1.Influencing factors for atrial fibrillation in elderly patients with heart failure and construction of a nomogram model
Yakun SU ; Tingting LIN ; Qiong WANG ; Fengde LI ; Junying SONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1010-1015
Objective To elucidate the independent risk factors for AF in elderly patients with HF,develop a nomogram prediction model,and assess its predictive value for AF in elderly HF pa-tients.Methods A retrospective study was conducted on 299 patients of first HF hospitalization in Hengshui People's Hospital from June 2019 to December 2023,and based on the presence or absence of AF,they were divided into an AF group(133 cases)and a non-AF group(166 cases).The patients admitted from June 2019 to December 2022 were assigned into a modeling cohort(206 cases),while those from January 2023 to December 2023 into a validation cohort(93 cases).The general data were collected.Multivariate logistic regression analysis was performed on the modeling cohort to identify the independent predictors of AF in elderly HF patients,and a nomo-gram prediction model was constructed.ROC curve,calibration curve and clinical decision curve analyses were applied to evaluate the discrimination,calibration and clinical practicability of the prediction model.Results Multivariate logistic regression analysis revealed that the etiology of HF(CHD vs HP,OR=0.610,95%CI:0.301-1.250,P=0.178;CMD vs HP,OR=0.213,95%CI:0.052-0.883,P=0.033),LAD(OR=1.081,95%CI:1.020-1.152,P=0.015),HF classifi-cation(HFmrEF vs HFrEF,OR=5.897,95%CI:2.448-14.201,P=0.000;HFpEF vs HFrEF,OR=7.211,95%CI:2.522-20.640,P=0.001),pre-albumin(PALB)(OR=0.438,95%CI:0.217-0.901,P=0.030),UAC(OR=2.186,95%CI:1.075-4.430,P=0.025),and direct biliru-bin(DBi)(OR=4.531,95%CI:2.052-9.990,P=0.000)were independent risk factors for AF in the elderly HF patients.ROC curve analysis showed the AUC value of the prediction model based on these factors in the modeling cohort was 0.831,and the AUC value in the validation cohort was 0.840.Decision curve analysis indicated that the model possessed clinical practicability within a probability threshold range of 10%-82%for the modeling cohort and 12%-100%for the vali-dation cohort.Conclusion Our nomogram prediction model based on multivariate logistic regres-sion analysis exhibits good predictive value for the occurrence of AF in elderly HF patients,and can facilitate clinical decision-making on diagnosis and treatment.
2.Bioinformatics analysis and expression of the major genetic type of TcdB
Yitai Fang ; Nianzhi Ning ; Yakun Sun ; Deyu Li ; Hui Wang ; Deyan Luo
Acta Universitatis Medicinalis Anhui 2025;60(12):2273-2280
Objective:
To analyze the bioinformatics of domestic Clostridium difficile toxin B(TcdB) and prepare it to provide data support for the development of effective vaccines.
Methods:
Using bioinformatics software such as Snippy, Blast, Muscle, and the dist.alignment() and hclust() functions in R, 1 355 strains of Clostridium difficile from NCBI GenBank in China were compared and analyzed, and TcdB were grouped. The maximum likelihood tree and phylogenetic tree were beautified and displayed using iTOL. An online bioinformatics analysis website was used to predict and analyze the spatial structure and antigenic epitopes of the two largest subgroups, TcdB1 and TcdB2. The antigen protein TcdB was expressed and purified by prokaryotic system.
Results:
According to the genotype of toxin B, the 1 355 prevalent strains of Clostridium difficile in China could be roughly divided into 12 subtypes, among which TcdB1 and TcdB2 were the main subtypes, accounting for more than 93.94% of all isolated strains, and about 17.20% of the strains were nontoxigenic or lack TcdB. The antigen epitope prediction of TcdB1 and TcdB2 showed that their antigen epitope distributions were basically the same, and many of them were distributed outside the C-terminal combined repetitive oligopeptides domains.
Conclusion
A specialized typing system for C. difficile TcdB in China has been established, and its main subtypes have been predicted for antigenic epitopes. The screened TcdB has been expressed for recombinant preparation.
3.Research progress on mechanisms and animal models of comorbid depression and tumors
Yakun REN ; Xinpei WANG ; Xingjiu YANG ; Mengyuan LI ; Ran GAO
Acta Laboratorium Animalis Scientia Sinica 2025;33(9):1393-1402
The comorbidity of depression and cancer represents a significant global public health challenge,severely impacting patients' quality of life and clinical outcomes.This systematic review considers the epidemiological characteristics,clinical implications,and major challenges in current research regarding comorbid depression and cancer,focusing on the role of depression in promoting tumor progression and suppressing immune function via the neuroendocrine-immune regulatory network.We discuss the dynamic changes and interaction mechanisms of depression-related neurotransmitters(such as serotonin and norepinephrine)and stress hormones(such as cortisol)within the tumor microenvironment.We also reveal the molecular mechanisms by which depression regulates malignant biological behaviors such as tumor immune evasion,metastasis,and angiogenesis via activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.This review also evaluates the application value and limitations of existing animal models for studying the mechanisms underlying the comorbidity of depression and cancer,emphasizing the importance and urgency of developing more precise comorbidity models to uncover the mechanisms and explore management strategies.This review aims to raise awareness of risk prediction,clinical interventions,and basic research on the comorbidity of depression and cancer,to provide a theoretical foundation and new research directions for developing depression-cancer comorbidity models.
4.Research progress on mechanisms and animal models of comorbid depression and tumors
Yakun REN ; Xinpei WANG ; Xingjiu YANG ; Mengyuan LI ; Ran GAO
Acta Laboratorium Animalis Scientia Sinica 2025;33(9):1393-1402
The comorbidity of depression and cancer represents a significant global public health challenge,severely impacting patients' quality of life and clinical outcomes.This systematic review considers the epidemiological characteristics,clinical implications,and major challenges in current research regarding comorbid depression and cancer,focusing on the role of depression in promoting tumor progression and suppressing immune function via the neuroendocrine-immune regulatory network.We discuss the dynamic changes and interaction mechanisms of depression-related neurotransmitters(such as serotonin and norepinephrine)and stress hormones(such as cortisol)within the tumor microenvironment.We also reveal the molecular mechanisms by which depression regulates malignant biological behaviors such as tumor immune evasion,metastasis,and angiogenesis via activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.This review also evaluates the application value and limitations of existing animal models for studying the mechanisms underlying the comorbidity of depression and cancer,emphasizing the importance and urgency of developing more precise comorbidity models to uncover the mechanisms and explore management strategies.This review aims to raise awareness of risk prediction,clinical interventions,and basic research on the comorbidity of depression and cancer,to provide a theoretical foundation and new research directions for developing depression-cancer comorbidity models.
5.Advances in the application of gene copy number alteration detection technology in lymphoma
Yu PENG ; Shuang CHEN ; Tingting JIANG ; Can LIN ; Longrong RAN ; Xuelian WU ; Lian LI ; Liangmei LI ; Xinyi TANG ; Yakun ZHANG ; Huiyu XIANG ; Junxi LIU ; Dan JI ; Zailin YANG
International Journal of Laboratory Medicine 2025;46(15):1860-1866
Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.
6.Milk fat globule-epidermal growth factor 8 alleviates intestinal inflammation and ferroptosis in mice with acute pancreatitis through integrin αVβ3 receptor
Bingli LIU ; Yakun SHI ; Hua LI ; Yiming LI
Chinese Journal of Digestion 2025;45(8):548-554
Objective:To investigate the protective effects and mechanism of exogenous milk fat globule-epidermal growth factor 8(MFG-E8) on intestinal injury and ferroptosis in mice with acute pancreatitis (AP) and its mechanism.Methods:A total of 24 male C57 BL/6 mice were randomly divided into the normal control group, AP group, AP+ MFG-E8 group (MFG-E8 group), and AP+ MFG-E8+ cilengitide group (cilengitide group), with 6 mice in each group according to the random number table. The mice of normal control group were intraperitoneally injected with 0.9% sodium chloride solution. In the AP group, MFG-E8 group, and cilengitide group, the mice were intraperitoneally injected with 8% L-arginine twice at 1-hour intervals to induce the AP model. In the MFG-E8 group, mice were intraperitoneally injected with 20 g/kg of MFG-E8 at 2 hours after L-arginine injection. In the cilengitide group, mice were intraperitoneally injected with 20 mg/kg of cilengitide at 1 hour after the L-arginine injection, and 20 g/kg of MFG-E8 1 hour later. The mice were sacrificed and blood samples and intestinal tissues were collected at 72 hours after the first L-arginine injection. Hematoxylin-eosin staining was used to evaluate intestinal tissue injury. Myeloperoxidase (MPO) immunofluorescence staining was performed to detect neutrophils in intestinal tissues.Adenosinetriphosphate (ATP) levels were examined to detect changes in mitochondrial function. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were tested to check the level of intestinal oxidative stress. Dihydroethidium (DHE) fluorescent probe was used to label the oxygen free radicals in intestinal tissues. The expression of glutathione peroxidase 4 (GSH-Px4), solute carrier family 7 member 11 (also named xCT), and ferroptosos suppressor protein-1 (FSP-1) in intestinal tissues were detected by western blotting. Indepent-samples t-test, one-way ANOVA, and Student-Newman-Keuls test were performed for statistical analysis. Results:Intestinal tissue injury and inflammatory cell infiltration in mice were induced by intraperitoneal injection of L-arginine. Compared with those of AP model group, the intestinal pathology score, MPO fluorescence quantification and DHE fluorescence density of MFG-E8 group were significantly decreased (3.93±0.57 vs. 1.73±0.74, (26.33±4.49)/field vs. (11.00±3.27)/field, (39.67±5.79)/field vs. (12.33±3.68)/field), while the contents of ATP, MDA and SOD were increased ((77.09±8.52) μmol/g vs. (119.87±6.83) μmol/g, (0.10±0.01) μmol/g vs. (0.17±0.02) μmol/g, (105.67±6.93) U/mg vs. (144.49±18.55) U/mg), and the differences were statistically significant ( t=3.33, 3.93, 5.63, 8.77, 6.54, 4.38; all P<0.05). The results of Western blotting showed that GSH-Px4, xCT, and FSP-1 in the intestinal tissue of AP mice in the MFG-E8 group were all elevated compared with those of AP group, the relative expression levels were 1.22±0.19 vs. 0.55±0.09, 1.48±0.12 vs. 0.34±0.08, and 0.48±0.08 vs. 0.04±0.03, and the differences were statistically significant ( t=5.60, 14.39, 9.53; all P<0.05). Intraperitoneal injection of integrin αVβ3 receptor inhibitor cilengitide effectively antagonized the protective effects of MFG-E8 on intestinal injury in AP mice. Compared with MFG-E8 group, the histopathological score, MPO quantification and DHE fluorescence density of cilengitide group (3.53±0.50, (27.67±6.02)/field, and (31.33±3.86)/field, respectively) all increased, the expression of ATP, MDA and SOD were inhibited ((77.41±8.51) μmol/g, (0.19±0.04) mol/g, (100.46±8.15) U/mg); and GSH-Px4, xCT and FSP-1 all decreased, with the relative expression levels of 0.59±0.11, 0.16±0.06, and 0.10±0.03, respectively, and the differences were statistically significant ( t=3.02, 3.44, 5.04, 8.70, 4.01, 4.86, 5.05, 17.47, 8.34; all P<0.05). Conclusion:MFG-E8 alleviates intestinal oxidative stress and ferroptosis by integrin αVβ3 receptor, thereby reducing intestinal injury and inflammation in AP mice.
7.Influencing factors for atrial fibrillation in elderly patients with heart failure and construction of a nomogram model
Yakun SU ; Tingting LIN ; Qiong WANG ; Fengde LI ; Junying SONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1010-1015
Objective To elucidate the independent risk factors for AF in elderly patients with HF,develop a nomogram prediction model,and assess its predictive value for AF in elderly HF pa-tients.Methods A retrospective study was conducted on 299 patients of first HF hospitalization in Hengshui People's Hospital from June 2019 to December 2023,and based on the presence or absence of AF,they were divided into an AF group(133 cases)and a non-AF group(166 cases).The patients admitted from June 2019 to December 2022 were assigned into a modeling cohort(206 cases),while those from January 2023 to December 2023 into a validation cohort(93 cases).The general data were collected.Multivariate logistic regression analysis was performed on the modeling cohort to identify the independent predictors of AF in elderly HF patients,and a nomo-gram prediction model was constructed.ROC curve,calibration curve and clinical decision curve analyses were applied to evaluate the discrimination,calibration and clinical practicability of the prediction model.Results Multivariate logistic regression analysis revealed that the etiology of HF(CHD vs HP,OR=0.610,95%CI:0.301-1.250,P=0.178;CMD vs HP,OR=0.213,95%CI:0.052-0.883,P=0.033),LAD(OR=1.081,95%CI:1.020-1.152,P=0.015),HF classifi-cation(HFmrEF vs HFrEF,OR=5.897,95%CI:2.448-14.201,P=0.000;HFpEF vs HFrEF,OR=7.211,95%CI:2.522-20.640,P=0.001),pre-albumin(PALB)(OR=0.438,95%CI:0.217-0.901,P=0.030),UAC(OR=2.186,95%CI:1.075-4.430,P=0.025),and direct biliru-bin(DBi)(OR=4.531,95%CI:2.052-9.990,P=0.000)were independent risk factors for AF in the elderly HF patients.ROC curve analysis showed the AUC value of the prediction model based on these factors in the modeling cohort was 0.831,and the AUC value in the validation cohort was 0.840.Decision curve analysis indicated that the model possessed clinical practicability within a probability threshold range of 10%-82%for the modeling cohort and 12%-100%for the vali-dation cohort.Conclusion Our nomogram prediction model based on multivariate logistic regres-sion analysis exhibits good predictive value for the occurrence of AF in elderly HF patients,and can facilitate clinical decision-making on diagnosis and treatment.
8.Milk fat globule-epidermal growth factor 8 alleviates intestinal inflammation and ferroptosis in mice with acute pancreatitis through integrin αVβ3 receptor
Bingli LIU ; Yakun SHI ; Hua LI ; Yiming LI
Chinese Journal of Digestion 2025;45(8):548-554
Objective:To investigate the protective effects and mechanism of exogenous milk fat globule-epidermal growth factor 8(MFG-E8) on intestinal injury and ferroptosis in mice with acute pancreatitis (AP) and its mechanism.Methods:A total of 24 male C57 BL/6 mice were randomly divided into the normal control group, AP group, AP+ MFG-E8 group (MFG-E8 group), and AP+ MFG-E8+ cilengitide group (cilengitide group), with 6 mice in each group according to the random number table. The mice of normal control group were intraperitoneally injected with 0.9% sodium chloride solution. In the AP group, MFG-E8 group, and cilengitide group, the mice were intraperitoneally injected with 8% L-arginine twice at 1-hour intervals to induce the AP model. In the MFG-E8 group, mice were intraperitoneally injected with 20 g/kg of MFG-E8 at 2 hours after L-arginine injection. In the cilengitide group, mice were intraperitoneally injected with 20 mg/kg of cilengitide at 1 hour after the L-arginine injection, and 20 g/kg of MFG-E8 1 hour later. The mice were sacrificed and blood samples and intestinal tissues were collected at 72 hours after the first L-arginine injection. Hematoxylin-eosin staining was used to evaluate intestinal tissue injury. Myeloperoxidase (MPO) immunofluorescence staining was performed to detect neutrophils in intestinal tissues.Adenosinetriphosphate (ATP) levels were examined to detect changes in mitochondrial function. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were tested to check the level of intestinal oxidative stress. Dihydroethidium (DHE) fluorescent probe was used to label the oxygen free radicals in intestinal tissues. The expression of glutathione peroxidase 4 (GSH-Px4), solute carrier family 7 member 11 (also named xCT), and ferroptosos suppressor protein-1 (FSP-1) in intestinal tissues were detected by western blotting. Indepent-samples t-test, one-way ANOVA, and Student-Newman-Keuls test were performed for statistical analysis. Results:Intestinal tissue injury and inflammatory cell infiltration in mice were induced by intraperitoneal injection of L-arginine. Compared with those of AP model group, the intestinal pathology score, MPO fluorescence quantification and DHE fluorescence density of MFG-E8 group were significantly decreased (3.93±0.57 vs. 1.73±0.74, (26.33±4.49)/field vs. (11.00±3.27)/field, (39.67±5.79)/field vs. (12.33±3.68)/field), while the contents of ATP, MDA and SOD were increased ((77.09±8.52) μmol/g vs. (119.87±6.83) μmol/g, (0.10±0.01) μmol/g vs. (0.17±0.02) μmol/g, (105.67±6.93) U/mg vs. (144.49±18.55) U/mg), and the differences were statistically significant ( t=3.33, 3.93, 5.63, 8.77, 6.54, 4.38; all P<0.05). The results of Western blotting showed that GSH-Px4, xCT, and FSP-1 in the intestinal tissue of AP mice in the MFG-E8 group were all elevated compared with those of AP group, the relative expression levels were 1.22±0.19 vs. 0.55±0.09, 1.48±0.12 vs. 0.34±0.08, and 0.48±0.08 vs. 0.04±0.03, and the differences were statistically significant ( t=5.60, 14.39, 9.53; all P<0.05). Intraperitoneal injection of integrin αVβ3 receptor inhibitor cilengitide effectively antagonized the protective effects of MFG-E8 on intestinal injury in AP mice. Compared with MFG-E8 group, the histopathological score, MPO quantification and DHE fluorescence density of cilengitide group (3.53±0.50, (27.67±6.02)/field, and (31.33±3.86)/field, respectively) all increased, the expression of ATP, MDA and SOD were inhibited ((77.41±8.51) μmol/g, (0.19±0.04) mol/g, (100.46±8.15) U/mg); and GSH-Px4, xCT and FSP-1 all decreased, with the relative expression levels of 0.59±0.11, 0.16±0.06, and 0.10±0.03, respectively, and the differences were statistically significant ( t=3.02, 3.44, 5.04, 8.70, 4.01, 4.86, 5.05, 17.47, 8.34; all P<0.05). Conclusion:MFG-E8 alleviates intestinal oxidative stress and ferroptosis by integrin αVβ3 receptor, thereby reducing intestinal injury and inflammation in AP mice.
9.Expression of interleukin-36 and its regulatory effect on monocyte function in patients with diabetic kidney disease
Jiangyan LI ; Yakun KONG ; Jianlin ZHAO ; Lichao ZHAO ; Chengyun XIONG ; Yanhong ZHOU
Chinese Journal of Endocrinology and Metabolism 2024;40(1):30-36
Objective:To analyze the level of interleukin-36(IL-36) family cytokines in peripheral blood, and explore the regulatory role of recombinant human IL-36α in monocyte function in patients with diabetic kidney disease(DKD).Methods:A total of 41 type 2 diabetes mellitus(T2DM) patients, 36 DKD patients, and 20 controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMCs) were isolated. Enzyme-linked immunosorbent assay(ELISA) was used to measure plasma levels of IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist(IL-36Ra). PBMCs were sorted, and real-time quantitative PCR was performed to detect the mRNA expression of IL-36 receptor subunits in monocytes. Monocytes were stimulated with recombinant IL-36α, and levels of cytotoxic molecules and cytokines in the culture supernatant were measured. Flow cytometry was used to assess the expressions of programmed death receptor-1(PD-1) and cytotoxic T-lymphocyte-associated protein 4(CTLA-4). Co-culture of monocytes with Vero cells was performed to evaluate monocyte cytotoxicity.Results:Plasma levels of IL-36α and IL-36β in the T2DM and DKD groups were significantly higher than those in the control group. The DKD group also showed higher plasma levels of IL-36α compared to the T2DM group( P<0.05). There were no significant differences in IL-36γ and IL-36Ra levels among the three groups( P>0.05). The mRNA expression of IL-36 receptor subunits in monocytes was comparable among the three groups( P>0.05). The DKD group had higher level of tumor necrosis factor-alpha(TNF-α) compared to the control and T2DM groups( P<0.05). The levels of PD-1 and CTLA-4 were lower in the DKD group than those in the control and T2DM groups( P<0.05). The proportion of monocyte-induced Vero cell death was significantly higher in the DKD group compared to the control and T2DM groups( P<0.05). After stimulation with recombinant human IL-36α, monocytes from DKD patients showed a significant increase in the secretion of granzyme B and TNF-α( P<0.05), as well as an increased proportion of monocyte-induced Vero cell death( P=0.024). Conclusion:In DKD patients, elevated IL-36α and granzyme B levels in monocytes enhance monocyte function.
10.Silibinin inhibits lipogenic differentiation of 3T3-F442A adipocytes in murine through inhibition of MEK /ERK pathway and matrix metalloproteinase activity
Aiping Liu ; Tong Li ; Yaqing Cheng ; Renwen Zhang ; Yakun Ge ; Yuanxin Zhang
Acta Universitatis Medicinalis Anhui 2024;59(1):111-117
Objective :
To study the effect and mechanism of action of Silibinin on the differentiation of 3T3-F442A preadipocytes in murine.
Methods :
The effects of 0-400 μmol / L Silibinin on the proliferation of 3T3-F442A adi- pocytes at 24,48 and 72 h were detected by 3-(4,5-dimethylthiazol-2) -2,5-diphenyltetrazolium bromide ( MTT) assay,and the effects of Silibinin on the adipogenesis of 3T3-F442A adipocytes were visualized by Oil Red O stai- ning ; RT-qPCR , Western blot and ELISA assays were used to detect the effects of Silibinin on 3T3-F442A adipo- cyte differentiation-associated transcription factor CCAAT / enhancer binding protein ( C / EBP) α , C / EBP β , per- oxisome proliferator-activated receptor γ cular endothelial growth factor (VEGF) -α and VEGF receptor 2 (VEGFR-2) ,matrix metalloproteinase (MMP) -2 and MMP-9,mitogen-activated protein kinase (MEK) and phosphorylated MEK (p-MEK) ,and extracellular regu- lated protein kinase (ERK) and phosphorylated ERK (p-ERK) expression. (PPARγ) ,adipocyte protein 2 (aP2) ,adipose generation-associated vas
Results :
MTT assay showed that the cell proliferation rate of 3T3-F442A preadipocytes decreased after 100,200,and 400 μmol /L Silibinin treatment compared with the control group (P<0. 001) ; Oil Red O staining assay showed that the accumulation of red lipid droplets of the cells in the 160 μmol /L Silibinin assay group significantly decreased ; RT-qPCR assay showed that mRNA expression of C/EBPα , C/EBPβ , PPARγ , aP2,VEGF-α , VEGFR-2,MMP-2,and MMP-9 was down-reg- ulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin compared with the control group (P<0. 001) ; Western blot assay showed that protein expression of C /EBPα , C /EBPβ , PPARγ and aP2 was down-regulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin (P<0. 001) ,and the phosphorylation level of p-MEK/ MEK and p-ERK/ ERK proteins was down-regulated compared with the control group (P <0. 001) ; ELISA assay showed that the protein concentrations of MMP-2 and MMP-9 in the cell supernatant were down-regulated (P < 0. 001) in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin.
Conclusion
Silibinin inhibited 3T3-F442A adipocyte differentiation and adipogenesis through inhibition of the MEK/ ERK pathway and matrix metalloproteinase activity.


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