Dysfunctional HDL in HIV-Infected Adults With Suppressed Viremia on Antiretroviral Therapy May Directly Increase mRNA Expression Of CXCL16 and Sialoadhesin in Monocytes

Abstract The ubiquitin-proteasome system modifies different cellular and protein functions. Its dysregulation may lead to disrupted proteostasis associated with multiple pathologies and aging. Pharmacological regulation of proteasome functions is already an important part of the treatment of several diseases. 1,4-dihydropyridine (1,4-DHP) derivatives possess different pharmacological activities, including antiaging and neuroprotective. The aim of this study was to investigate the effects of several 1,4-DHP derivatives on mRNA expression levels of proteasomal genes Psma3, Psmb5, and Psmc6 in several organs of rats. Rats were treated with metcarbatone, etcarbatone, glutapyrone, styrylcarbatone, AV-153-Na, or AV-153-Ca per os for three days. mRNA expression levels were determined with real-time polymerase chain reaction (PCR). For AV-153-Na and AV-153-Ca, we also determined the expression of the Psma6 gene. In the kidney, metcarbatone, etcarbatone, styrylcarbatone, and AV-153-Na increased the expression of all analysed genes. Glutapyrone increased the expression of Psmb5 and Psmc6 but did not affect the expression of Psma3. In the blood, glutapyrone increased Psmb5 expression. In the liver, AV-153-Na increased the expression of Psma6 and Psmc6 but lowered the expression of Psmb5, while AV-153-Ca only increased Psma6 expression. The ability of 1,4-DHP derivatives to increase the expression of proteasome subunit genes might hold a therapeutic potential in conditions associated with impaired proteasomal functions, but further research is needed.

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(−)-Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

Molecules ◽

10.3390/molecules23123221 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3221 ◽

Cited By ~ 18

Author(s):

Sung-Yen Lin ◽

Lin Kang ◽

Chau-Zen Wang ◽

Han Huang ◽

Tsung-Lin Cheng ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Alkaline Phosphatase ◽

Mesenchymal Stem Cells ◽

Bone Loss ◽

Osteogenic Differentiation ◽

Mrna Expression ◽

Human Bmscs ◽

Marrow Mesenchymal Stem Cells ◽

Increase Mrna Expression

Osteoporosis is the second most-prevalent epidemiologic disease in the aging population worldwide. Cross-sectional and retrospective evidence indicates that tea consumption can mitigate bone loss and reduce risk of osteoporotic fractures. Tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis in vitro. Previously, we showed that (−)-epigallocatechin-3-gallate (EGCG), one of the green tea polyphenols, increased osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) by increasing the mRNA expression of osteogenesis-related genes, alkaline phosphatase activity and, eventually, mineralization. We also found that EGCG could mitigate bone loss and improve bone microarchitecture in ovariectomy-induced osteopenic rats, as well as enhancing bone defect healing partially via bone morphogenetic protein 2 (BMP2). The present study investigated the effects of EGCG in human BMSCs. We found that EGCG, at concentrations of both 1 and 10 µmol/L, can increase mRNA expression of BMP2, Runx2, alkaline phosphatase (ALP), osteonectin and osteocalcin 48 h after treatment. EGCG increased ALP activity both 7 and 14 days after treatment. Furthermore, EGCG can also enhance mineralization two weeks after treatment. EGCG without antioxidants also can enhance mineralization. In conclusion, EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes including Runx2, ALP, osteonectin and osteocalcin. EGCG further increased ALP activity and mineralization. Loss of antioxidant activity can still enhance mineralization of human BMSCs (hBMSCs).

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Cytokine Expression in the Colonic Mucosa of Human Immunodeficiency Virus-Infected Individuals before and during 9 Months of Antiretroviral Therapy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00250-08 ◽

2008 ◽

Vol 52 (9) ◽

pp. 3377-3384 ◽

Cited By ~ 23

Author(s):

Hubert Schulbin ◽

Hagen Bode ◽

Hartmut Stocker ◽

Wolfgang Schmidt ◽

Thomas Zippel ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

T Lymphocytes ◽

Mrna Expression ◽

Colonic Mucosa ◽

Mrna Levels ◽

Ifn Gamma ◽

Hiv Rna ◽

Tnf Α ◽

Immunodeficiency Virus

ABSTRACT High-level human immunodeficiency virus (HIV) replication and the rapid breakdown of the mucosal immune system are the hallmarks of HIV infection in the gut. Cytokine dysregulation may be related to both phenomena. Using real-time PCR we quantified the colonic mucosal mRNA expression of selected proinflammatory and regulatory (gamma interferon [IFN-gamma], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2], IL-4, IL-6, and IL-10) and HIV-inhibitory (IL-16, CCL3, and CCL5) cytokines for 10 HIV-infected patients before and during 9 months of highly active antiretroviral therapy (HAART). HIV RNA and T-cell dynamics were measured in the colonic mucosa and the blood. Seven HIV-negative individuals served as controls. The mucosal mRNA expression of TNF-α, IFN-gamma, IL-4, IL-6, and IL-10 was significantly higher in HIV-infected patients than in control patients and remained elevated during 9 months of HAART despite the decline in blood and mucosal HIV RNA levels and an increase in the level of CD4+ T lymphocytes. The mRNA levels of CCL3 and CCL5, both of which were elevated before treatment, returned to nearly normal during therapy. Despite reductions in levels of mucosal HIV RNA and the restoration of mucosal CD4+ T lymphocytes, antiretroviral therapy failed to restore the normal colonic immunologic environment.

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