The UBR5 protein facilitates mesangial cell hypertrophy and glycolysis induced by high glucose by increasing the phosphorylation levels of AKT

Lin Liao1  · Qiming Xu2  · Jie Xu3  · Jie Chen1  · Wenrui Liu1  · Wenhao Chen1  · Yunqing Tang1  · Lianxiang Duan1  · Yue Guo1  · Ziyang Liu1  · Pengyu Tao2  · Yu Cao2  · Jianrao Lu1  · Jing Hu1,4

Received: 14 June 2024 / Accepted: 31 January 2025 / Published online: 13 February 2025 © The Author(s) 2025

Abstract

Aims One of the primary pathological features in the early stages of diabetic nephropathy is mesangial cell (MC) hypertro-phy in the glomerulus. Considering the role of E3 ubiquitin ligases in regulating MC hypertrophy, the aim of this study was to identify the functional ubiquitin protein ligase E3 component N-recognin 5 (UBR5) during MC hypertrophy under high glucose conditions.

Methods Human MCs (HMCs) transduced with UBR5 silencing or overexpression vector were treated with high glucose, AKT inhibitor, or glycolysis inhibitor. Cell proliferation, cell cycle, hypertrophy and glycolysis were evaluated in the HMCs after indicated treatment. m6A methylated RNA immunoprecipitation, luciferase reporter assay, and RNA immunoprecipi-tation were performed to determine the regulation of UBR5 by Wilms tumor 1-associating protein (WTAP)/insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) induced m6A modification. Western blot was performed to determine the protein expression levels.

Results UBR5 expression was upregulated in db/db mice and in high glucose-induced HMCs. UBR5 silencing inhibited high glucose-induced HMC cell cycle arrest, cell hypertrophy, and glycolysis. UBR5 facilitated HMC hypertrophy and gly colysis by promoting the phosphorylation levels of AKT. Additionally, the promoting effect of glycolysis on cell hypertrophy were also elucidated. Further investigation into upstream regulators revealed that WTAP promoted m6A modification of UBR5 through the m6A reader IGF2BP1.

Conclusions Our study unveils a novel mechanism involved in high glucose-induced cell hypertrophy, offering new insights into the understanding and treatment of early pathological mechanisms in diabetic nephropathy.

Keywords High glucose · Hypertrophy · Glycolysis · UBR5, AKT phosphorylation

HbA1c variability as an independent risk factor for diabetic retinopathy: results from a screening program

Maria Ida Maiorino1,2  · Carlo Gesualdo3,4  · Silvia Angelino5  · Settimio Rossi3  · Nicole Di Martino2  · Clemente Iodice3,5  · Miriam Longo1,4  · Lorenzo Scappaticcio1,2  · Giuseppe Bellastella1,2  · Francesca Simonelli3  · Katherine Esposito1,2,5

Received: 4 January 2026 / Accepted: 6 May 2026 © The Author(s) 2026

Abstract

Aims To investigate the independent association between long-term glycemic variability, measured as the coefficient of variation (CV) of HbA1c, and the presence of diabetic retinopathy (DR) in a cohort of adults with diabetes within a system-atic eye screening program.

Methods This study screened 379 adults with type 1 and type 2 diabetes. Long-term glycemic variability was calculated as the CV of serial HbA1c measurements. DR was assessed via dilated fundus photography. The association between HbA1c CV and DR was analyzed using multivariable logistic regression adjusting for confounders.

Results DR incidence of 12.4%, mostly mild non-proliferative. The median HbA1c CV was 7.0% (53 mmol/mol). In unad-justed bivariate analysis, the incidence of mild DR was higher in the low- glycemic variability group (CV<5%) compared to the high- glycemic variability group. However, the multivariable logistic regression analysis revealed that higher HbA1c CV was independently associated with the presence of DR (β=0.643, P=0.042), alongside diabetes duration (P<0.001) and age (P<0.001).

Conclusions In conclusion, in a cohort of individuals with both type 1 and type 2 diabetes and a low incidence of DR, long-term glycemic variability, estimated as HbA1c CV, was independently associated with an increased risk of this complication.

Keywords Diabetic retinopathy · Glucose variability · Type 1 diabetes · Type 2 diabetes · Retinopathy screening · HbA1c coefficient of variation

中国人群中面部年轻化治疗专家共识

中国整形美容协会面部年轻化分会 中国整形美容协会抗衰老分会

中国整形美容协会医美线技术分会

通信作者:李勤,Email: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。

【摘要】 随着年龄的增长,中面部深层脂肪逐渐萎缩,浅层脂肪逐渐移位,眶区、上颌骨逐渐老化,中面部是面部老化最早出现的部位之一,也是实现年轻化外观的重要部位。由中国整形美容协会面部年轻化分会、抗衰老分会、医美线技术分会组织部分专家对中国人群中面部年轻化治疗的诸多问题进行了研讨,并形成共识。主要内容包括,中国人群中面部定义、中面部老化特征及评估方法、常见治疗方式(微创注射技术、光电技术、美塑疗法、埋线技术、脂肪填充、手术治疗)等,并针对中面部不同老化特点采用的联合治疗方案进行了推荐。

【关键词】 中面部; 年轻化; 治疗; 专家共识; 中国 DOI:10.3760/cma.j.issn.1671-0290.2020.01.001

中面部是面部老化最早出现的部位之一,是实现年轻化外观的重要部位。近年来,随着大众审美需求的提高,中国美容就医者对中面部年轻化的诉求增多,亟须规范中面部年轻化治疗。为此,由中国整形美容协会面部年轻化分会、抗衰老分会、医美线技术分会组织部分专家,参考中面部年轻化文章,结合现状和专家的经验,制定针对中国人中面部年轻化治疗的专家共识。希望通过共识为优化中国人中面部年轻化治疗提供指导意见,以期推进中面部年轻化治疗的规范管理。

寻常痤疮临床严重度分级及疗效评价 中国专家共识（2025版）

中国医师协会皮肤科医师分会痤疮学组 中国研究型医院学会皮肤科学专业委员会 中国中西医结合学会皮肤性病专业委员会痤疮学组 通信作者：鞠强，Email：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。；顾恒，Email：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。；郑志忠， Email：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。

【摘要】 寻常痤疮（简称痤疮）是皮肤科常见的损容性皮肤病，临床表现多样。痤疮存在多种临 床严重度分级方法，但如何客观地评价疾病严重程度并用于指导痤疮治疗方案的选择，以及如何科 学评价各种治疗方式在痤疮治疗中的疗效目前仍缺乏统一标准，也是临床医生极为关注的问题。为此，中国医师协会皮肤科医师分会痤疮学组、中国研究型医院学会皮肤科学专业委员会、中国中西医结合学会皮肤性病专业委员会痤疮学组组织我国痤疮诊疗领域部分专家，在广泛讨论的基础上制订《寻常痤疮临床严重度分级及疗效评价中国专家共识》，供皮肤科医师临床应用参考。【关键词】 寻常痤疮；治疗；严重度分级；疗效评价；专家共识 DOI：10.35541/cjd.20250034

Chinese expert consensus on clinical severity grading and therapeutic evaluation of acne vulgaris （2025 edition）

Acne Study Group of China Dermatologist Association; Dermatology Professional Committee of Chinese Research Hospital Association; Acne Study Group of Dermatology and Venereology Professional Committee of Chinese Association of Integrative Medicine

Corresponding authors: Ju Qiang, Email: 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。; Gu Heng, Email: 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。; Zheng Zhizhong, Email: 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。

【Abstract】 Acne vulgaris （abbreviated as acne） is a common aesthetic ⁃ impairing dermatological disease that markedly affects appearance, and is characterized by diverse clinical manifestations. At present, there are various grading systems for acne severity, while there is still a lack of unified standards for objectively assessing disease severity to guide treatment selection and scientifically evaluating the efficacy of acne therapies, which are also highly concerned issues for clinicians. To address this, the Acne Study Group of China Dermatologist Association, the Dermatology Professional Committee of Chinese Research Hospital Association, and the Acne Study Group of Dermatology and Venereology Professional Committee of Chinese Association of Integrative Medicine organized a group of experts in the field of acne diagnosis and treatment in China to develop the "Chinese expert consensus on clinical severity grading and therapeutic evaluation of acne vulgaris" after extensive discussions, aiming to provide a reference for dermatologists in clinical practice.

【Key words】 Acne vulgaris; Treatment; Clinical severity grading; Therapeutic evaluation; Expert consensus DOI: 10.35541/cjd.20250034

Comprehensive Approaches to Diagnosis and Treatment of Sensitive Skin

Hye One Kim 1,* , Ji Young Um 1,* , Han Bi Kim 1 , So Yeon Lee 1 , Hyun Choi 2 , Jihye Kim 3 , Eunbi Ko 3 , Bo Young Chung 1 , Chun Wook Park 1

1 Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea

2 Make-up Lab, R&D Center, Kolmar Korea, Seoul, Korea

3 Clinical Research Lab, Amorepacific R&I Center, Yongin, Korea

ABSTRACT

Sensitive skin (SS) is increasingly recognized as a complex syndrome characterized by discom-fort and heightened sensitivity to otherwise harmless stimuli, such as environmental changes, physical contact, and cosmetic products. This condition poses challenges in both diagnosis and treatment due to its variable presentation and subjective nature. The pathophysiological features of SS include neurogenic inflammation and small fiber neuropathy, largely driven by the hyperactivation of sensory nerves. This hyperactivation is closely associated with transient receptor potential (TRP) channels, particularly TRPV1, which contribute to the exaggerated sensory responses seen in SS. Furthermore, psychological factors like stress and anxiety, along with environmental stressors such as pollution and ultraviolet exposure, play significant roles in exacerbating symptoms. The diverse and individualized responses to stimuli make it difficult to establish standardized diagnostic criteria for SS, necessitating a combination of subjective diagnostic tools (e.g., the Sensitive Scale-10) and objective assessments (e.g., transepidermal water loss and lactic acid sting test) to accurately identify and assess SS. This paper provides a comprehensive review of SS, covering its definition, prevalence, pathogenesis, diagnostic challenges, and management strategies, and highlights the importance of personalized care in effectively managing SS and improving patient quality of life.

Keywords: Skin diseases; Skin irritancy tests; Skin physiological phenomena; Pruritus; Pathophysiology; Sensitive Scale-10; Sensitive skin

Cai’s herbal tea enhances mitochondrial autophagy of type 1 diabetic mellitus β cells through the AMPK/mTOR pathway and alleviates inflammatory response

Hongchun Li¹ ·Yanfei Gao² · Mengdi Li¹ ·Yue Dong¹ · Jie Chen³ · Bingyue Zhang³ · Kaiqiang Li⁴ ·Yuqun Cai³

Received: 11 January 2024 / Accepted: 30 May 2024 / Published online: 2 July 2024©The Author(s) 2024

Abstract

Background This study investigates the therapeutic mechanisms of Cai’s Herbal Tea in Type 1 Diabetes Mellitus (T1DM) mice,focusing on its effects on mitochondrial change and autophagy via the AMP-activated protein kinase (AMPK)—mammalian target of rapamycin (mTOR) pathway.

Methods The composition of Cai’s Herbal Tea was analyzed by Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-Q/TOF-MS). C57BL/6 mice and Min6 pancreatic beta cells were divided into control, diabetic mellitus (DM)/high glucose (HG), and treatment groups (low, medium, and high doses of Cai’s Tea, and Metformin). Key physiological parameters, pancreatic islet health, Min6 cell morphology, viability, and insulin (INS) secretion were assessed. Small Interfering RNA-AMPK (si-AMPK) was utilized to confirm the pathway involvement. Results Cai’s Herbal Tea improved body weight, pancreatic islet pathological injury, and INS secretion whereas reduced total triglycerides, fasting blood sugar, and Interferon gamma (INF-γ) in T1DM mice,particularly at higher doses. In Min6 cells, Cai’s Tea mitigated HG-induced damage and proinflammatory response, enhancing cell viability and INS secretion. Notably, it reduced swelling and improved cristae structure in treated groups of mitochondria and promoted autophagy via the AMPK-mTOR pathway, evidenced by increased LC3II/LC3I and P-AMPK/AMPK ratios, and decreased P-mTOR/ mTOR and P62 expressions in pancreatic islet β-cells.Furthermore,these effects were converted by si-AMPK interference. Conclusion Cai’s Herbal Tea exhibits significant therapeutic efficacy in T1DM mice by improving mitochondrial health and inducing autophagy through the AMPK-mTOR pathway in pancreatic islet β-cells. These findings highlight its potential as a therapeutic approach for T1DM management.

Keywords Animal study · Cai’s herbal tea · Type 1 diabetes mellitus · AMPK-mTOR pathway · Autophagy

Abbreviations

T1DM Type 1 diabetes mellitus

INS Insulin

IL-1β Interleukin-1β

MAP1LC3

AMPK

UPLC-Q/TOF-MS

Microtubule-associated protein 1 light chain 3

AMP-activated protein kinase Ultra performance liquid chromatography-quadrupole/time of flight-mass

spectrometry

IDA Information dependent acquisition

TG Total triglycerides

TC Total cholesterol

ELISA Enzyme-linked immunosorbent assay

INF-γ Interferon gamma

IL-4 Interleukin 4

HE Hematoxylin and eosin

IHC Immunohistochemistry

TEM Transmission electron microscopy

DMEM Dulbecco’s modified eagle medium

HG High-glucose

si-NC SiRNA negative control

si-AMPK SiRNA AMP-activated protein

kinase

MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-di-

phenyltetrazolium bromide

GSIS Glucose stimulated INS secretion

BIS Basal INS secretion

ISI INS secretion index

NOD Non-obese diabetic