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.Exploration of pharmacodynamic material basis and mechanism of Jinbei Oral Liquid against idiopathic pulmonary fibrosis based on UHPLC-Q-TOF-MS/MS and network pharmacology.
Jin-Chun LEI ; Si-Tong ZHANG ; Xian-Run HU ; Wen-Kang LIU ; Xue-Mei CHENG ; Xiao-Jun WU ; Wan-Sheng CHEN ; Man-Lin LI ; Chang-Hong WANG
China Journal of Chinese Materia Medica 2025;50(10):2825-2840
This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics*
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Animals
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Tandem Mass Spectrometry
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Network Pharmacology
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Rats
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Chromatography, High Pressure Liquid
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Rats, Sprague-Dawley
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Male
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Idiopathic Pulmonary Fibrosis/metabolism*
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Humans
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Administration, Oral
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Protein Interaction Maps/drug effects*
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Signal Transduction/drug effects*
3.Optimal harvesting period of cultivated Notopterygium incisum based on HPLC specific chromatogram combined with chemometrics and entropy weight-gray correlation analysis.
Jing-Cheng WANG ; Hong-Bing SUN ; Teng LIU ; Wen-Tao ZHU ; Hong-Lan WANG ; Yi ZHOU ; Wei-Yan WANG ; Ping YANG ; Shun-Yuan JIANG
China Journal of Chinese Materia Medica 2025;50(14):3878-3886
To determine the optimal cultivation duration and harvest period for cultivated Notopterygium incisum and promote its industrial development, this study established a characteristic chromatographic profile of cultivated N. incisum and employed chemometrics combined with entropy-weighted grey correlation analysis to assess differences in agronomic traits and quality indicators across different cultivation years and harvest periods. By comparing with reference substances, ten common peaks were identified, including chlorogenic acid, p-coumaric acid, ferulic acid, marmesinin, nodakenin, isochlorogenic acid B, notopterol, phenethyl ferulate, isoimperatorin, and falcarindiol. The similarity between the characteristic chromatographic profiles of N. incisum at different cultivation years and the reference profile was all above 0.932. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) revealed that the quality of 1-to 3-year-old cultivated N. incisum was highly dispersed and unstable, whereas the quality of 4-year-old cultivated N. incisum remained relatively stable across different harvest periods. This suggests that the accumulation of relevant compounds in the medicinal material had reached a plateau, confirming that the optimal cultivation period for N. incisum is four years. Entropy-weighted grey correlation analysis indicated that the quality of 4-year-old cultivated N. incisum across different harvest periods ranked from highest to lowest as follows: November, December, October, August, July, and September, demonstrating that November is the optimal harvest time. The findings of this study establish the suitable cultivation duration and optimal harvest period for N. incisum, providing a scientific basis for cultivation guidance and quality standardization.
Chromatography, High Pressure Liquid/methods*
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Apiaceae/chemistry*
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Entropy
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Chemometrics/methods*
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Drugs, Chinese Herbal/chemistry*
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Principal Component Analysis
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Quality Control
4.Microdissection testicular sperm extraction for men with nonobstructive azoospermia who have a testicular tumor in situ at the time of sperm retrieval.
Hao-Cheng LIN ; Wen-Hao TANG ; Yan CHEN ; Yang-Yi FANG ; Kai HONG
Asian Journal of Andrology 2025;27(3):423-427
Oncological microdissection testicular sperm extraction (onco-micro-TESE) represents a significant breakthrough for patients with nonobstructive azoospermia (NOA) and a concomitant in situ testicular tumor, to be managed at the time of sperm retrieval. Onco-micro-TESE addresses the dual objectives of treating both infertility and the testicular tumor simultaneously. The technique is intricate, necessitating a comprehensive understanding of testicular anatomy, physiology, tumor biology, and advanced microsurgical methods. It aims to carefully extract viable spermatozoa while minimizing the risk of tumor dissemination. This review encapsulates the procedural intricacies, evaluates success determinants, including tumor pathology and spermatogenic tissue health, and discusses the implementation of imaging techniques for enhanced surgical precision. Ethical considerations are paramount, as the procedure implicates complex decision-making that weighs the potential oncological risks against the profound desire for fatherhood using the male gametes. The review aims to provide a holistic overview of onco-micro-TESE, detailing methodological advances, clinical outcomes, and the ethical landscape, thus offering an indispensable resource for clinicians navigating this multifaceted clinical scenario.
Humans
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Male
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Azoospermia/therapy*
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Testicular Neoplasms/pathology*
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Sperm Retrieval
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Microdissection/methods*
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Testis/surgery*
5.Sequential therapy with carglumic acid in three cases of organic acidemia crisis.
Yan-Yan CHEN ; Ting-Ting CHENG ; Jie YAO ; Long-Guang HUANG ; Xiu-Zhen LI ; Wen ZHANG ; Hong LIANG
Chinese Journal of Contemporary Pediatrics 2025;27(7):850-853
Case 1: A 19-day-old male infant presented with poor feeding and decreased activity for 2 weeks, worsening with poor responsiveness for 3 days. At 5 days old, he developed poor feeding and poor responsiveness, was hospitalized, and was found to have elevated blood ammonia and thrombocytopenia. Whole-genome genetic analysis revealed a pathogenic homozygous mutation in the PCCA gene, NM-000282.4: c.1834-1835del (p.Arg612AspfsTer44), leading to a diagnosis of propionic acidemia. Case 2: A 4-day-old male infant presented with poor responsiveness and feeding difficulties since birth, with elevated blood ammonia for 1 day. He showed weak sucking and deteriorating responsiveness, with blood ammonia >200 µmol/L. Genetic testing identified two heterozygous mutations in the MMUT gene: NM_000255.4: c.1677-1G>A and NM_000255.4: ex.5del, confirming methylmalonic acidemia. Case 3: A 20-day-old male infant presented with poor feeding for 15 days and skin petechiae for 8 days. He developed feeding difficulties at 5 days old and lower limb petechiae at 12 days old, with blood ammonia measured at 551.6 µmol/L. Genetic analysis found two heterozygous mutations in the PCCA gene: NM_000282.4: c.1118T>A (p.Met373Lys) and NM_000282.4: ex.16-18del, confirming propionic acidemia. In the first two cases, continuous hemodiafiltration was performed for 30 hours and 20 hours, respectively, before administering carglumic acid. In the third case, carglumic acid was administered orally without continuous hemodiafiltration, resulting in a decrease in blood ammonia from 551.6 µmol/L to 72.0 µmol/L within 6 hours, with a reduction rate of approximately 20-25 µmol/(kg·h), similar to the first two cases. Carglumic acid was effective in all three cases, suggesting it may help optimize future treatment protocols for organic acidemia.
Humans
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Male
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Infant, Newborn
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Propionic Acidemia/drug therapy*
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Amino Acid Metabolism, Inborn Errors/genetics*
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Mutation
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Methylmalonyl-CoA Decarboxylase/genetics*
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Citrates/administration & dosage*
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Carbon-Carbon Ligases/genetics*
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Glutamates
6.Association between ABO Blood Types and the Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.
Shuang Hua XIE ; Shuang Ying LI ; Shao Fei SU ; En Jie ZHANG ; Shen GAO ; Yue ZHANG ; Jian Hui LIU ; Min Hui HU ; Rui Xia LIU ; Wen Tao YUE ; Cheng Hong YIN
Biomedical and Environmental Sciences 2025;38(6):678-692
OBJECTIVE:
To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk.
METHODS:
A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk.
RESULTS:
A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses.
CONCLUSION
The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans
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Female
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Pregnancy
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Diabetes, Gestational/etiology*
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ABO Blood-Group System
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Adult
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Prospective Studies
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Risk Factors
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Young Adult
7.Clinical Efficacy of Bushen Tongmai Prescription in Treating Type 2 Diabetes Mellitus Complicated with Atherosclerotic Cardiovascular Disease of Kidney Deficiency and Blood Stasis Type and Its Influence on Serum Mir-126
Yilan HU ; Xiaodan SONG ; Miaoyu WEN ; Luyi LUO ; Hong CHENG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(4):842-848
Objective To observe the clinical efficacy of Bushen Tongmai Prescription in treating type 2 diabetes mellitus(T2DM)complicated with atherosclerotic cardiovascular disease(ASCVD)of kidney deficiency and blood stasis type,and to investigate its effect on serum microRNA-126(miR-126).Methods Sixty patients with T2DM complicated with ASCVD of kidney deficiency and blood stasis type who admitted to the outpatient and inpatient departments of the Department of Geriatric Medicine of Shenzhen Traditional Chinese Medicine Hospital from March 2023 to October 2023 were randomly divided into the study group and the control group according to random number table method,with 30 patients in each group.All patients in the two groups were required to take low-salt and low-fat diabetic diet and exercise for intervention,and were also given the conventional western medical treatment with hypoglycemic,lipid-lowering,antihypertensive,anti-platelet aggregation agents.Additionally,the study group was treated with Bushen Tongmai Prescription.The course of treatment for the two groups covered eight weeks.Before and after treatments,the two groups were observed in the changes of C-reactive protein(CRP),interleukin 1β(IL-1β),interleukin 6(IL-6),vascular cell adhesion molecule 1(VCAM1),miR-126,carotid intima-media thickness(CIMT),carotid plaque Crouse scores,and blood lipid indicators of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).After treatment,the therapeutic efficacy on carotid artery and drug safety in the two groups were evaluated.Results(1)After treatment,the serum miR-126 level in the study group was significantly increased compared with that before treatment(P<0.01),but the level in the control group only showed a rising trend and the difference was not statistically significant(P>0.05).The comparison between the two groups showed that the increase of serum miR-126 level in the study group was significantly superior to that in the control group(P<0.05).(2)After treatment,the serum VCAM1 level in the study group was decreased significantly compared with that before treatment(P<0.01),but the level in the control group only showed a rising trend and the difference was not statistically significant(P>0.05).The comparison between the two groups showed that the decrease of serum VCAM1 level in the study group was significantly superior to that in the control group(P<0.01).(3)After treatment,the serum CRP,IL-1 β,and IL-6 levels in the two groups were decreased compared with those before treatment(P<0.05 or P<0.01),and the decrease of serum IL-1β and IL-6 levels in the study group was significantly superior to that in the control group(P<0.05).(4)After treatment,the TC,TG and LDL-C levels in the study group were decreased(P<0.01)and the HDL-C level was increased compared with that before treatment(P<0.01),but in the control group,the changes in the TC,TG,LDL-C,and HDL-C levels were not significant(P>0.05).The comparison between the two groups showed that the decrease of TC and LDL-C levels in the study group was significantly superior to that in the control group(P<0.05).(5)After eight weeks of treatment,the total effective rate of the study group was 90.00%(27/30),while that of the control group was 63.33%(19/30).The intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the study group was significantly superior to that of the control group(P<0.05).(6)During the treatment,no serious adverse reactions or toxic-side effects occurred in the two groups.Conclusion Bushen Tongmai Prescription combined with conventional western medicine treatment can up-regulate the level of miR-126,inhibit the expression of VCAM1,and decrease the levels of serum CRP,IL-1β,and IL-6,so as to inhibit inflammatory response and retard the progression of T2DM complicated with ASCVD.The combined therapy exerts certain clinical efficacy and higher safety in treating T2DM complicated with ASCVD.
8.Establishment and evaluation of a lipopolysaccharide-induced acute respiratory distress syndrome model in minipigs
Chuang-Ye WANG ; Ran WANG ; Jian ZHANG ; Ling-Xiao QIU ; Bin QING ; Heng YOU ; Jin-Cheng LIU ; Bin WANG ; Nan-Bo WANG ; Jia-Yu LI ; Xing LIU ; Shuang WANG ; Jin HU ; Jian WEN ; Quan LI ; Xiao-Ou HUANG ; Kun ZHAO ; Shuang-Lin LIU ; Gang LIU ; Mei-Ju WANG ; Qing XIANG ; Hong-Mei WU ; Xiao-Rong SUN ; Tao GU ; Dong ZHANG ; Qi LI ; Zhi XU
Medical Journal of Chinese People's Liberation Army 2025;50(9):1154-1161
Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.
9.Inhibitory effects of toosendanin on in vitro and in vivo growth of lung adenocarcinoma cells by regulating CDCA5 expression
Zhi-Cheng ZHANG ; Li-Xia SU ; Rui-Ling MENG ; Wen-Juan GUAN ; Hong-Qian LI
The Chinese Journal of Clinical Pharmacology 2024;40(7):994-998
Objective To investigate the inhibitory effect of toosendanin on the growth of lung adenocarcinoma cells in vitro and in vivo by regulating the expression of cell division cycle associated protein 5(CDCA5).Methods The expression of CDCA5 in different lung tissues was analyzed in TCGA database.The expression level of CDCA5 in BEAS-2B cells and A549 cells was detected by Western blot.The effect of different concentrations of toosendanin on the viability of A549 cells was determined by cell counting kit-8(CCK-8)assay.The A549 cells were randomly divided into 4 groups:control group(normal cells cultured normally),toosendanin group(normal cells cultured with 40 μmol·L-1 toosendanin),toosendanin+pcDNA group(cells transfected with pcDNA empty vector and cultured with 40 μmol·L-1 toosendanin),and toosendanin+CDCA5 group(cells transfected with CDCA5 overexpression vector and cultured with 40 μmol·L-1 toosendanin).After 48 h of cultivation,the proliferation and apoptosis of each group of cells were detected by CCK-8 and flow cytometry,and the expression of proliferation and apoptosis related proteins in each group of cells was detected by Western blot.The BALB/c nude mice were randomly divided into sh-NC and sh-CDCA5 stable transfected cell lines with nude mouse xenograft models.Daily intraperitoneal injection of 0.9%NaCl and 40μmol·L-1 toosendanin solution was given to observe and record the changes in tumor tissue volume and body mass.Results The results of CCK-8 showed that after 48 hours,the survival rates of A549 cells treated with 10,20,30,40,50,60 and 70 μmol·L-1 toosendanin were(80.74±8.71)%,(72.96±6.53)%,(61.01±4.86)%,(51.20±3.13)%,(42.10±5.94)%,(38.93±3.18)%and(33.48±2.94)%,respectively.Toosendanin significantly inhibited the proliferation of A549 cells.The proliferation rates of cells in the control group,toosendanin group,toosendanin+pcDNA group,and toosendanin+CDCA5 group were(100.00±4.19)%,(49.18±6.70)%,(55.75±5.74)%,and(77.66±7.48)%,respectively;the expression levels of CDCA5 protein were 1.08±0.11,0.44±0.04,0.43±0.05 and 0.99±0.10,respectively.The expression levels of CDCA5 protein in tumor tissues of nude mice in the sh-NC group,sh-CDCA5 group,toosendanin+sh-NC group,and toosendanin+sh-CDCA5 group were 1.04±0.14,0.42±0.04,0.56±0.08 and 0.32±0.04,respectively.Compared with the sh-NC group,the tumor blocks formed by nude mice in other groups were significantly smaller,and the tumor volume and weight were significantly lower(all P<0.05).Compared with the toosendanin+sh-NC group,the toosendanin+sh-CDCA5 group had more significant inhibitory effect on tumor formation,and the difference was statistically significant(P<0.05).Conclusion Toosendanin can inhibit the growth of lung adenocarcinoma cells in vitro and in vivo,which is mainly related to the inhibition of CDCA5 expression.
10.Research status of AQP5 regulation of programmed cell death in chronic obstructive pulmonary disease
Cheng-Cai YUN ; Li-Ying ZHANG ; Hong-Dou HOU ; Huan-Huan ZHANG ; Zhang-Bo SONG ; Wen-Xing YONG
The Chinese Journal of Clinical Pharmacology 2024;40(14):2134-2138
Aquaporin 5(AQP5),as the main water transport protein in the body,can regulate lung diseases by regulating airway mucus secretion,pulmonary inflammation,and lung function.Programmed cell death(PCD)plays a crucial role in chronic obstructive pulmonary disease(COPD).AQP5 may affect the development of COPD by regulating PCDs.This article reviews the molecular regulatory mechanism of AQP5 on apoptosis,autophagy,iron death and pyroptosis in PCDs in recent years,and further discusses its effect on COPD in order to provide theoretical support for clinical prevention and treatment of COPD.

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