1.An Amphibians-Derived Protein Provides Novel Biotherapeutics for Various Wounds Treatment
Hao-Ran CHEN ; Nan ZHOU ; Yu-Da LIU ; Li-Hua PENG
Biomolecules & Therapeutics 2025;33(2):399-407
Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.
2.An Amphibians-Derived Protein Provides Novel Biotherapeutics for Various Wounds Treatment
Hao-Ran CHEN ; Nan ZHOU ; Yu-Da LIU ; Li-Hua PENG
Biomolecules & Therapeutics 2025;33(2):399-407
Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.
3.An Amphibians-Derived Protein Provides Novel Biotherapeutics for Various Wounds Treatment
Hao-Ran CHEN ; Nan ZHOU ; Yu-Da LIU ; Li-Hua PENG
Biomolecules & Therapeutics 2025;33(2):399-407
Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.
4.Estimation of the excess cases of hand-foot-mouth disease in Beijing with adjusted Serfling regression model
Shuaibing DONG ; Ruitong WANG ; Da HUO ; Baiwei LIU ; Hao ZHAO ; Zhiyong GAO ; Xiaoli WANG ; Peng YANG ; Quanyi WANG ; Daitao ZHANG
Shanghai Journal of Preventive Medicine 2025;37(3):206-209
ObjectiveTo establish an adjusted Serfling regression model to estimate the excess cases and the excess epidemic period of hand-foot-mouth disease (HFMD) in Beijing from 2011 to 2019, so as to provide data support and decision-making basis for HFMD prevention and control. MethodsThe weekly number of HFMD cases in Beijing from 2011 to 2019 was utilized for adjusted the Serfling regression model. Then the adjusted model was used to fit the baseline and epidemic threshold of HFMD in Beijing from 2011 to 2019, calculating the excess cases and determining the excess epidemic period. ResultsA total of 279 306 cases of HFMD were reported in Beijing from 2011 to 2019, with the climax of the disease occurring in summer and autumn. After adjusting the fitting R2 of the Serfling regression model to 0.773, a total of 10 excess epidemic periods totaling 92 weeks were estimated, mainly occurring in summer. The highest number of excess cases during an excess epidemic period was found in 2014 (1 272 cases, 95%CI: 990‒1 554), accounting for 65.04% of the actual cases (95%CI: 50.62%‒79.46%). ConclusionThe adjusted Serfling regression model fits well and can be utilized for early warning of HFMD and estimating the disease burden caused by HFMD.
5.Association between the Non-Fasting Triglyceride-Glucose Index and Hyperglycemia in pregnancy during the Third Trimester in High Altitudes
Qingqing WANG ; Hongying HOU ; Ma NI ; Yating LIANG ; Xiaoyu CHEN ; WA Zhuoga DA ; Qiang LIU ; Zhenyan HAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(5):861-871
ObjectiveTo investigate the relationship between the non-fasting triglyceride and glucose (TyG) index and hyperglycemia in pregnancy during the third trimester in high altitudes. MethodsThis study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region, from January 2023 to April 2025. The non-fasting TyG index was calculated from non-fasting triglyceride (TG) and random plasma glucose (PG). Based on the tertiles of the non-fasting TyG index values, the individuals were split into three groups (corresponding to non-fasting TyG index of 8.89 and 9.21, respectively). The baseline clinical characteristics, lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups. Statistical analyses were performed using ANOVA, Kruskal-Wallis H test, Chi-square test, or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting. ResultsA total of 774 Tibetan singleton pregnant women were included, with a average age of 27.3 ± 6.1 years, a pre-delivery body mass index (Pre-BMI) of (25.2±2.3)kg/m2 , a proportion of 26.7% (207/774) primigravid women, the mean non-fasting TyG index was 9.1 ± 0.4。Thirty pregnant women were diagnosed with hyperglycemia in pregnancy, with a detection rate of 3.9% (30/774). Statistically significant differences in serum total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were identified when comparing different non-fasting TyG groups (all P values <0.05). Subsequent trend test analysis indicated that the levels of TC, TG, LDL-C, and PG gradually increased with elevated the non-fasting TyG index ( Ftrend TC=95.61, P<0.001; Ftrend TG=1 051.91, P<0.001; Ftrend LDL-C = 97.20, P < 0.001; Ftrend TG=195.20; P<0.001). After adjustment for maternal age, pre-delivery BMI, altitude, TC, LDL-C, and HDL-C, multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy (Model 1: OR=2.72, 95% CI: 1.13-6.53, P=0.026; Model 2: OR=2.56, 95% CI: 1.01-6.50, P=0.048; Model 3: OR=2.72, 95% CI: 1.06-6.97, P=0.037; Model 4: OR=4.02, 95% CI: 1.42-11.40, P=0.009) and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index, however, this association did not statistical significance (P trend >0.05). Curve fitting by restricted cubic splines (RCS) were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy, and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy (P for non-linear = 0.515). ConclusionNon-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.
6.Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance
Xianlong WANG ; Chuan ZHAO ; Jincheng LIN ; Hongxing LIU ; Qiuhong ZENG ; Huadong CHEN ; Ye WANG ; Dapeng XU ; Wen CHEN ; Moping XU ; En ZHANG ; Da LIN ; Zhixiong LIN
Chinese Medical Journal 2024;137(7):859-870
Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.
7.Ginkgo biloba extract activates Nrf2/ARE pathway to improve vascular endothelial dysfunction induced by chronic intermittent hypoxia in rats
Sheng-Yong SI ; Hong-Man LI ; Si-Si MIAO ; Xiao HAN ; Zhi-Jing LI ; Chao-Jun WEI ; Da-Nan LIU
Chinese Pharmacological Bulletin 2024;40(10):1837-1844
Aim To investigate the effects of Ginkgo biloba extract(GBE)on vascular endothelial dysfunc-tion induced by chronic intermittent hypoxia(CIH)in rats and its related mechanisms.Methods The CIH rat model was established,and 50 and 100 mg·kg-1 GBE was administered by intragastric administration.The systolic blood pressure(SBP)of the tail artery was detected in each group.HE staining was used to detect the morphology of aorta tissue.DAF-FM DA staining and nitric reductase assay were used to detect NO levels.ELISA was used to detect serum ET-1,TNF-α and IL-6 levels.DHE staining was used to de-tect reactive oxygen species(ROS)levels of aortic tis-sue.Kits were used to detect the serum levels of MDA,SOD and GSH-Px.Western blot was used to detect the levels of VCAM-1,ICAM-1,nucleus Nrf2,HO-1 and NQO1 of aortic tissue.Results GBE sig-nificantly decreased the levels of SBP,ET-1,ROS,MDA,VCAM-1,ICAM-1,TNF-α and IL-6,and sig-nificantly increased the levels of NO,SOD,GSH-Px,nuclear Nrf2,HO-1 and NQO1 in CIH rats.GBE sig-nificantly improved the histomorphology of aorta in CIH rats.Conclusions GBE can improve vascular endo-thelial dysfunction and reduce blood pressure in CIH model rats.The mechanism may be related to the acti-vation of Nrf2/ARE pathway and the inhibition of oxi-dative stress and inflammation by GBE.
8.Effect of repairing cartilage defects with PRP and ADSCs loaded calcium alginate gel
Journal of Regional Anatomy and Operative Surgery 2024;33(5):393-398
Objective To investigate the effect of platelet-rich plasma(PRP)combined with adipose-derived stem cells(ADSCs)loaded calcium alginate gel on repairing cartilage defects.Methods ADSCs were isolated and cultured from subcutaneous fat of New Zealand white rabbits.The rabbit articular cartilage defect model was created,and then ADSCs were implanted onto PRP loaded calcium alginate gel to construct tissue engineered cartilage and transplant to the defect.The experiment was divided into three groups:the control group,the PRP group and the PRP ADSCs calcium alginate gel group,with 10 rabbits in each group.The morphology and growth of cells were observed after operation.Toluidine blue staining and type Ⅱ collagen immunohistochemical staining were used to detect the chondrogenic characteristics of ADSCs.CCK-8 method was used to detect the proliferation activity of ADSCs.RT-PCR was used to detect the expression of type Ⅱcollagen mRNA and proteoglycan mRNA.Results Under the inverted phase contrast microscope,ADSCs showed typical morphology of mesenchymal stem cells,which was spindle or oval,with abundant cytoplasm and regular nuclear shape.With the extension of culture time,ADSCs gradually showed a good growth state,the number of cells increased,the connection between cells was tight,and the morphology was regular.In the control group,there was no obvious repair in the cartilage defect area,with light blue staining and a large number of ADSCs.The cartilage defect area in the PRP group was partially repaired and stained blue,and the number of ADSCs was more than that in the control group.The repair effect of cartilage defect area in the PRP ADSCs calcium alginate gel group was the best,the staining was dark blue,and the number of ADSCs was more than that in the PRP group.After 14 days of induction,the ADSCs were positive for toluidine blue metachromostaining,and purple red metachromostaining appeared in the cytoplasm and the surrounding cells.Type Ⅱ collagen immunohis-tochemical staining showed that the average gray value of ADSCs cells in the PRP ADSCs calcium alginate gel group was significantly higher than that in other groups(P<0.05);and the positive cells showed brownish yellow granules in the cytoplasm and yellow staining around the cells.CCK-8 test showed that the ADSCs in the PRP ADSCs calcium alginate gel group entered exponential growth on the second day,and that in the control group began to enter exponential growth on the third day.During the observation period,the OD value of ADSCs in the PRP ADSCs calcium alginate gel group was significantly higher than that in other groups(P<0.05).The expression of type II collagen mRNA in the PRP ADSCs calcium alginate gel group was significantly higher than that in other groups(P<0.05).The proteoglycan mRNA expression of ADSCs in the three groups increased with time.On the 14th and 21st day,the proteoglycan mRNA expression of ADSCs in the PRP ADSCs calcium alginate gel group was significantly higher than that in other groups(P<0.05).Conclusion The tissue engineered cartilage constructed by the complex formed by PRP,ADSCs and calcium alginate gel can improve the proliferation activity of ADSCs and the mRNA expression levels of collagen type II and proteoglycan,and the defective articular cartilage can be repaired significantly.
9.Predictive value of serum sFlt-1 and LTB4 for cerebral vasospasm after interventional embolization of intracranial aneurysms
Bing CAO ; Qi DING ; Yong-Da LIU ; Zhi-Wei DONG ; Yuan HOU ; Chun-Jiang LIU ; Xin-Wen XU
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1062-1066
Objective To explore the predictive value of soluble fms-like tyrosine kinase-1(sFlt-1)and leukotriene B4(LTB4)in patients with intracranial aneurysms for cerebral vasospasm(CVS)after interventional embolization.Methods A total of 98 patients with intracranial aneurysms admitted to our hospital from January 2019 to September 2023 were regarded as the observation group,and were divided into the CVS group(32 cases)and the non CVS group(66 cases)according to whether CVS occurred or not within 3 to 5 days after surgery;102 healthy examinees in our hospital were selected as the control group.Enzyme-linked immunosorbent assay was used to detect serum levels of sFlt-1 and LTB4;the influencing factors for CVS after interventional embolization of intracranial aneurysms were analyzed by Logistic regression analysis;the predictive value of serum sFlt-1 and LTB4 levels for the occurrence of CVS after interventional embolization of intracranial aneurysms was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of sFlt-1 and LTB4 of patients in the observation group were obviously higher than those in the control group,and the differences were statistically significant(P<0.05).The serum levels of sFlt-1 and LTB4,and the proportions of patients with postoperative blood pressure fluctuation range≥30 mmHg and Hunt-Hess grade Ⅲ in the CVS group were obviously higher than those in the non CVS group,and the differences were statistically significant(P<0.05).SFlt-1(OR:2.985;95%CI:1.684 to 5.291)and LTB4(OR:2.868;95%CI:1.581 to 5.204)were the independent risk factors for CVS after interventional embolization of intracranial aneurysms(P<0.05).The area under the curve(AUC)of sFlt-1 and LTB4 alone and in combination for predicting the occurrence of CVS after interventional embolization of intracranial aneurysms were 0.839,0.825,and 0.915,respectively,with sensitivity of 84.44%,87.59%,and 81.36%,and specificity of 74.26%,75.87%,and 90.98%,respectively.The AUC of the combination of the two was higher than those of sFlt-1 and LTB4 alone,and the differences were statistically significant(Z=2.150,2.546,P<0.05).Conclusion The serum levels of sFlt-1 and LTB4 in patients with CVS after interventional embolization of intracranial aneurysms are increased,and the combination of the two can serve as the important indicators for predicting CVS.
10.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

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