark methanol (SMBM) extract against MCF-7 breast cancer cells, pain and inflammation. The MCF-7 cells treated with SMBM were analyzed for adenosine triphosphate (ATP), lactate dehydrogenase (LDH) levels, changes in cell morphology and nuclear damage. Hot plate, acetic acid and formalin-induced pain models were followed to determine the analgesic activity. Anti-inflammatory activity was studied using carrageenan, egg albumin and cotton pellet induced rat models. Microscopic images of cells in SMBM treated groups showed prominent cell shrinkage and nuclear damage. Hoechst stain results supported the cell death morphology. The decline in ATP (47.96%) and increased LDH (40.96%) content indicated SMBM induced toxicity in MCF-7 cells. In the in vivo study, a higher dose (200 mg/kg) of the extract was found to be effective in reducing pain and inflammation. The results are promising and the action of the extract on MCF-7 cells, pain and inflammation models indicate the potential of drugs of natural origin to improve current therapies.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::989c72e0c8876a1cd6d7f8b4a9574a30Test
https://www.mdpi.com/1420-3049/25/12/2900Test -
4
المصدر: International Journal of Environmental Research and Public Health; Volume 19; Issue 5; Pages: 3059
مصطلحات موضوعية: Adult, Male, Adolescent, L-Lactate Dehydrogenase, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Alanine Transaminase, Bilirubin, Young Adult, Athletes, Reference Values, Potassium, Humans, Female, Aspartate Aminotransferases, biochemistry, hematology, clinical laboratory, exercise, athletes, Creatine Kinase
الوصف: The purpose of this study was to show how continuous exercise affects the basal values of biochemical and hematological parameters in elite athletes. A total of 14,010 samples (male = 8452 and female = 5558 (March 2011–March 2020)) from 3588 elite athletes (male = 2258 and female = 1330, mean age 24.9 ± 6.9 vs. 24.1 ± 5.5 years, respectively) from 32 sport modalities, were studied over 9 years to check the variation of basal biochemical and hematological parameter values. There were differences seen in the basal values of creatine kinase (CK), urea, creatinine, aspartate transaminase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), potassium, total bilirubin, and eosinophil percentage compared to reference population data. However, other analytes showed narrow ranges of variation like glucose, total protein, albumin, sodium, hemoglobin, mean cell volume (MCV), and platelet count. Exercise produces changes in biochemical and hematological basal values of athletes compared to the general population, with the greatest variation in CK, but AST, ALT, LDH, potassium, and total bilirubin (TBil) show high values in serum, only with a wider distribution of values. The data here reflects the effect of exercise on biochemical and hematological parameter baseline ranges in elite athletes. As clinical laboratories use reference intervals to validate clinical reports, these “pseudo” reference intervals should be used when validating laboratory reports.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::713b402a1198e0ff751a16e3857e1d40Test
https://doi.org/10.3390/ijerph19053059Test -
5
المصدر: Nutrients, Vol 13, Iss 1880, p 1880 (2021)
Nutrientsمصطلحات موضوعية: Adult, Male, medicine.medical_specialty, 030209 endocrinology & metabolism, Review, Muscle damage, law.invention, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, muscle damage, 0302 clinical medicine, Randomized controlled trial, law, Lactate dehydrogenase, Internal medicine, Humans, Medicine, TX341-641, Pooled data, branched-chain amino acids, Muscle, Skeletal, muscle soreness, Randomized Controlled Trials as Topic, chemistry.chemical_classification, Nutrition and Dietetics, biology, creatine kinase, Nutrition. Foods and food supply, business.industry, Resistance training, lactate dehydrogenase, inflammatory response, Myalgia, 030229 sport sciences, Amino acid, meta-analysis, resistance exercise, Endocrinology, chemistry, Athletes, Meta-analysis, Dietary Supplements, biology.protein, Creatine kinase, business, Amino Acids, Branched-Chain, Food Science
الوصف: Previous studies have reported the positive effects of branched-chain amino acids (BCAAs) supplementation on lowering plasma markers of muscle damage and subjective soreness after resistance exercise. However, a variety of factors can potentially moderate its efficacy. This meta-analysis aimed to summarize the evidence regarding the effect of BCAAs supplementation on plasma muscle damage markers and soreness after resistance exercise in only trained males, by considering the plasma lactate dehydrogenase (LDH) and creatine kinase (CK). Randomized controlled trials were identified through a computerized literature search for the period 2010–2020. The pooled data were analyzed with the random-effects model and heterogeneity using I2. Cochrane Collaboration tools was used for the assessment of risk of bias. Nine studies met the inclusion criteria. A positive effect was found for CK at
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e7a4945eaa6f0854e313127a4779909Test
https://doi.org/10.3390/nu13061880Test -
6
المؤلفون: Predeepkumar Narayanappa Shiroorkar, Imran Kazmi, Kumar Shiva Gubbiyappa, Obaid Afzal, Nagaraja Sreeharsha, Fahad A. Al-Abbasi, Abdulmalik Saleh Alfawaz Altamimi
المصدر: Molecules, Vol 25, Iss 5622, p 5622 (2020)
Molecules
Volume 25
Issue 23مصطلحات موضوعية: Male, PTEN, animal diseases, Pharmaceutical Science, Pharmacology, Analytical Chemistry, Protein Carbonylation, Rats, Sprague-Dawley, sepsis, chemistry.chemical_compound, 0302 clinical medicine, Drug Discovery, Tensin, Cecum, 0303 health sciences, biology, medicine.diagnostic_test, Cell Death, TOR Serine-Threonine Kinases, Heart, Glutathione, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, mTOR, Molecular Medicine, puncture, Cardiomyopathies, STAT3 Transcription Factor, Cardiotonic Agents, Punctures, cecum ligation, Article, Sepsis, lcsh:QD241-441, 03 medical and health sciences, Western blot, tangeretin, lcsh:Organic chemistry, Lactate dehydrogenase, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Autophagy, Animals, Physical and Theoretical Chemistry, Protein kinase B, Ligation, PI3K/AKT/mTOR pathway, 030304 developmental biology, business.industry, Myocardium, AKT, Organic Chemistry, PTEN Phosphohydrolase, medicine.disease, Flavones, Disease Models, Animal, chemistry, biology.protein, Tyrosine, Creatine kinase, business, Proto-Oncogene Proteins c-akt
الوصف: Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and puncture (CLP) in male Sprague&ndash
Dawley rats. Abnormal changes were seen in the heart after the sepsis induction. These abnormalities were analyzed based on the cardiac markers, namely Cardiac myosin light chain-1 (cMLC1) and Cardiac troponin I (cTnl), echocardiography, and plasma parameters, like Lactate dehydrogenase (LDH) and Creatinine kinase (CK). Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue. Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA (gene expression) in the cardiac homogenate. Oxidative damage was analyzed using redox marker, reduced glutathione. This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog (PTEN) expression and acting on the AKT/mTOR pathway. The present findings supported that TG is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f83ce38d2ea0a5388fbccdd114955b5Test
https://www.mdpi.com/1420-3049/25/23/5622Test -
7
المؤلفون: Jung Sook Jin, MinJeong Kim, Syng-Ook Lee, Sung-Jin Bae, Ki-Tae Ha, Hee-Jin Choi, Dongryeol Ryu, Jung Ho Han
المصدر: Molecules
Volume 26
Issue 6
Molecules, Vol 26, Iss 1579, p 1579 (2021)مصطلحات موضوعية: Male, Phytochemicals, Administration, Oral, Pharmaceutical Science, AMP-Activated Protein Kinases, Pharmacology, Sanguisorba, Analytical Chemistry, Sanguisorba officinalis L, Mice, 0302 clinical medicine, Sanguisorba officinalis, Drug Discovery, Glycolysis, 0303 health sciences, education.field_of_study, biology, Chemistry, glycolysis, Physical Functional Performance, Medicine, Korean Traditional, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, herbal medicine, Officinalis, Molecular Medicine, medicine.symptom, Myoblasts, Skeletal, Lactate dehydrogenase A, Alpha (ethology), Inflammation, Article, LDHA, Cell Line, lcsh:QD241-441, 03 medical and health sciences, lcsh:Organic chemistry, medicine, Animals, Lactic Acid, Physical and Theoretical Chemistry, education, 030304 developmental biology, Plants, Medicinal, Muscle fatigue, Plant Extracts, Organic Chemistry, physical performance, biology.organism_classification, Enzyme assay, Mice, Inbred C57BL, Exercise Test, Physical Endurance, biology.protein, Lactate Dehydrogenase 5, Phytotherapy
الوصف: Muscle fatigue is induced by an acute or chronic physical performance inability after excessive physical activity often associated with lactate accumulation, the end-product of glycolysis. In this study, the water-extracted roots of Sanguisorba officinalis L., a herbal medicine traditionally used for inflammation and diarrhea, reduced the activities of lactate dehydrogenase A (LDHA) in in vitro enzyme assay myoblast C2C12 cells and murine muscle tissue. Physical performance measured by a treadmill test was improved in the S. officinalis-administrated group. The analysis of mouse serum and tissues showed significant changes in lactate levels. Among the proteins related to energy metabolism-related physical performance, phosphorylated-AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor-coactivator-1 alpha (PGC-1α) levels were enhanced, whereas the amount of LDHA was suppressed. Therefore, S. officinalis might be a candidate for improving physical performance via inhibiting LDHA and glycolysis.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e31725dd12bf86567d40ea446447ca6Test
https://doi.org/10.3390/molecules26061579Test -
8
المؤلفون: Maged E. Mohamed, Nancy S. Younis
المصدر: Molecules, Vol 24, Iss 10, p 1929 (2019)
Molecules
Volume 24
Issue 10مصطلحات موضوعية: Male, Myocardial Infarction, Pharmaceutical Science, Blood Pressure, Pharmacology, Analytical Chemistry, Rats, Sprague-Dawley, chemistry.chemical_compound, Electrocardiography, 0302 clinical medicine, Drug Discovery, Medicine, Myocardial infarction, Receptor, Creatine Kinase, 0303 health sciences, Membrane Glycoproteins, biology, NF-kappa B, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, cardiovascular system, Molecular Medicine, Sesquiterpenes, heat shock protein 60, Creatine, Protective Agents, Article, lcsh:QD241-441, 03 medical and health sciences, lcsh:Organic chemistry, Lactate dehydrogenase, Animals, cardiovascular diseases, Physical and Theoretical Chemistry, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Polycyclic Sesquiterpenes, Biological Products, L-Lactate Dehydrogenase, business.industry, isoproterenol, Organic Chemistry, medicine.disease, MyD88, TLR2, chemistry, toll-like receptors, TRIF, Myeloid Differentiation Factor 88, biology.protein, TLR4, Creatine kinase, β-caryophyllene, business
الوصف: Myocardial infarction (MI) remains one of the major causes of mortality around the world. A possible mechanism involved in myocardial infarction is the engagement of Toll-like receptors (TLRs). This study was intended to discover the prospective cardioprotective actions of &beta
caryophyllene, a natural sesquiterpene, to ameliorate isoproterenol (ISO)-induced myocardial infarction through HSP-60/TLR/MyD88/NF&kappa
B pathway. &beta
Caryophyllene (100 or 200 mg/kg/day orally) was administered for 21 days then MI was induced via ISO (85 mg/kg, subcutaneous) on 20th and 21st days. The results indicated that ISO induced a significant infarcted area associated with several alterations in the electrocardiogram (ECG) and blood pressure (BP) indices and caused an increase in numerous cardiac indicators such as creatine phosphokinase (CPK), creatine kinase-myocardial bound (CK-MB), lactate dehydrogenase (LDH), and cardiac tropinine T (cTnT). In addition, ISO significantly amplified heat shock protein 60 (HSP-60) and other inflammatory markers, such as TNF-&alpha
IL-I&beta
and NF&kappa
B, and affected TLR2 and TLR4 expression and their adaptor proteins
Myeloid differentiation primary response 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-&beta
(TRIF). On the other hand, consumption of &beta
caryophyllene significantly reversed the infarcted size, ECG and BP alterations, ameliorated the ISO elevation in cardiac indicators
it also notably diminished HSP-60, and subsequently TLR2, TLR4, MYD88, and TRIF expression, with a substantial reduction in inflammatory mediator levels. This study revealed the cardioprotective effect of &beta
caryophyllene against MI through inhibiting HSP-60/TLR/MyD88/NF&kappa
B signaling pathways.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::349906ff7bff4ee71a12bae95b7bdbe1Test
https://www.mdpi.com/1420-3049/24/10/1929Test -
9
المؤلفون: Suhail Al-Salam, Priya Yuvaraju, Badreldin H. Ali, Sirin A. Adham, Sumaya Beegam, Abderrahim Nemmar, P. Manoj, Mohammed Al Za'abi, Khalid A. Al Balushi
المصدر: Biomolecules, Vol 10, Iss 762, p 762 (2020)
Biomolecules
Volume 10
Issue 5مصطلحات موضوعية: Male, lcsh:QR1-502, 030204 cardiovascular system & hematology, Tobacco, Waterpipe, medicine.disease_cause, Biochemistry, lcsh:Microbiology, Lipid peroxidation, Mice, chemistry.chemical_compound, 0302 clinical medicine, Gum acacia, Testis, oxidative stress, Testosterone, biology, StAR, NF-kappa B, 030220 oncology & carcinogenesis, Alkaline phosphatase, Lipopolysaccharide binding protein, Gonadal Hormones, medicine.medical_specialty, NF-E2-Related Factor 2, testes, Testicular Diseases, Article, reproductive hormones, 03 medical and health sciences, Gum Arabic, Lactate dehydrogenase, Internal medicine, medicine, Animals, Spermatogenesis, Molecular Biology, Interleukin-6, Tumor Necrosis Factor-alpha, Phosphoproteins, biology.organism_classification, Mice, Inbred C57BL, Endocrinology, chemistry, inflammation, hookah smoke, biology.protein, Tobacco Smoke Pollution, Cotinine, Oxidative stress
الوصف: We investigated some reproductive actions of hookah smoke (HS) exposure (30 min/day, for 30 days) in male mice, and the possible mitigative effect of the prebiotic agent gum acacia (GA) thereon. Control mice were air-exposed (AE). Twenty-four hours after the last exposure, the levels of some plasma reproductive hormones, biochemical markers of inflammation, oxidative and nitrosative stress and testicular histopathology were assessed. The urinary level of cotinine, a major nicotine metabolite, was also measured. HS exposure induced significant decreases in testosterone, estradiol, luteinizing hormone, and androgen binding protein, as well as glutathione reductase activity and levels of nitrite and total nitrite. Plasma inhibin B, alkaline phosphatase, lipopolysaccharide binding protein, uric acid, lactate dehydrogenase, lipid peroxidation, 8-oxo-2&rsquo
deoxyguanosine, and cytochrome C were significantly increased following HS exposure. In testicular homogenate, nuclear factor-&kappa
B (NF-ĸB), nuclear factor erythroid 2&ndash
related factor 2 (Nrf2), interleukin- 6 (IL-6), interleukin-1&beta
(IL-1&beta
), transforming growth factor-&beta
1(TGF- &beta
1), and tumor necrosis factor-&alpha
(TNF- &alpha
) were all significantly elevated, and the steroidogenic acute regulatory protein (StAR) significantly decreased. Histopathologically, there was slight impairment and disorganization of spermatogenesis. Urinary cotinine concentration was elevated significantly in the HS-exposed group compared with the air-exposed group. GA co-administration mitigated the adverse actions of HS measured. In conclusion, daily exposure to HS at the above dose induced adverse actions on the reproductive system of male mice. GA co-administration significantly mitigated these effects by reducing the inflammation, oxidative and nitrosative stress, via a mechanism involving Nrf2, and reduction of StAR expression.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f36152244bd4508c975dce99dd7d7c1Test
https://www.mdpi.com/2218-273X/10/5/762Test -
10
المؤلفون: Benjamin J. Lang, Kuniaki Okamoto, Yuka Okusha, Kisho Ono, Chiharu Sogawa, Masaki Matsumoto, Stuart K. Calderwood, Takanori Eguchi, Manh Tien Tran
المصدر: Cells, Vol 9, Iss 3, p 755 (2020)
Cells
Volume 9
Issue 3مصطلحات موضوعية: Male, Epithelial-Mesenchymal Transition, Chaperonins, Proteome, ectosome, Carcinogenesis, Cell Cycle Proteins, Mice, SCID, Exosome, Article, stressome, Extracellular Vesicles, cell division control 37 (cdc37), Heat Shock Transcription Factors, Stress, Physiological, Cell Line, Tumor, Heat shock protein, Animals, Humans, exosome, Secretion, HSP90 Heat-Shock Proteins, Promoter Regions, Genetic, HSF1, Cell Shape, lcsh:QH301-705.5, cell stress response, Base Sequence, L-Lactate Dehydrogenase, biology, Chemistry, Prostatic Neoplasms, Epithelial Cells, General Medicine, Extracellular vesicle, prostate cancer, LRP1, Hsp90, Cell biology, Gene Expression Regulation, Neoplastic, Prostatic Neoplasms, Castration-Resistant, lcsh:Biology (General), Chaperone (protein), biology.protein, extracellular vesicle, heat shock protein 90 (hsp90), Heat-Shock Response
الوصف: Tumor cells exhibit therapeutic stress resistance-associated secretory phenotype involving extracellular vesicles (EVs) such as oncosomes and heat shock proteins (HSPs). Such a secretory phenotype occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as a soluble form known as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in the release of EV proteins including CD9 and epithelial-to-mesenchymal transition (EMT), a key event in tumor progression. EVs derived from CRPC cells promoted EMT in normal prostate epithelial cells. Some HSP family members and their potential receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein types found by mass spectrometry. The small EVs (30&ndash
200 nm in size) were released even in a non-heated condition from the prostate cancer cells, whereas the EMT-coupled release of EVs (200&ndash
500 nm) and damaged membrane vesicles with associated HSP90&alpha
was increased after heat shock stress (HSS). GAPDH and lactate dehydrogenase, a marker of membrane leakage/damage, were also found in conditioned media upon HSS. During this stress response, the intracellular chaperone CDC37 was transcriptionally induced by heat shock factor 1 (HSF1), which activated the CDC37 core promoter, containing an interspecies conserved heat shock element. In contrast, knockdown of CDC37 decreased EMT-coupled release of CD9-containing vesicles. Triple siRNA targeting CDC37, HSP90&alpha
and HSP90&beta
was required for efficient reduction of this chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, we define &ldquo
stressome&rdquo
as cellular stress-induced all secretion products, including EVs (200&ndash
500 nm), membrane-damaged vesicles and remnants, and extracellular HSP90 and GAPDH. Our data also indicated that CDC37 is crucial for the release of vesicular proteins and tumor progression in prostate cancer.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46064d33050f2b362896af6d7b9bdf93Test
https://www.mdpi.com/2073-4409/9/3/755Test
