1.Research progress on natural active ingredients intervening in the hypoxia-pyroptosis-inflammation cascade in intervertebral disc degeneration through HIF-1α
Hao WANG ; Renchang CHEN ; Wenhao HUANG ; Bingqian ZHOU ; Xiqiu ZHENG ; Jiahao WANG ; Nianhu LI ; Yadong WU
China Pharmacy 2026;37(8):1092-1098
Intervertebral disc degeneration (IVDD) is the core cause of chronic low back pain, which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α (HIF-1α) is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine (TCM) have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects, favorable efficacy, and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein, curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression: targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade, inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals, intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity, and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.
2.Staged Characteristics of Mitochondrial Energy Metabolism in Chronic Heart Failure with Heart-Yang Deficiency Syndrome and Prescription Intervention from Theory of Reinforcing Yang
Zizheng WU ; Xing CHEN ; Lichong MENG ; Yao ZHANG ; Peng LUO ; Jiahao YE ; Kun LIAN ; Siyuan HU ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):129-138
Chronic heart failure (CHF) is a complex clinical syndrome caused by ventricular dysfunction, with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome, as the core pathogenesis of CHF, persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions, resulting in the accumulation of phlegm-fluid, blood stasis, and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention, forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang, the clinical experience of the traditional Chinese medicine (TCM) master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome, and achievements from molecular biological studies, this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild (Stage Ⅰ-Ⅱ), severe (Stage Ⅲ), and critical (Stage Ⅳ) stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical, pathophysiological, and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance, corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α(PGC-1α)/silent information regulator 2 homolog 1 (SIRT1) and ATPase activity. The severe stage centers on oxidative stress and structural damage, reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage, Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage, increase adenosine triphosphate (ATP) content, and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration, leading to the collapse of Yin-Yang equilibrium. At this stage, Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore (MPTP), reduce cardiomyocyte apoptosis rate, and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF, this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.
3.Danhong Injection Regulates Ventricular Remodeling in Rat Model of Chronic Heart Failure with Heart-Blood Stasis Syndrome via p38 MAPK/NF-κB Signaling Pathway
Zizheng WU ; Xing CHEN ; Jiahao YE ; Lichong MENG ; Yao ZHANG ; Junyu ZHANG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):149-159
ObjectiveTo explore the mechanism of ventricular remodeling mediated by the p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signaling pathway in the rat model of chronic heart failure (CHF) with heart-blood stasis syndrome, as well as the intervention effect of Danhong injection. MethodsIn vivo experiment: SPF-grade male SD rats were assigned via the random number table method into 4 groups: Sham operation, model, captopril (8.8 mg·kg-1), and Danhong injection (6.0 mL·kg-1). The model of CHF with heart-blood stasis syndrome was established by abdominal aortic constriction, and the sham operation group only underwent laparotomy without constriction. All the groups were treated continuously for 15 days. The tongue color of rats was observed. Echocardiography, hemorheology, heart mass index (HMI), and left ventricular mass index (LVMI) were measured. Hematoxylin-eosin (HE) staining and Masson staining were performed to observe the pathological and fibrotic changes of the myocardial tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), angiotensin Ⅱ (AngⅡ), tumor necrosis factor-α (TNF-α), and Creactive protein (CRP) in the serum, as well as the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the myocardial tissue. Western blot was used to quantify the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue. In vitro experiment: H9C2 cardiomyocytes were treated with 1×10-6 mol·L-1 AngⅡ to establish a model of myocardial hypertrophy. H9C2 cardiomyocytes were allocated into normal, model, inhibitor + Danhong injection, Danhong injection (20 mL·L-1), and inhibitor (SB203580, 5 μmol·L-1) groups. CCK-8 assay was used to detect the viability of H9C2 cardiomyocytes. Rhodamine-labeled phalloidin staining was used to reveal the area of cardiomyocytes. Real-time PCR was performed to determine the mRNA levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Western blot was used to assess the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65. ResultsIn vivo experiment: Compared with the sham operation group, the model group showed purplish-dark tongue with decreased R, G, B values of the tongue surface (P<0.01), increased whole blood viscosity (at low, medium, and high shear rates) (P<0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01), increased left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), and left ventricular posterior wall thickness at end-diastole (LVPWd) (P<0.01), raised LVMI and HMI (P<0.01), and elevated levels of NT-proBNP, TNF-α, IL-6, and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue (P<0.01). The HE and Masson staining of the myocardial tissue showed compensatory myocardial hypertrophy, fibrosis, and massive inflammatory cell infiltration in the model group. Additionally, the model group presented up-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue (P<0.01). Compared with the model group, each administration group showed increased R, G, B values of the tongue surface (P<0.05, P<0.01), decreased whole blood viscosity (at low, medium, and high shear rates) (P<0.05, P<0.01), increased LVEF and LVFS (P<0.01), decreased LVIDd, LVIDs, and LVPWd (P<0.05, P<0.01), declined LVMI and HMI (P<0.05, P<0.01), and lowered levels of NT-proBNP, TNF-α, IL-6, and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue (P<0.01). HE and Masson staining showed alleviated compensatory myocardial hypertrophy, reduced fibrosis, and decreased expression of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue (P<0.01). In vitro experiment: When the concentration of Danhong injection reached 20 mL·L-1, the survival rate of H9C2 cardiomyocytes was the highest (P<0.01). Compared with the normal group, the model group showed up-regulated mRNA levels of ANP and BNP (P<0.01), increased relative cell surface area (P<0.01), and raised protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 (P<0.01). Compared with the model group, each administration group showed down-regulated mRNA levels of ANP and BNP (P<0.01), reduced relative cell surface area (P<0.05, P<0.01), and down-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 (P<0.05, P<0.01). ConclusionDanhong injection can regulate ventricular remodeling through the p38 MAPK/NF-κB pathway, thereby exerting a protective effect on the rat model of CHF with heart-blood stasis syndrome.
4.Correlation Analysis Between Microbial Community Changes and Medicinal Quality Formation During Processing of Angelicae Dahuricae Radix
Xiaoyan CHEN ; Xinglong ZHU ; Qingxia GAN ; Jiahao WANG ; Guangqin AN ; Qinghua WU ; Jin PEI ; Yuntong MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):198-207
ObjectiveTo compare the differences in color, odor, coumarin content and microbial community composition of Angelicae Dahuricae Radix(ADR) during different drying processes, and to explore the correlation between changes in microbial community composition and changes in quality indexes of ADR. MethodsThe fresh ADR was processed at three drying temperatures(50, 70, 100 ℃) by drying and steaming cutting, semi-fresh cutting and drying, fresh cutting and drying, and sulfur fumigation methods. The color values of samples were extracted by Adobe Photoshop 2022 software and subjected to principal component analysis(PCA), electronic nose was used to identify the odor information of medicinal powders and subjected to loadings analysis, PCA, and linear discriminant analysis(LDA), and high performance liquid chromatography(HPLC) was used to determine the contents of five coumarins(bergapten, oxypeucedanin, imperatorin, phellopterin, isoimperatorin). The samples for microbial detection were taken from fresh dried samples, 50 ℃(dried and steamed cut, sulfur fumigated) samples, and 100 ℃(dried and steamed cut) samples when the water content was 50% and 14%, respectively. And the changes of microbial community composition during processing were determined by high-throughput sequencing method. The relationship between the changes of microbial community composition and the changes of odor, color and active component content of ADR during drying process was analyzed by Pearson correlation analysis. ResultsThe color quantification results showed that an increase in drying temperature led to the decrease of brightness value(L), and the increases of red-green value(a) and yellow-blue value(b), and the change of processing method had no obvious effect on the color of medicinal materials. The results of odor quantification showed that W1S, W2S, W5S, W2W and W1W sensor were sensitive to the odor changes of ADR and could be used to distinguish ADR decoction pieces from different processing methods. The results of HPLC showed that the coumarin content of ADR decreased with the increase of drying temperature and the delay of processing time, the optimal processing method was drying and steaming cutting method, and the optimal temperature was 50 ℃. High-throughput sequencing results showed that the dominant bacteria in ADR during processing were Achromobacter, Agrobacterium, Nocardioides, Mycobacterium and Enterobacter, the dominant fungi were Coprinopsis, Meyerozyma and Apiotrichum. The results of correlation analysis showed that the quality indexes of ADR were positively correlated with Agrobacterium, Mycobacterium in bacteria, Candida in fungi, and negatively correlated with Bacillus in bacteria. ConclusionThere are significant differences in the color, odor, coumarin content and microbial community composition of ADR in different drying processes, and the best drying method is drying and steaming cutting at 50 ℃. The relative abundance changes of 9 bacterial genera and 4 fungal genera are closely related to the quality formation of ADR during the drying process.
5.Combination of effective ingredients of traditional Chinese medicine and bone tissue engineering materials for bone repair
Yaokun WU ; Chenglin LIU ; Jiahao FU ; Wei SONG ; Hao CHEN ; Hongzhong XI ; Xin LIU ; Bin DU ; Guangquan SUN
Chinese Journal of Tissue Engineering Research 2025;29(10):2141-2150
BACKGROUND:How to repair bone defect has been a clinical problem for a long time.The effective ingredients of traditional Chinese medicine have good biological activity and therapeutic effect,and the combination of effective ingredients of traditional Chinese medicine and tissue engineering materials has a broad prospect in the field of bone repair.The combination of different effective ingredients of traditional Chinese medicine and scaffolds has similarities in their functional relationships. OBJECTIVE:To collect the cases of the combinations of effective ingredients of traditional Chinese medicine and scaffolds,then analogize tissue engineering scaffolds and effective ingredients of traditional Chinese medicine into two types of traditional Chinese medicine that generate compatibility relationships based on the inspiration of the compatibility of seven emotions and summarize the relationship between the two based on their functional relationships. METHODS:Relevant articles from January 1998 to January 2024 were searched in PubMed and China National Knowledge Infrastructure(CNKI),using English search terms"traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold"and Chinese search terms"traditional Chinese medicine,effective ingredients of traditional Chinese medicine,traditional Chinese medicine monomers,bone tissue engineering,bone tissue engineering scaffold,scaffold,tissue engineering,bone defect,bone repair."A total of 88 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Both tissue engineering scaffold materials and active ingredients of traditional Chinese medicine have been widely used in the field of bone repair.Although they have obvious advantages in osteogenesis,there are still many shortcomings.Many studies are dedicated to preparing composite materials from the two,hoping to exert a detoxification and synergism through the interaction between the two.(2)Some drugs and materials can promote each other in osteogenesis,antibacterial,and promoting angiogenesis,enhancing their original effects.Inspired by the traditional concept of prescription compatibility,this article summarized it as a"Mutual promotion"relationship and provided examples to support it.(3)Some drugs can enhance the strength of materials,while some materials can achieve sustained release and controlled release effects,increase drug loading and stability,or achieve targeted delivery of drugs loaded on them.The article summarized this unilateral enhancement effect as a"Mutual assistance"relationship.(4)The combination of some traditional Chinese medicine and materials can reduce the toxic side effects of the other party.The article summarizes this detoxification relationship as"Mutual restraint and detoxification."(5)The article provided a new perspective on traditional Chinese medicine composite scaffolds,inspired by the seven emotions compatibility relationship and based on the classification of action relationships.It introduced traditional Chinese medicine concepts into the field of tissue engineering,providing new research ideas for subsequent researchers of composite scaffolds,and providing certain convenience in material selection and matching.
6.Recent advances in roles and mechanisms of adenosine,adenosine receptors,and adenosine derivatives in pulmonary diseases
Binglu QIAN ; Cheng YUAN ; Mingrui LIU ; Jiahao DONG ; Hao WU ; Yingjiao LIU
Chinese Journal of Pharmacology and Toxicology 2025;39(10):790-798
Adenosine,as a purine nucleoside widely present in living organisms,plays an impor-tant role in such physiological and pathological processes as vasodilation,inflammation regulation,fibrosis,and viral infection.Research has found that in pulmonary hypertension,adenosine acts as a vasodilator through multiple targets.In diseases such as mycoplasma pneumonia,asthma,chronic obstructive pulmonary disease,and idiopathic pulmonary fibrosis,adenosine primarily mediates the progression of inflammation through interactions with adenosine A2A and A2B receptors,thus delivering a dual regulatory effect.This suggests that modulating adenosine receptors is a potential key target for the treatment of pulmonary diseases.Adenosine derivatives-such as acyclovir monophosphate,which has antiviral effects,cyclic adenosine monophosphate,which can alleviate airway narrowing,and N-6-methyladenosine,which is involved in regulating cilia homeostasis and anti-pulmonary fibrosis-are closely related to the occurrence and development of pulmonary diseases.Targeting the adenosine A2A receptor or antagonizing the adenosine A2B receptor can precisely intervene in specific pulmo-nary diseases.Combination medications,regulation of adenosine metabolic pathways,and gene editing technologies promise new treatments.This article reviews the role of adenosine,its receptors,and derivatives in the development of pulmonary diseases in the hopes of providing evidence for related treatment.
7.Experience in diagnosis and treatment of acute Stanford type A aortic dissection involving coronary arteries
Jie CHEN ; JiaHao PAN ; Cong NIE ; Xiaolong MA ; Jiawen LUO ; Fei CHEN ; Ming WU ; Anxing HOU ; Qing ZHOU ; Wenwu ZHOU
Journal of Chinese Physician 2025;27(8):1130-1134
Objective:To analyze the anatomical characteristics and surgical management measures of acute Stanford type A aortic dissection (AAD) involving coronary arteries, and to preliminarily explore the clinical efficacy of different coronary artery treatment techniques.Methods:A retrospective analysis was conducted on the clinical data of 42 patients who underwent surgery for AAD involving coronary arteries in Hunan Provincial People′s Hospital from January 2022 to May 2025. They were divided into the MI group (14 cases) and the nMI group (28 cases) according to whether they had acute myocardial infarction before surgery. The clinical data such as the actual surgical methods and mortality in the two groups were summarized.Results:Among 294 surgeries, 42 cases (14.3%) had definite coronary artery involvement, including 14 cases in the MI group and 28 cases in the nMI group; 1 case had bilateral coronary artery involvement and 41 cases had right coronary artery involvement. Regarding injury types: 16 cases were of the coronary trunk compression type, 12 cases were of the sinus intimal tear neal to ostium type, and 14 cases were of the coronary trunk intimal type. There was no statistically significant difference in the types of coronary artery involvement between the two groups ( P>0.05). There were 18 cases of Sun′s procedure with preserved aortic sinus and aortic valve, 7 cases of Bentall procedure without bypass, and 17 cases of Bentall procedure plus bypass. There was no statistically significant difference in the surgical plans between the two groups ( P>0.05). There were 4 deaths within 30 days (2 cases in each group). Conclusions:AAD involving coronary arteries is a critical condition, and accurate diagnosis is somewhat difficult. Myocardial ischemia is not significantly associated with the type of coronary artery involvement. The surgical plan depends on the type of coronary artery involvement. The classification method in this study is conducive to selecting appropriate surgical methods and improving surgical prognosis.
8.Clinical characteristics and outcomes of elderly patients with stage Ⅰ diffuse large B-cell lymphoma: a study by the Jiangsu Cooperative Lymphoma Group (JCLG)
Yi XIA ; Jing HE ; Weiying GU ; Tao JIA ; Tingxun LU ; Yongle LI ; Jiahao ZHOU ; Bingzong LI ; Haiying HUA ; Ping LIU ; Yuqing MIAO ; Yuexin CHENG ; Xiaoyan XIE ; Yunping ZHANG ; Wenzhong WU ; Zhuxia JIA ; Xuzhang LU ; Chunling WANG ; Liang YU ; Min XU ; Jinning SHI ; Weifeng CHEN ; Wanchuan ZHUANG ; Zhen QIAN ; Jun QIAN ; Haiwen NI ; Yifei CHEN ; Qiudan SHEN ; Jianyong LI ; Wenyu SHI
Chinese Journal of Internal Medicine 2025;64(6):504-513
Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.
9.Association between physical activity and cognitive impairment in older adults aged 65 years and above in longevity areas of China
Hang XU ; Yudong WU ; Chen CHEN ; Xi MENG ; Jiahao CHEN ; Zenghang ZHANG ; Zhuchun ZHONG ; Jingjing YANG ; Xiaoshuang FU ; Sirui CHEN ; Yongqiang CHEN ; Zhipei LI ; Lin YE ; Xiaoming SHI ; Yuebin LYU
Chinese Journal of Epidemiology 2025;46(5):753-760
Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.
10.Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate aging in mice.
Sipeng WU ; Yiqi CAI ; Lixiao ZHANG ; Xiang LI ; Xu LIU ; Guangkeng ZHOU ; Hongdi LUO ; Renjian LI ; Yujia HUO ; Zhirong ZHANG ; Siyi CHEN ; Jinliang HUANG ; Jiahao SHI ; Shanwei DING ; Zhe SUN ; Zizhuo ZHOU ; Pengcheng WANG ; Geng WANG
Protein & Cell 2025;16(1):28-48
One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals
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Mice
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RNA, Untranslated/metabolism*
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Aging/genetics*
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Mice, Transgenic
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Telomerase/metabolism*
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RNA/genetics*
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Hippocampus/metabolism*
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Humans
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Mice, Inbred C57BL

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