Background There is a paucity of information available for clinical decision making applying to the elderly patient population. Therefore, data of percutaneous coronary interventions (PCI) including demographic inform...Background There is a paucity of information available for clinical decision making applying to the elderly patient population. Therefore, data of percutaneous coronary interventions (PCI) including demographic information on the elderly patients, procedural practices, and outcomes are needed. Objectives and Methods From consecutive PCIs of participating institutions, demographics data, clinical, angiographic success and adverse clinical outcomes were collected. Standard statistical methods were used to compare crude differences in patient and procedural characteristics across age groups. Results At baseline, the prevalence of comorbid conditions ( renal failure and heart failure) increased with age. Unstable angina or a non-ST elevation MI were the most common indications for PCI across all age groups. Fewer patients ≥ 80 years old were undergoing primary PCI and older patients were somewhat less likely to receive a Ⅱb/Ⅲa receptor blocker. Slightly more patients ≥ 80 years old underwent a 2-vessel PCI ( consistent with them having more multivessel disease) and these patients were more likely to have an intervention on a Type C lesion. Compared to patients < 50 years old, those aged ≥ 70 years old had a significantly increased risk of death, MI, stroke, or vascular complications at the access site. Conclusions This study suggests increasing age is associated with increasing risk for an adverse outcome following PCI. This is in part attributable to case-mix but likely, also related to the changing physiology of aging. Despite the increased risk of the procedure, the clinical success rate for PCI is quite high and makes it a reasonable alternative for the treatment of CAD in the elderly.展开更多
Dietary phenolic compounds (PCs) have been receiving intercst lor their presumcd roles ill disease prevention. However, there is a lack of studies on the underlying molecular mechanisnls. In this regard, in vitro me...Dietary phenolic compounds (PCs) have been receiving intercst lor their presumcd roles ill disease prevention. However, there is a lack of studies on the underlying molecular mechanisnls. In this regard, in vitro metabolomic approaches are suitable for the investigation o1 the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been cxalnined for PCs from rosemary (Rosmarinus officinalis), olive oil, and reSVCl-atrol using cell-based mctabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vi[ro cell experiment in some cases. Our integral analysis of the reviewed studies suggest that PCs may be involved not only in basic cellular processes or macro-and micro-nutrient meta- bolism, but also in specific metabolic pathways that have been thoroughly investigated. These modulated pathways could have a clinical impact on neurodegenerativc diseases, type 2 diabetes, cancer, and cardiovascular diseases. In conclusion, the in vitro metabolomic approaches provide additional information of the molecular mechanisms involved in disease risk reduction of dietary PCs. In order to elucidate the mechanisms of action of PCs, more metabolomic cell-based studies are nccdcd and testing the physiological conjugated forms of PCs in these cell systems could be of special interest.展开更多
Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial–mesenchymal transition(pEMT),proliferation,and further redifferentiation into specialized tubule epithelial...Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial–mesenchymal transition(pEMT),proliferation,and further redifferentiation into specialized tubule epithelial cells(TECs).Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase(PPIase)activity of cyclophilin(Cyp)proteins,we hypothesized that cyclophilins could regulate TEC phenotype.Here we demonstrate that in cultured TECs,CypA silencing triggers loss of epithelial features and enhances transforming growth factorβ(TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail.This pro-epithelial action of CypA relies on its PPIase activity.By contrast,CypB emerges as an epithelial repressor,because CypB silencing promotes epithelial differentiation,prevents TGFβ-induced EMT,and induces tubular structures in 3D cultures.In addition,in the kidneys of CypB knockout mice subjected to unilateral ureteral obstruction,inflammatory and pro-fibrotic events were attenuated.CypB silencing/knockout leads to Slug,but not Snail,downregulation.CypB support of Slug expression depends on its endoplasmic reticulum location,where it interacts with calreticulin,a calcium-buffering chaperone related to Slug expression.As CypB silencing reduces ionomycin-induced calcium release and Slug upregulation,we suggest that Slug expression may rely on CypB modulation of calreticulin-dependent calcium signaling.In conclusion,this work uncovers new roles for CypA and CypB in modulating TEC plasticity and identifies CypB as a druggable target potentially relevant in promoting kidney repair.展开更多
文摘Background There is a paucity of information available for clinical decision making applying to the elderly patient population. Therefore, data of percutaneous coronary interventions (PCI) including demographic information on the elderly patients, procedural practices, and outcomes are needed. Objectives and Methods From consecutive PCIs of participating institutions, demographics data, clinical, angiographic success and adverse clinical outcomes were collected. Standard statistical methods were used to compare crude differences in patient and procedural characteristics across age groups. Results At baseline, the prevalence of comorbid conditions ( renal failure and heart failure) increased with age. Unstable angina or a non-ST elevation MI were the most common indications for PCI across all age groups. Fewer patients ≥ 80 years old were undergoing primary PCI and older patients were somewhat less likely to receive a Ⅱb/Ⅲa receptor blocker. Slightly more patients ≥ 80 years old underwent a 2-vessel PCI ( consistent with them having more multivessel disease) and these patients were more likely to have an intervention on a Type C lesion. Compared to patients < 50 years old, those aged ≥ 70 years old had a significantly increased risk of death, MI, stroke, or vascular complications at the access site. Conclusions This study suggests increasing age is associated with increasing risk for an adverse outcome following PCI. This is in part attributable to case-mix but likely, also related to the changing physiology of aging. Despite the increased risk of the procedure, the clinical success rate for PCI is quite high and makes it a reasonable alternative for the treatment of CAD in the elderly.
基金supported by grants(Grant Nos.AGL2009-13517-C03-03 and AGL2012-40144-C03-02)from the Spanish Ministry of EducationScience(Ministerio de Educacion y Ciencia,Spain),a Sara Borrell post-doctoral grant(CD14/00275+3 种基金Spain)a Pla estrategic de recerca i innovacio en salut(PERIS)post-doctoral grant(SLT002/16/00239Catalunya,Spain)support of Institut d’InvestigacioSanitaria Pere Virgili(IISPV)and Centre Tecnologic de Nutricio i Salut(CTNS),Reus,Spain
文摘Dietary phenolic compounds (PCs) have been receiving intercst lor their presumcd roles ill disease prevention. However, there is a lack of studies on the underlying molecular mechanisnls. In this regard, in vitro metabolomic approaches are suitable for the investigation o1 the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been cxalnined for PCs from rosemary (Rosmarinus officinalis), olive oil, and reSVCl-atrol using cell-based mctabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vi[ro cell experiment in some cases. Our integral analysis of the reviewed studies suggest that PCs may be involved not only in basic cellular processes or macro-and micro-nutrient meta- bolism, but also in specific metabolic pathways that have been thoroughly investigated. These modulated pathways could have a clinical impact on neurodegenerativc diseases, type 2 diabetes, cancer, and cardiovascular diseases. In conclusion, the in vitro metabolomic approaches provide additional information of the molecular mechanisms involved in disease risk reduction of dietary PCs. In order to elucidate the mechanisms of action of PCs, more metabolomic cell-based studies are nccdcd and testing the physiological conjugated forms of PCs in these cell systems could be of special interest.
基金supported in part by grants from Ministerio de Cienciae Innovacion(SAF 201459945-Rand SAF 201789989-R to A.M.)the Fundacion Senefro(SEN 2019 to A.M.),Instituto de Salud Carloslll(PIE13/00027)Red de Investigacion Renal REDinREN(12/0021/0013).KAN.is supported by Nationa Mnstitutes of Health(NIH)DK 47060.A.M.group holds the Quality Mention from the Generalitat de Catalunya(2017 SGR).
文摘Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial–mesenchymal transition(pEMT),proliferation,and further redifferentiation into specialized tubule epithelial cells(TECs).Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase(PPIase)activity of cyclophilin(Cyp)proteins,we hypothesized that cyclophilins could regulate TEC phenotype.Here we demonstrate that in cultured TECs,CypA silencing triggers loss of epithelial features and enhances transforming growth factorβ(TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail.This pro-epithelial action of CypA relies on its PPIase activity.By contrast,CypB emerges as an epithelial repressor,because CypB silencing promotes epithelial differentiation,prevents TGFβ-induced EMT,and induces tubular structures in 3D cultures.In addition,in the kidneys of CypB knockout mice subjected to unilateral ureteral obstruction,inflammatory and pro-fibrotic events were attenuated.CypB silencing/knockout leads to Slug,but not Snail,downregulation.CypB support of Slug expression depends on its endoplasmic reticulum location,where it interacts with calreticulin,a calcium-buffering chaperone related to Slug expression.As CypB silencing reduces ionomycin-induced calcium release and Slug upregulation,we suggest that Slug expression may rely on CypB modulation of calreticulin-dependent calcium signaling.In conclusion,this work uncovers new roles for CypA and CypB in modulating TEC plasticity and identifies CypB as a druggable target potentially relevant in promoting kidney repair.