1.Application of Recombinant Collagen in Biomedicine
Huan HU ; Hong ZHANG ; Jian WANG ; Li-Wen WANG ; Qian LIU ; Ning-Wen CHENG ; Xin-Yue ZHANG ; Yun-Lan LI
Progress in Biochemistry and Biophysics 2025;52(2):395-416
Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.
2.Effects and mechanism of astilbin on renal injury in chronic renal failure rats
Xiaowei GAO ; Yingying LIU ; Cong HAN ; Shifei HAO
China Pharmacy 2025;36(4):434-439
OBJECTIVE To investigate the effect and potential mechanism of astilbin (AST) on renal injury in chronic renal failure (CRF) rats based on the Jagged-1/Notch-1 signaling pathway. METHODS CRF model was constructed by 5/6 nephrotomy. The successfully modeled rats were randomly separated into Model group, AST low-dose group (AST-L group), AST high-dose group (AST-H group), high-dose of AST+Notch pathway activator (Jagged-1/FC chimerin, referred to as “JFC”) group (AST-H+ JFC group), and control group (CK group) for open surgery without resection was set up, with 10 rats in each group. The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST, respectively; the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC, and the rats in the CK group and Model group were given an equal volume of normal saline, once a day, for 4 weeks. After the last administration, the serum levels of blood urea nitrogen (BUN), serum creatinine (SCr), and the level of 24 h urinary protein (UP) in urine, as well as the serum levels of lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in each group were detected. The morphology and fibrosis of renal tissue were observed. The content of adenosine triphosphate (ATP) and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected. The protein expressions of transforming growth factor- β (TGF- β), hypoxia-inducible factor-1α (HIF-1α), α-smooth muscle actin (α-SMA), cleaved-caspase-3, Jagged-1 and Notch-1 in renal tissue were also observed. RESULTS Compared with CK group, the renal tissue of rats in the Model group was obviously damaged, renal tissue fibrosis was severe; the serum BUN and SCr levels, urine UP level, serum 4 LDH, TNF-α and IL-6 levels, as well as the protein expressions of TGF-β, HIF-1α, α-SMA, cleaved-caspase-3, Jagged-1 and Notch-1 in renal tissue were significantly increased, while the serum IL-10 level, ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased (P<0.05). Compared with Model group, the renal tissue damage and fibrosis in the AST groups were reduced, the serum BUN and SCr levels, urine UP level, serum LDH, TNF-α and IL-6 levels, and the protein expressions of TGF-β, HIF-1α, α-SMA, cleaved-caspase-3, Jagged-1 and Notch-1 were significantly decreased, while the serum IL-10 level, ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased; the changes in the aforementioned indicators in AST- H group were more significant than those in the AST-L group(P<0.05). JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats (P<0.05). CONCLUSIONS AST can reduce inflammation in CRF rats, alleviate renal tissue damage and fibrosis, and improve renal mitochondrial capacity metabolism, possibly by inhibiting the Jagged-1/Notch-1 signaling pathway.
3.Bioinformatic and Mendelian Randomization Analyses of Correlation Between Differentially Expressed Genes and Prognosis of Oral Squamous Cell Carcinoma Patients
Maolin LIU ; Xiaona SONG ; Yaqi LIU ; Shuxuan SHI ; Guohua SONG
Cancer Research on Prevention and Treatment 2025;52(2):133-141
Objective Differentially expressed genes in oral squamous cell carcinoma (OSCC) were subjected to bioinformatic and Mendelian randomization analyses to elucidate their prognostic significance in OSCC. Methods The TCGA database and dataset GSE138206 were used to screen the common differential genes of OSCC, and their relationship was analyzed by using Mendelian randomization. The prognostic value of differential genes was further analyzed by Cox risk regression. The biological function of genes with high prognostic value was further evaluated by single gene differential analysis. Results A total of 147 common differential genes were screened from the two databases. Results of two-sample Mendelian randomization showed that GREM2 was associated with the increased risk of OSCC. In addition, SH3BGRL2 was associated with a decreased risk of OSCC, and DKK1, CCL11, and HOXC6 were considered as independent prognostic markers of OSCC. The predicted results of DKK1 were consistent with the actual results. KEGG enrichment analysis indicated the potential involvement of DKK1 in arachidonic acid and linoleic acid metabolism. Furthermore, DKK1 showed positive correlations with Tgd and Th2 cells, while displaying negative associations with PDC, Cytotoxic cells, Mast cells, CD8 T cells, TFH cells, B cells, T cells, and Th17 cells. Conclusion GREM2 is associated with an increased risk of OSCC. DKK1 is highly expressed in OSCC and associated with poor prognosis, which may be involved in regulating the metabolism of arachidonic acid and linoleic acid and immune cell invasion in OSCC.
4.Distribution pattern of traditional Chinese medicine syndromes and analysis of influencing factors in pancreatic cancer
Zhiyao SHI ; Shiyu WU ; Shaojian REN ; Yichan LIU ; Yijie YIN ; Yu GAO ; Xixing WANG
Journal of Clinical Hepatology 2025;41(3):528-535
ObjectiveTo investigate the influencing factors for traditional Chinese medicine (TCM) syndromes in pancreatic cancer by analyzing 608 cases, and to provide a theoretical reference for TCM syndrome differentiation and standardized treatment of pancreatic cancer. MethodsA total of 608 patients with a pathological or clinical diagnosis of pancreatic cancer who were admitted to Shanxi Institute of Traditional Chinese Medicine, The Affiliated Hospital of Shanxi University of Chinese Medicine, and Shanxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to December 2023 were enrolled, and TCM syndrome differentiation was performed. The chi-square test was used for comparison of categorical data between groups. The clinical data with statistical significance between groups were included in the regression analysis, and the unordered polytomous logistic regression model was used to investigate the influencing factors for the TCM syndrome of pancreatic cancer. ResultsFor the 608 patients with pancreatic cancer, common initial symptoms included abdominal pain (32.40%), abdominal distension (23.85%), fatigue (16.12%), and emaciation (10.03%), and the main clinical symptoms included poor appetite (75.97%), abdominal pain (67.27%), fatigue (61.84%), abdominal distension (57.40%), and emaciation (53.62%). There were significant differences between the patients with different TCM syndromes of pancreatic cancer in sex (χ2=62.823, P<0.001), disease duration (χ2=14.868, P=0.011), clinical stage (χ2=21.006, P<0.001), lymph node metastasis (χ2=2.205, P=0.032), surgery (χ2=38.008, P<0.001), chemotherapy (χ2=21.384, P<0.001), radiotherapy (χ2=17.510, P=0.004), and immunotherapy (χ2=18.573, P=0.002). The logistic regression analysis showed that male sex was a protective factor against Qi and blood deficiency syndrome (odds ratio [OR]=0.081, 95% confidence interval [CI]: 0.031 — 0.213, P<0.001), Qi stagnation and blood stasis syndrome (OR=0.100, 95%CI: 0.041 — 0.247, P<0.001), and syndrome of Yin deficiency with internal heat (OR=0.158, 95%CI: 0.057 — 0.444, P<0.001), while it was a risk factor for the syndrome of damp-heat accumulation (OR=2.378, 95%CI: 1.074 — 5.266, P=0.033); the course of the disease of<1 year was a protective factor against Qi and blood deficiency syndrome (OR=0.167, 95%CI: 0.073 — 0.383, P<0.001), syndrome of spleen-kidney Yang deficiency (OR=0.183, 95%CI: 0.089 — 0.378, P<0.001), and syndrome of Yin deficiency and internal heat (OR=0.164, 95%CI: 0.070 — 0.385, P<0.001); clinical stage Ⅰ/Ⅱ/Ⅲ was a risk factor for damp-heat accumulation (OR=2.793, 95%CI: 1.259 — 6.196, P=0.012) and Qi stagnation and blood stasis syndrome (OR=7.863, 95%CI: 2.808 — 22.020, P<0.001); lymph node metastasis was a risk factor for Qi and blood deficiency syndrome (OR=4.005, 95%CI: 1.477 — 10.861, P=0.006); surgical treatment was a risk factor for Qi and blood deficiency syndrome (OR=4.151, 95%CI: 1.916 — 8.995, P<0.001), syndrome of spleen-kidney yang deficiency (OR=5.352, 95%CI: 2.436 — 11.759, P<0.001), Qi stagnation and blood stasis syndrome (OR=2.334, 95%CI: 1.071 — 5.088, P=0.033), and syndrome of Yin deficiency and internal heat (OR=4.167, 95%CI: 1.789 — 9.707, P<0.001); chemotherapy was a protective factor against damp-heat accumulation (OR=0.188, 95%CI: 0.082 — 0.428, P<0.001); radiotherapy was a risk factor for damp-heat accumulation (OR=2.571, 95%CI: 1.151 — 5.746, P=0.021) and syndrome of Yin deficiency with internal heat (OR=8.384, 95%CI: 3.348 — 20.997, P<0.001); immunotherapy was a risk factor for Qi and blood deficiency syndrome (OR=2.114, 95%CI: 1.021 — 4.379, P=0.044). ConclusionSex, course of the disease, clinical stage, presence or absence of lymph node metastasis, surgery, chemotherapy, radiotherapy, and immunotherapy are the main influencing factors for the TCM syndrome of pancreatic cancer.
5.Rare giant hepatic angiomyolipoma with subcapsular rupture misdiagnosed as hepatocellular carcinoma: A case report
Zhiwei ZHANG ; Feng LIU ; Hezhao ZHANG ; Qinying WANG ; Zhiyong SHI
Journal of Clinical Hepatology 2025;41(3):536-541
Hepatic angiomyolipoma (HAML) is a rare benign mesenchymal tumor frequently observed in middle-aged women. Due to the absence of prominent symptoms in the early stage and the lack of specific imaging findings, the diagnosis of this disease can be challenging, leading to a high rate of misdiagnosis. This article reports a case of giant HAML with subcapsular rupture that was misdiagnosed as hepatocellular carcinoma and introduces the characteristics of the case and its diagnosis and treatment process, in order to provide a reference for the diagnosis and treatment of this type of disease.
6.Influencing factors for the homing ability of mesenchymal stem cells in end-stage liver disease and optimization measures
Journal of Clinical Hepatology 2025;41(3):561-567
Mesenchymal stem cells (MSCs) have emerged as a promising cellular therapy for end-stage liver disease (ESLD) due to their robust self-regenerative, paracrine, and immunomodulatory characteristics, providing new directions for the treatment of advanced liver disease. However, the clinical application of MSCs is significantly limited by the fact that only a small number of MSCs can reach the liver due to massive apoptosis or necrosis during the homing process caused by the influence of the complex microenvironment (inflammation, oxidative stress, and hypoxia) of the injured liver and the fact that a substantial proportion of MSCs become trapped in the pulmonary capillaries following intravenous administration with a lack of sufficient homing receptors or adhesion molecules. Various strategies have been developed to optimize the proliferation, migration, and homing abilities of MSCs, including preconditioning, gene modification, and nanoencapsulation technology. This article elaborates on the influencing factors for the homing ability of MSCs, the strategies to optimize their homing in ESLD, and the mechanism of the homing of MSCs, in order to improve cell transplantation efficiency, promote liver repair and regeneration, and pave the way for the application of MSCs in the treatment of ESLD.
7.Prevalence and influencing factors of work-related musculoskeletal disorders of coal miners in a coal mine group
Xiaolan ZHENG ; Liuquan JIANG ; Ying ZHAO ; Hongxia ZHAO ; Fan YANG ; Qiang LI ; Li LI ; Yingjun CHEN ; Qingsong CHEN ; Gaisheng LIU
Journal of Environmental and Occupational Medicine 2025;42(3):278-285
Background The positive rate of work-related musculoskeletal disorders (WMSDs) among coal mine workers remains high, which seriously affects the quality of life of the workers. Objective To estimate the prevalence of WMSDs among coal miners in Shanxi Province and analyze their influencing factors. Methods From May to December 2023,
8.Effect modification of amino acid levels in association between polycyclic aromatic hydrocarbon exposure and metabolic syndrome: A nested case-control study among coking workers
Jinyu WU ; Jiajun WEI ; Shugang GUO ; Huixia XIONG ; Yong WANG ; Hongyue KONG ; Liuquan JIANG ; Baolong PAN ; Gaisheng LIU ; Fan YANG ; Jisheng NIE ; Jin YANG
Journal of Environmental and Occupational Medicine 2025;42(3):325-333
Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnvOHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P50), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P75) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.
9.Association between lifestyle and cardiovascular-metabolic risk factor aggregation in a young and middle-aged male occupational population
Baoyi LIANG ; Lyurong LI ; Yingjun CHEN ; Lingxiang XIE ; Gaisheng LIU ; Liuquan JIANG ; Lu YU ; Qingsong CHEN
Journal of Environmental and Occupational Medicine 2025;42(4):385-391
Background Unhealthy lifestyle behaviors may be associated with an increased risk of cardiometabolic risk factor aggregation (CMRF≥ 2), and few studies have focused on the correlation between the two in occupational populations. Objective To investigate the current status of CMRF≥2 and the compliance of healthy lifestyle in male occupational personnel, explore the effect of lifestyle on cardiometabolic risk, and provide reference for formulating healthy behavior promotion strategies and reducing cardiometabolic risk in occupational populations. Methods The study subjects were selected from male workers who completed occupational health examinations at an occupational disease prevention and control hospital in Shanxi Province from May to December 2023, and
10.Impact of shift work and obesity on risk of hyperuricemia in coal miners: A cross-sectional design based dose-response relationships and interaction analysis
Zeyuan ZHANG ; Yingjun CHEN ; Yingtong CHEN ; Mengtian XIONG ; Zichao PANG ; Gaisheng LIU ; Hongxia ZHAO ; Liuquan JIANG ; Qingsong CHEN
Journal of Environmental and Occupational Medicine 2025;42(4):451-458
Background The prevalence of hyperuricemia (HUA) among Chinese residents has been increasing annually, with occupational populations facing a higher risk of HUA due to shift work or obesity. Objective To investigate the impact of shift work and obesity on HUA among coal miners, and to provide scientific data for the prevention of HUA in this occupational group. Methods A cross-sectional study was conducted with

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