名医介绍

张菁

博士、主任药师、教授、博士研究生导师

专长临床药理学研究、定量药理学研究

复旦大学附属华山医院抗生素研究所副所长

卫健委抗生素临床药理重点实验室主任

华山医院药物临床试验机构常务副主任

期临床研究室主任上海市领军人才

上海市首届“医树奖”获得者

中国药理学会化疗药理专委会副主委

上海医学会感染与化疗分会主委

上海药学会药物临床研究专委会主委

上海药学会抗生素专委会副主委

吕晓菊

博士、主任医师、教授、博士研究生导师

四川大学华西医院感染病中心副主任

长期从事感染性疾病医教研及医疗管理工作

卫健委合理用药专委会抗菌药物学组委员

卫健委全国细菌耐药监测网专委会委员

中国药学会抗生素专业委员会副主任委员

中华医学会细菌感染与耐药防治专委会常委

中国医药教育协会真菌感染专委会常委

中华医学会感染病学专业委员会委员

负责或主研国家纵横向课题40余项

多个国内外杂志编委或编审专家

发表论文160余篇，著书20余部，培养硕士、博士研究生30余名

王贵强

教授，主任医师，博士研究生导师

中央保健会诊专家

北京大学第一医院感染疾病科主任，兼任肝病中心主任

中华医学会感染病学分会前任主任委员

中国医院协会抗菌药物合理应用工作委员会主任委员

中国医师协会感染病医师分会副会长

中华医学会全科医师教育学院副院长

国家免疫规划专家咨询委员会委员

国家卫健委传染病标准委员会委员

国务院应对新冠肺炎联防联控机制医疗救治专家组成员

国家卫健委新冠病毒肺炎恢复期血浆治疗专家组成员

国家卫健委境外抗疫医疗专家组国家顾问团成员

国务院应对新冠肺炎联防联控机制科研攻关专家组成员

科技部新冠肺炎国际合作专家组成员

美国《临床感染病》杂志编委，《中华传染病杂志》和《中华临床感染病杂志》副总编辑，《临床肝胆病学》共同主编等。

冉兴无

主任医师，教授，博士研究生导师

四川大学华西医院内分泌代谢科副主任

四川大学华西医院糖尿病足诊治中心主任

四川大学华西医院血管中心糖尿病周围血管病变分中心主任

四川省卫生厅学术技术带头人

四川省学术技术带头人

四川省卫生计生委领军人才

中华医学会糖尿病分会常务委员

中华预防医学会组织感染与损伤预防与控制专业委员会副主任委员

中国医师协会内科培训专业指导委员会副主任委员

中华医学会糖尿病分会糖尿病足病工作组组长

西部精神医学协会内分泌暨糖尿病专业委员会主任委员

四川省医学会内分泌暨糖尿病专业委员会主任委员

四川省医学会糖尿病周围血管病变暨足病学组组长

四川省医学会内科专业委员会常务委员兼代谢病学组组长

四川省医师协会内分泌代谢专科医师专业委员会副主任委员。

第2页共27页

K2 Content

GLP1R Gene Expression and Kidney Disease Progression 2024-11-04 00:00

Jefferson L. Triozzi, MD, MSCI; Zhihong Yu, MS, PhD; Ayush Giri, MS, PhD; Hua-Chang Chen, PhD; Otis D. Wilson, BBA; Brian Ferolito, MS; T. Alp Ikizler, MD; Elvis A. Akwo, MD, MS; Cassianne Robinson-Cohen, PhD; John Michael Gaziano, MD, MPH; Kelly Cho, PhD, MPH; Lawrence S. Phillips, MD; Ran Tao, PhD; Alexandre C. Pereira, MD, PhD; Adriana M. Hung, MD, MPH; for the VA Million Veteran Program

Key Points

Question Are glucagon-like peptide 1 receptor agonists (GLP-1RAs) associated with kidney disease progression?

Findings In this genetic association study of 353 153 adults, higher genetic GLP1R gene expression as a proxy for GLP-1RAs was associated with a small reduction in the risk of kidney disease progression, even after adjusting for obesity and diabetes.

Meaning These findings support a nephroprotective role of GLP-1RAs.

Abstract

IMPORTANCE Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control.

OBJECTIVE To investigate the association of genetically proxied GLP-1RAs with kidney disease

DESIGN, SETTING, AND PARTICIPANTS This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024.

EXPOSURES Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project.

MAIN OUTCOMES AND MEASURES The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression.

RESULTS Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status.

CONCLUSIONS AND RELEVANCE In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.
Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations 2024-10-31 00:00

Daniela Milosheska . Robert Roskar

Received: August 17, 2022 / Accepted: September 6, 2022 / Published online: October 11, 2022

©The Author(s) 2022

ABSTRACT

Nowadays, numerous skincare routines are used to rejuvenate aging skin. Retinoids are one of the most popular ingredients used in antiaging treatments. Among the representatives of retinoids, tretinoin is considered the most effective agent with proven antiaging effects on the skin and can be found in formulations approved as medicines for topical treatment of acne, facial wrinkles, and hyperpigmentation. Other retinoids present in topical medicines are used for various indications, but only tazarotene is also approved as adjunctive agent for treatment of facial fine wrinkling and pigmentation. The most commonly used retinoids such as retinol, retinaldehyde, and retinyl palmitate are contained in cosmeceuticals regulated as cosmetics. Since clinical efficacy studies are not required for marketing cosmetic formulations, there are concerns about the efficacy of these retinoids.

From a formulation perspective, retinoids pose a challenge to researchers as a result of their proven instability, low penetration, and potential for skin irritation. Therefore, novel delivery systems based on nanotechnology are being developed to overcome the limitations of conventional formulations and improve user compliance. In this review, the clinical evidence for retinoids in conventional and nanoformulations for topical antiaging treatments was evaluated. In addition, an overview of the comparison clinical trials between tretinoin and other retinoids is presented. In general, there is a lack of evidence from properly designed clinical trials to support the claimed efficacy of the most commonly used retinoids as antiaging agents in cosmeceuticals. Of the other retinoids contained in medicines, tazarotene and adapalene have clinically evaluated antiaging effects compared to tretinoin and may be considered as potential alternatives for antiaging treatments. The promising potential of retinoid nanoformulations requires a more comprehensive evaluation with additional studies to support the preliminary findings.

Keywords: Antiaging; Clinical evidence; Cosmeceuticals; Nanoformulations; Retinoids; Retinol; Tretinoin

Key Summary Points

Tretinoin is the retinoid present in medicines for topical application with the strongest clinical evidence of antiaging Tazarotene and adapalene may be considered as tretinoin alternatives for antiaging treatments.

Clinical evidence is lacking for retinoids contained in cosmeceuticals for topical antiaging treatments.

Novel formulations based on nanotechnology are being developed to overcome the major drawbacks of retinoid Further evaluation with in vivo testing and clinical trials are needed to support the preclinical results for the developed nanoformulations containing retinoids.

D. Milosheska INSLAB, Maribor, Slovenia

R. Roskar (&)

University of Ljubljana, Faculty of Pharmacy, Askerceva cesta 7, 1000 Ljubljana, Slovenia

e-mail: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。
Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations 2024-10-30 00:00

Gérald J. Prud’homme1,2 *, Mervé Kurt 2 and Qinghua Wang3,4

1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada,

2 Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON, Canada,

3 Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China,

4 Shanghai Yinuo Pharmaceutical Co., Ltd., Shanghai, China

Edited by:

Cátia F. Lourenço, University of Coimbra, Portugal

Reviewed by:

Mujib Ullah, Stanford University, United States Taylor Landry, East Carolina University, United States

*Correspondence:

Gérald J. Prud’homme 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Specialty section:

This article was submitted to Molecular Mechanisms of Aging, a section of the journal Frontiers in Aging

Received: 28 April 2022

Accepted: 06 June 2022

Published: 12 July 2022

Citation:

Prud’homme GJ, Kurt M and Wang Q (2022) Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations. Front. Aging 3:931331.

doi: 10.3389/fragi.2022.931331

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan. In humans, Klotho levels decline with age, chronic kidney disease, diabetes, Alzheimer’s disease and other conditions. Low Klotho levels correlate with an increase in the death rate from all causes. Klotho acts either as an obligate coreceptor for fibroblast growth factor 23 (FGF23), or as a soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced in the kidneys, but also in the brain, pancreas and other tissues. On renal tubular-cell membranes, it associates with FGF receptors to bind FGF23. Produced in bones, FGF23 regulates renal excretion of phosphate (phosphaturic effect) and vitamin D metabolism. Lack of Klotho or FGF23 results in hyperphosphatemia and hypervitaminosis D. With age, human renal function often deteriorates, lowering Klotho levels. This appears to promote age-related pathology. Remarkably, Klotho inhibits four pathways that have been linked to aging in various ways: Transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), Wnt and NF-κB. These can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis and neoplasia. Furthermore, Klotho increases cell-protective antioxidant enzymes through Nrf2 and FoxO. In accord, preclinical Klotho therapy ameliorated renal, cardiovascular, diabetes-related and neurodegenerative diseases, as well as cancer. s-Klotho protein injection was effective, but requires further investigation. Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In clinical trials, increased Klotho was noted with renin-angiotensin system inhibitors (losartan, valsartan), a statin (fluvastatin), mTOR inhibitors (rapamycin, everolimus), vitamin D and pentoxifylline. In preclinical work, antidiabetic drugs (metformin, GLP-1-based, GABA, PPAR-γ agonists) also enhanced Klotho. Several traditional medicines and/or nutraceuticals increased Klotho in rodents, including astaxanthin, curcumin, ginseng, ligustilide and resveratrol. Notably, exercise and sport activity increased Klotho. This review addresses molecular, physiological and therapeutic aspects of Klotho.

Keywords: aging, FGF23, hyperphosphatemia, klotho, IGF-1, NF-KappaB, TGF-beta, Wnt

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主任医师、教授、博导，南方医科大学第三附属医院（广东省骨科医院）院长

张菁

吕晓菊

王贵强

冉兴无

学术会议

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主任医师、教授、博导，南方医科大学第三附属医院（广东省骨科医院）院长

张菁

吕晓菊

王贵强

冉兴无

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学术会议

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