المؤلفون: Krista Minéia Wartchow, Letícia Rodrigues, Lucas Zingano Suardi, Barbara Carolina Federhen, Nicholas Guerini Selistre, Carlos-Alberto Gonçalves, Patrícia Sesterheim

المصدر: International Journal of Molecular Sciences, Vol 20, Iss 10, p 2458 (2019)

مصطلحات موضوعية: adipose-derived stromal cells, exendin-4, diabetic rats, insulin-producing cells, p38-MAPK, PI3K/Akt, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Studies using mesenchymal stromal cells (MSCs) as a source of insulin-secreting cells (IPCs) are a promising path in the pursuit for diabetes therapy. Here, we investigate three short-term differentiation protocols in order to generate IPCs from autologous adipose-derived stromal cells (ADSCs) with an expressive insulin-secreting profile in vitro and in vivo, as well as the signaling pathways involved in the chosen differentiation protocols. We extracted and cultured ADSCs and differentiated them into IPCs, using three different protocols with different inductors. Afterwards, the secretory profile was analyzed and IPCs differentiated in exendin-4/activin A medium, which presented the best secretory profile, was implanted in the kidney subcapsular region of diabetic rats. All protocols induced the differentiation, but media supplemented with exendin-4/activin A or resveratrol induced the expression and secretion of insulin more efficiently, and only the exendin-4/activin-A-supplemented medium generated an insulin secretion profile more like β-cells, in response to glucose. The PI3K/Akt pathway seems to play a negative role in IPC differentiation; however, the differentiation of ADSCs with exendin-4/activin A positively modulated the p38/MAPK pathway. Resveratrol medium activated the Jak/STAT3 pathway and generated IPCs apparently less sensitive to insulin and insulin-like receptors. Finally, the implant of IPCs with the best secretory behavior caused a decrease in hyperglycemia after one-week implantation in diabetic rats. Our data provide further information regarding the generation of IPCs from ADSCs and strengthen evidence to support the use of MSCs in regenerative medicine, specially the use of exendin-4/activin A to produce rapid and effectively IPCs with significant in vivo effects.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/20/10/2458Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/15775814ed504a4b912311355606b746Test

المؤلفون: Cynthia Roberts, Ruizhuo Ning, Poornima Venkat, Alex Zacharek, Michael Chopp, Tao Yan, Xinchun Ye, Jieli Chen

المصدر: International Journal of Molecular Sciences, Vol 14, Iss 11, Pp 22221-22232 (2013)

مصطلحات موضوعية: type-one diabetic rats, stroke, bone marrow stromal cells, Niaspan, white matter remodeling, synaptic plasticity, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Objective: White matter remodeling plays an important role in neurological recovery after stroke. Bone marrow stromal cells (BMSCs) and Niaspan, an agent which increases high density lipoprotein (HDL), each induces neurorestorative effects and promotes white matter remodeling after stroke in non-diabetic rats. In this study, we test whether combination of BMSCs with Niaspan induces an enhanced white matter remodeling in the ischemic brain of diabetic rats. Research design and methods: Type-1 diabetes (T1DM) rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated with or without BMSCs; Niaspan; and the combination of BMSCs + Niaspan daily for 14 days after MCAo. Immunostaining for white matter remodeling and synaptic protein expression including NG2; CNPase; BS (Bielschowsky silver); LFB (luxol fast blue); Synaptophysin and SMI-31 immunostaining were performed. Results: BMSC monotherapy did not regulate NG2 and CNPase expression compared to T1DM control rats. Both, combination of BMSCs + Niaspan treatment, and Niaspan monotherapy significantly increase NG2 and CNPase expression compared to T1DM control. While combination BMSC+Niaspan, BMSC monotherapy and Niaspan monotherapy groups all increase BS, LFB, synaptophysin, and SMI-31 expression in the ischemic brain compared to T1DM-MCAo control. In addition, the combination treatment significantly enhances LFB, SMI-31, and Synaptophysin expression compared to BMSC monotherapy. Conclusions: Combination treatment of stroke with BMSCs and Niaspan in T1DM rats increases white matter remodeling and additively increases BMSC monotherapy induced myelination and synaptic plasticity after stroke in T1DM rats.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/14/11/22221Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/5fd6105acd3441c6938c4b221302d35cTest

المؤلفون: Seung Hwan Jeon, Guan Qun Zhu, Woong Jin Bae, Sae Woong Choi, Hyun Cheol Jeong, Hyuk Jin Cho, U-Syn Ha, Sung-Hoo Hong, Ji Youl Lee, Eun Bi Kwon, Hyo-Jin Kim, Soon Min Lee, Hey-Yon Kim, Sae Woong Kim

المصدر: International Journal of Molecular Sciences, Vol 19, Iss 12, p 3730 (2018)

مصطلحات موضوعية: stromal cell-derived factor-1 expressing engineered mesenchymal stem cells, erectile dysfunction, intracavernosal injection, streptozotocin-induced diabetic rats, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague⁻Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/19/12/3730Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/2bb3849730a94da8a2250bc902ba2ad3Test

المؤلفون: Junjun Wang, Ting Zhai, Yong Chen

المصدر: International Journal of Molecular Sciences, Vol 19, Iss 3, p 815 (2018)

مصطلحات موضوعية: honokiol, type 2 diabetic rats, CYP450, transporter, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: This study was aimed to clarify the effect of honokiol (Hon) on the activity of Cytochrome P450 (CYP450) enzymes, and the level of mRNA expression of liver and kidney transporters in type 2 diabetic rats induced by high-fat diet and strepotozotocin. Rats were randomly divided into normal control (NC) group, diabetic control (DC) group and Hon groups (n = 6). The activities of hepatic CYP1A2, CYP2E1, CYP2C, CYP2B, CYP3A and CYP4A, and the mRNA expression levels of hepatic and renal transporters, were determined. Compared to the NC group, the activities of CYP1A2, CYP2E1, CYP4A and CYP2C in DC group were increased by 2.36-, 2.10-, 2.55- and 1.86-fold, respectively. The mRNA expression levels of hepatic Oat2, Oatp2b1 and Oatp1a5, and renal Oct1, Octn2, Oatp2b1 and Oatp1a5, were significantly down-regulated, while the mRNA expression levels of hepatic Octn2, Oatp3a1, Oatp1a1 and Mdr2, and renal Oat2, Mrp4 and Bcrp, were significantly upregulated. Compared to the DC group, Hon treatment significantly inhibited the activity of hepatic CYP2E1, CYP4A, 3A and CYP1A2 by 45.6%, 29.2%, 22.7% and 20.7% in Hon high dose group, respectively. Moreover, Hon treatment significantly inhibited the mRNA expression levels of renal Bcrp and Mrp4 by 2.63-fold and 1.54-fold, while significantly upregulated the mRNA expression levels of hepatic Oat2 and Oatp2b1 by 1.52-fold and 1.54-fold in Hon high dose group, respectively. The results suggested that under the diabetes condition, the changes of CYP450 activity and transporter expression inevitably interfere the normal transport, metabolism and efficacy of drugs. The present work firstly reported that Hon treatment ameliorated the abnormal change of hepatic CYP activity (including CYP2E1, CYP4A and CYP1A2) and the transporter mRNA expression (including hepatic Oat2 and Oatp2b1, renal Bcrp and Mrp4) in type 2 diabetic rats induced by high-fat diet and strepotozotocin, which are associated with the occurrence and development of diabetes.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/19/3/815Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/73e5ed184f8d491aa174696152a303ebTest

المؤلفون: Ângelo C. Salvador, Ewelina Król, Virgínia C. Lemos, Sónia A. O. Santos, Fernanda P. M. S. Bento, Carina P. Costa, Adelaide Almeida, Dawid Szczepankiewicz, Bartosz Kulczyński, Zbigniew Krejpcio, Armando J. D. Silvestre, Sílvia M. Rocha

المصدر: International Journal of Molecular Sciences, Vol 18, Iss 1, p 13 (2016)

مصطلحات موضوعية: diabetic rats, elderberry extracts supplementation, high-fat diet, lipophilic extract, polar extract, Sambucus nigra L., Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Elderberry (Sambucus nigra L.) lipophilic and polar extract dietary supplementation effects were evaluated according to diabetes management indices, using an in vivo model. A research pipeline was constructed, that ranged from extract preparation, partial chemical characterization and toxicity evaluation, to examining the elderberry extract dietary supplementation effects on biofluid and tissues. Extracts toxicity was screened using an Aliivibrio fischeri bioluminescence model. A concentration of up to 60 mg/L was selected, and rat doses for oral supplementation were computed applying the interspecies correlation between A. fischeri and rats. Wistar type 2 diabetic rats, induced by streptozotocin (STZ), were fed a high-fat diet and supplemented for 4 weeks at doses of 190 and 350 mg/kg body weight/day of lipophilic and polar extract, respectively. As far as we know, lipophilic elderberry extract supplementation was assessed for the first time, while polar extract was administrated at higher doses and for a shorter period compared to previous studies, aiming to evaluate subacute supplementation effects. The polar extract modulated glucose metabolism by correcting hyperglycemia, while the lipophilic extract lowered insulin secretion. Both extracts lowered insulin resistance, without remarkable alterations to hematological indices, sera lipids and sera and tissular trace element homeostasis. In conclusion, elderberries are a potential source of bioactive compounds for formulations to be used as co-adjuvants in diabetes management.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/18/1/13Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/c05edb64cdd04de3852b9c141685466fTest

المؤلفون: Hyun Cheol Jeong, Sae Woong Choi, Woong Jin Bae, Hyuk Jin Cho, Hyo-Jin Kim, Soon Min Lee, H. S. Kim, U-Syn Ha, Guan Qun Zhu, Sae Woong Kim, Seung Hwan Jeon, Ji Youl Lee, Sung-Hoo Hong, Eunbi Kwon

المصدر: International Journal of Molecular Sciences, Vol 19, Iss 12, p 3730 (2018)
International Journal of Molecular Sciences
Volume 19
Issue 12

مصطلحات موضوعية: 0301 basic medicine, Blood Glucose, Male, endocrine system diseases, Basic fibroblast growth factor, Gene Expression, Nitric Oxide Synthase Type I, lcsh:Chemistry, chemistry.chemical_compound, Phosphatidylinositol 3-Kinases, Cell Movement, Medicine, Stromal cell-derived factor 1, stromal cell-derived factor-1 expressing engineered mesenchymal stem cells, lcsh:QH301-705.5, Spectroscopy, biology, General Medicine, Computer Science Applications, Vascular endothelial growth factor, Genetic Engineering, medicine.drug, Signal Transduction, medicine.medical_specialty, streptozotocin-induced diabetic rats, Stromal cell, intracavernosal injection, Nitric Oxide Synthase Type III, erectile dysfunction, Neovascularization, Physiologic, Endothelial NOS, Mesenchymal Stem Cell Transplantation, Catalysis, Article, Diabetes Mellitus, Experimental, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Animals, Physical and Theoretical Chemistry, Molecular Biology, Protein kinase B, business.industry, Organic Chemistry, Body Weight, nutritional and metabolic diseases, Mesenchymal Stem Cells, Streptozotocin, medicine.disease, Chemokine CXCL12, Rats, Disease Models, Animal, 030104 developmental biology, Endocrinology, chemistry, lcsh:Biology (General), lcsh:QD1-999, biology.protein, business, Proto-Oncogene Proteins c-akt

الوصف: Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague&ndash
Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ±
0.07 in the normal group, 0.27 ±
0.08 in the DM ED group, 0.42 ±
0.11 in the DM ED + BM-MSC group, and 0.58 ±
0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p <
0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p <
0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p <
0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p <
0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p <
0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p <
0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e9b24305fc9392212ec07d6ebceb5a2Test
https://www.mdpi.com/1422-0067/19/12/3730Test

المؤلفون: Ewelina Król, Virgínia C Lemos, Bartosz Kulczyński, Zbigniew Krejpcio, Sónia A.O. Santos, Adelaide Almeida, Ângelo C. Salvador, Carina Pedrosa Costa, Sílvia M. Rocha, Dawid Szczepankiewicz, Fernanda P M S Bento, Armando J. D. Silvestre

المصدر: International Journal of Molecular Sciences, Vol 18, Iss 1, p 13 (2016)
International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 18; Issue 1; Pages: 13

مصطلحات موضوعية: Blood Glucose, Male, 0301 basic medicine, Pharmacology, Sambucus nigra, polar extract, lcsh:Chemistry, elderberry extracts supplementation, Aliivibrio fischeri, lcsh:QH301-705.5, Spectroscopy, biology, Chemistry, Sambucus nigra L, 04 agricultural and veterinary sciences, General Medicine, lipophilic extract, 040401 food science, Computer Science Applications, high-fat diet, Biochemistry, Toxicity, diabetic rats, medicine.drug, Carbohydrate metabolism, Diet, High-Fat, Streptozocin, Article, Catalysis, Diabetes Mellitus, Experimental, Inorganic Chemistry, 03 medical and health sciences, 0404 agricultural biotechnology, Insulin resistance, In vivo, medicine, Animals, Hypoglycemic Agents, Rats, Wistar, Physical and Theoretical Chemistry, Molecular Biology, Plant Extracts, Organic Chemistry, Streptozotocin, biology.organism_classification, medicine.disease, Rats, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Dietary Supplements, Insulin Resistance, Homeostasis

الوصف: Elderberry (Sambucus nigra L.) lipophilic and polar extract dietary supplementation effects were evaluated according to diabetes management indices, using an in vivo model. A research pipeline was constructed, that ranged from extract preparation, partial chemical characterization and toxicity evaluation, to examining the elderberry extract dietary supplementation effects on biofluid and tissues. Extracts toxicity was screened using an Aliivibrio fischeri bioluminescence model. A concentration of up to 60 mg/L was selected, and rat doses for oral supplementation were computed applying the interspecies correlation between A. fischeri and rats. Wistar type 2 diabetic rats, induced by streptozotocin (STZ), were fed a high-fat diet and supplemented for 4 weeks at doses of 190 and 350 mg/kg body weight/day of lipophilic and polar extract, respectively. As far as we know, lipophilic elderberry extract supplementation was assessed for the first time, while polar extract was administrated at higher doses and for a shorter period compared to previous studies, aiming to evaluate subacute supplementation effects. The polar extract modulated glucose metabolism by correcting hyperglycemia, while the lipophilic extract lowered insulin secretion. Both extracts lowered insulin resistance, without remarkable alterations to hematological indices, sera lipids and sera and tissular trace element homeostasis. In conclusion, elderberries are a potential source of bioactive compounds for formulations to be used as co-adjuvants in diabetes management.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::42076b28f6bfb083942e85b16ab0942fTest
https://doi.org/10.3390/ijms18010013Test