1.PDGF-C: an Emerging Target in The Treatment of Organ Fibrosis
Chao YANG ; Zi-Yi SONG ; Chang-Xin WANG ; Yuan-Yuan KUANG ; Yi-Jing CHENG ; Ke-Xin REN ; Xue LI ; Yan LIN
Progress in Biochemistry and Biophysics 2025;52(5):1059-1069
Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.
2.Research progress on the regulation of diabetic retinopathy by the mTOR-autophagy pathway
Tingting QIN ; Leying ZHANG ; Ting LI ; Xiaohui KUANG ; Jiaojiao WANG ; Zongming SONG
International Eye Science 2025;25(10):1617-1622
Diabetic retinopathy(DR)is one of the most common and severe microvascular complications in diabetic patients and has become one of the leading causes of blindness worldwide. With the continuous rise in the prevalence of diabetes, in-depth exploration of the pathogenesis of DR and effective intervention measures is of great clinical significance. The mechanistic target of rapamycin(mTOR), as a protein kinase, is widely involved in cellular processes such as growth, metabolism, and autophagy. Research indicates that the mTOR signaling pathway plays a crucial regulatory role in the pathological progression of DR, and its abnormal activity can disrupt retinal cell autophagy function, thereby accelerating cellular damage and disease progression. Autophagy, as an important regulatory mechanism for cellular homeostasis, maintains cellular functional balance by clearing damaged organelles and protein aggregates. This article provides a systematic review of the structural and functional aspects of the mTOR signaling pathway, the molecular regulatory mechanisms of autophagy, and their roles in retinal pathological changes. By summarizing current research findings, the article aims to clarify the key regulatory role of the mTOR-autophagy axis in DR, providing theoretical support for elucidating the molecular pathogenesis of DR and offering potential targets and research directions for developing novel targeted therapeutic strategies, thereby holding significant scientific and clinical value.
3.Latest advances in clinical management of advanced primary open angle glaucoma
International Eye Science 2025;25(12):1958-1964
Primary open angle glaucoma(POAG)is a chronic, progressive optic neuropathy characterized by pathologically elevated intraocular pressure(IOP), which is the main high-risk factor, although the etiology is still unclear. Due to the insidious onset, many patients are already in the intermediate or advanced stages at the first presentation. At these stages, optic nerve damage is often severe, the target IOP requirement is stringent(below 12 mmHg), with poor tolerance to treatment, which necessitates comprehensive treatment approaches to control disease progression. This review systematically summarizes recent advances in the clinical management of advanced POAG, including medications, laser therapy, trabeculectomy, glaucoma drainage device implantation, minimally invasive glaucoma surgery and other emerging therapies. It elaborates on the mechanisms of action, efficacy, safety, suitable populations, and indications for switching treatments. Incorporating the latest clinical research data up to 2025, the analysis evaluates the impact of different treatment approaches on clinical practice and explores the future development trends, aiming to provide comprehensive references for individualized treatment strategies to maximize preservation of visual function in patients with advanced POAG.
4.History and Clinical Application of Classic Famous Formula Danggui Sinitang
Sihong LIU ; Siqi JIA ; Lin TONG ; Li REN ; Lei ZHANG ; Lei YANG ; Yanhui KUANG ; Deqin WANG ; Bing LI ; Huamin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):53-60
Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Asari Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Tetrapanacis Medulla, and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition, plant species, processing, dosage, decocting method, and indications of Danggui Sinitang, aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition, and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties, the medical practitioners continued to use the original formula. In terms of processing, although there were slight changes in the processing of Angelicae Sinensis Radix, Paeoniae Radix Alba, Glycyrrhizae Radix et Rhizoma, and Tetrapanacis Medulla, the original processing method was inherited. In terms of indications, Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore, it was used to treat headache, convulsive disease, infantile convulsion, and private part adduction in the Ming and Qing dynasties. Nowadays, this formula is mostly used to treat diabetes peripheral neuropathy, rheumatoid arthritis, dysmenorrhea, Raynaud's disease and other diseases. In terms of precautions, ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons, this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development, quality control standards of Danggui Sinitang should be established while its safety is ensured, and the related preparations should be developed and applied.
5.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
6.Analysis of clinical characteristics of 33 cases of tuberculosis complicated by tumor necrosis factor-α inhibi-tor in autoimmune diseases
Yigang TAN ; Haobin KUANG ; Hongmei FU ; Chunyan LI ; Xiaobing ZHAO ; Lijing XUE
The Journal of Practical Medicine 2024;40(3):378-383
Objective To investigate the clinical characteristics,treatment and prognosis of tuberculosis in patients with autoimmune diseases after tumor necrosis factor-αinhibitors.Methods Clinical data of 33 patients with TB after biologics(tumor necrosis factor-α inhibitors)treated in Guangzhou Chest Hospital from January 2019 to March 2023 were collected,including 25 males and 8 females,with a median age of 32 years.The clinical symptoms,laboratory results,imaging and tracheoscopic features,pathological features,treatment and outcome were analyzed retrospectively.Results The common clinical manifestations were cough(26/33),sputum(23/33)and fever(17/33).The most common cases were pulmonary tuberculosis(32/33),bronchial tuberculosis(15/33),mediastinum and hilar lymph node tuberculosis(11/33).Bilateral lung spread of tuberculosis(21/33),intrapulmonary spread of tuberculosis(bronchus,mediastinal hilar lymph nodes,pleura)(19/33),extrapulmonary tuberculosis(18/33),pulmonary tuberculosis with intrapulmonary or extrapulmonary tuberculosis(26/33).Blood CD4+T lymphocyte test was normal(23/33),and blood IGRA test was positive(27/33).Pulmonary imaging miliary nodules(8/33).The histopathology of the lymph nodes showed atypical granulomatous nodules.The duration of anti-tuberculosis treatment is 8-32 months.1 case of death.Conclusion Patients with autoimmune diseases complicated with tuberculosis after the application of tumor necrosis fact-α inhibitor are more likely to have double lung lesions,which are easy to spread to lung tissues and multiple organs of the body,and have decreased immune function.Most of them need to extend the treatment course,and the prognosis is generally good after comprehensive treatment.
7.Accuracy evaluation of bioelectrical impedance analysis in assessment of appendicular skeletal muscle mass in adults aged 18-42 years
Yiying ZHENG ; Hong CHENG ; Yuxian KUANG ; Zhenxin MA ; Weiye CHEN ; Keyuan LU ; Jie MI ; Li LIU
The Journal of Practical Medicine 2024;40(4):549-553
Objective To evaluate the accuracy of bioelectrical impedance analysis(BIA)in measurement of appendicular skeletal muscle mass(ASM)of adults.Methods A total of 836 adults aged 18-42 years were recruited in Guangzhou using a convenient sampling method from April 2021 to September 2022.ASM was measured using BIA and Dual-energy X-ray absorptiometry(DXA).Using DXA as the standard method,the consistency between the BIA and DXA measurements was evaluated by intra-class correlation coefficients(ICCs)and Bland-Altman analysis in logarithmically transformed data,in order to evaluate the accuracy of BIA in ASM measurement.Receiver operating characteristic curve was plotted to evaluate the diagnostic value of BIA for screening low muscle mass.Results A total of 774 individuals were included for analysis finally.ICCs for ASM measured by BIA and DXA were 0.774 and 0.667 in males and females,respectively.Mean ratios(limits of Agreement)of ASM were 0.94(0.80-1.10)and 0.91(0.78-1.05)in males and females,respectively.Area under curve of BIA for screening low muscle mass were 0.91 and 0.94 in males and females,respectively.The optimal cut-off values of Z-score by BIA for males and females were-0.57 and-0.66,respectively.Sensitivity and specificity for males were 82.5%and 86.0%,while being 86.8%and 93.8%,for females.Conclusion BIA shows a moderate consistency with DXA for measuring ASM in adults.Furthermore,BIA yields a good diagnostic value in identifying low muscle mass in adults aged 18-42 years.
8.Clinical safety and validity analysis of retrograde new endo-scopic visual field in miniature pigs
Zhe KUANG ; Peng LI ; Da-Qing JIN ; Yong-Chao ZHANG ; Hui-Li GUO ; Yu-Fei ZHANG ; Guang-Lin HE ; Guo-Feng SUN ; Yuan HE
Chinese Journal of Current Advances in General Surgery 2024;27(1):14-18
Objective:To study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.
9.Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway
Qi QI ; Liang OU ; Weichen HUANG ; Zehua CHEN ; Daoqing XU ; Weiwei HU ; Jingjing LI ; Jianjun KUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):29-36
ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway of rabbits with knee osteoarthritis (KOA) and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups (n=6): sham group, model group, low-dose and high-dose groups of Tongluo Juanbi granules (4.1 and 8.2 g·kg-1·d-1), and celecoxib group (10.9 mg·kg-1·d-1). The KOA model was established by destabilization of the medial meniscus (DMM) for six weeks. Six weeks after the modeling, the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultCompared with the sham group, the cartilago articularis of the model group significantly degenerated. Mankin's score was increased (P<0.01), and the contents of IL-1β and TNF-α in synovial fluid were increased (P<0.01). The number of apoptosis of chondrocytes was increased (P<0.01). The mRNA and protein expressions of TLR4, MyD88, and NF-κB p65 in cartilage tissue were up-regulated (P<0.01), while the mRNA and protein expressions of Bcl-2 were down-regulated (P<0.01). Compared with the model group, chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved, and Mankin's score was decreased (P<0.01). The contents of IL-1β and TNF-α were decreased (P<0.01), and the number of apoptosis of chondrocytes was decreased (P<0.01). The mRNA and protein expressions of TLR4, MyD88, and NF-κB p65 in cartilage tissue were down-regulated (P<0.01), while the mRNA and protein expressions of Bcl-2 were up-regulated (P<0.01). In addition, in the above observation indicators, the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration, which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.
10.Advances in crystal nucleation for amorphous drugs
Jie ZHANG ; Kang LI ; Zi-qing YANG ; Zi-han DING ; Sai-jun XIAO ; Zhi-ming YUE ; Li-mei CAI ; Jia-wen LI ; Ding KUANG ; Min-zhuo LIU ; Zhi-hong ZENG
Acta Pharmaceutica Sinica 2024;59(7):1962-1969
Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

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