1.Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy.
Ting WEN ; Yanping FU ; Xiangting YI ; Ying SUN ; Wanchen ZHAO ; Chaonan SHI ; Ziyao CHANG ; Beibei YANG ; Shuling LI ; Chao LU ; Tingting PENG ; Chuanbin WU ; Xin PAN ; Guilan QUAN
Acta Pharmaceutica Sinica B 2025;15(7):3738-3755
Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO2 bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.
2.Effects of parthenolide on systemic inflammation and intestinal injury in rats with acute pancreatitis
Yanan ZHAO ; Rui ZHANG ; Shuling WANG ; Chunchun YANG ; Yang WANG ; Mingyue YANG
China Pharmacy 2025;36(6):704-709
OBJECTIVE To investigate the effects of parthenolide (PLT) on systemic inflammation and intestinal injury in rats with acute pancreatitis (AP) by regulating the Kelch-like epichlorohydrin-associated protein 1 (Keap1)/nuclear factor-erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. METHODS AP rat model was established by injecting 3.5% sodium taurine cholate solution (1 mL/kg) into the biliary pancreatic duct, and modeled rats were divided into AP group, PLT (300 µg/kg) group, dexamethasone (2 mg/kg) group, inhibitor (11 mg/kg Nrf2 inhibitor ML385) group, and PLT+inhibitor group (300 µg/kg PLT+11 mg/kg ML385), with 10 rats in each group. Another 10 rats were taken as a sham operation group. Each group was given relevant medicine or normal saline via tail vein/intraperitoneal injection once. After 24 h, serum lipase and amylase levels, the levels of oxidative stress index [superoxide dismutase (SOD) and malondialdehyde (MDA)] and inflammatory factors [interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α)] were detected. The histopathological changes in colon mucosa and pancreas were observed, and Chiu and Schmidt scores were performed. The cell apoptosis in colon mucosa and the protein expressions of Keap1, Nrf2 and HO-1 were detected. RESULTS Compared with the sham operation group, there was obvious inflammatory cell infiltration in colon mucosa and pancreatic tissue, cell shedding or tissue necrosis and severe bleeding; serum levels of lipase, amylase, MDA, IL-1β, IL-6 and TNF-α, Chiu and Schmidt scores, apoptotic rate and protein expression of Keap1 in colonic mucosa were significantly increased or up-regulated, while SOD level and protein expressions of Nrf2 20230993) and HO-1 were decreased or down-regulated significantly (P<0.05). Compared with the AP group, the above indexes in the PLT group and dexamethasone group were significantly improved, while those in the inhibitor group further deteriorated (P<0.05). Inhibitor could significantly reverse the improvement effect of PLT on the above indexes in AP rats (P< 0.05). CONCLUSIONS PLT inhibits inflammation and oxidative stress in AP rats, alleviates intestinal damage, and its mechanism may be related to inhibiting protein expression of Keap1 and activating Nrf2/HO-1 signaling pathway.
3.Epidemiological analysis of the adhesion glycoprotein gene characteristics of human respiratory syncytial virus in Xi'an from 2023 to 2024
Peng ZHANG ; Yangni DENG ; Shuling LI ; Yuewen HAN ; Yujie YANG ; Jianing WEI ; Ye ZHANG ; Yuanyuan DUAN ; Rui WU ; Hailong CHEN
Chinese Journal of Microbiology and Immunology 2025;45(10):809-816
Objective:To analyze the prevalence of human respiratory syncytial virus(RSV)and the evolutionary characteristics of the adhesion glycoprotein(G)gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR;full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected,with 104 cases(4.08%,104/2 548)testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year(12.24%,18/147),and significant difference in positivity rates were found among age groups(χ 2=37.868, P<0.001). Since October 2023,RSV has seen an epidemic peak during January to February 2024,and gradually declined thereafter,with no positive cases from May to September 2024. Among the 43 RSV-positive samples,12 strains were identified as subtype A(all genotype A.D.3),and 31 strains were subtype B(14 genotype B.D.4.1.1 and 17 genotype B.D.E.1). Conclusion:From October 2023 to October 2024,RSV had an epidemic peak in January and February in Xi'an,with subtype B being the predominant circulating type.
4.Effects of aerobic exercise on skeletal muscle mass and function in colon cancer-loaded mice
Hongli LI ; Luyu ZUO ; Shiliang HU ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):353-364
Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2~6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7~9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.
5.Effects of aerobic exercise preconditioning on cardiac protein metabolism and cardiac function in mice with subcutaneously transplanted tumors
Shiliang HU ; Luyu ZUO ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Chinese Journal of Sports Medicine 2025;44(7):560-569
Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.
6.Effects of aerobic exercise on skeletal muscle mass and function in colon cancer-loaded mice
Hongli LI ; Luyu ZUO ; Shiliang HU ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):353-364
Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2~6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7~9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.
7.Effects of aerobic exercise preconditioning on cardiac protein metabolism and cardiac function in mice with subcutaneously transplanted tumors
Shiliang HU ; Luyu ZUO ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Chinese Journal of Sports Medicine 2025;44(7):560-569
Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.
8.Epidemiological analysis of the adhesion glycoprotein gene characteristics of human respiratory syncytial virus in Xi'an from 2023 to 2024
Peng ZHANG ; Yangni DENG ; Shuling LI ; Yuewen HAN ; Yujie YANG ; Jianing WEI ; Ye ZHANG ; Yuanyuan DUAN ; Rui WU ; Hailong CHEN
Chinese Journal of Microbiology and Immunology 2025;45(10):809-816
Objective:To analyze the prevalence of human respiratory syncytial virus(RSV)and the evolutionary characteristics of the adhesion glycoprotein(G)gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR;full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected,with 104 cases(4.08%,104/2 548)testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year(12.24%,18/147),and significant difference in positivity rates were found among age groups(χ 2=37.868, P<0.001). Since October 2023,RSV has seen an epidemic peak during January to February 2024,and gradually declined thereafter,with no positive cases from May to September 2024. Among the 43 RSV-positive samples,12 strains were identified as subtype A(all genotype A.D.3),and 31 strains were subtype B(14 genotype B.D.4.1.1 and 17 genotype B.D.E.1). Conclusion:From October 2023 to October 2024,RSV had an epidemic peak in January and February in Xi'an,with subtype B being the predominant circulating type.
9.Research progress in the small G-protein Rac1.
Yiheng YANG ; Shuling ZHAO ; Changyong LIANG
Chinese Journal of Biotechnology 2024;40(11):3902-3911
The small G-protein Rac1 is the main regulatory factor of the actin cytoskeleton. Rac1 cycles between the inactive GDP-bound form and the active GTP-bound form. Rac1 not only promotes viral replication and infection, but also regulates the actin cytoskeleton rearrangement, adhesion, and invasion of glioma cells. In addition, Rac1 is implicated in human diseases such as tumors and epilepsy. This article reviews the latest research on the small G-protein Rac1 in virology, cell biology, and human pathology. It is found that the existence of Rac1 is closely related to the replication and infection of viruses, that is, inhibiting the existence of Rac1 can effectively reduce the replication and transportation of viruses, providing new ideas for the development of various therapeutic drugs targeting Rac1.
Humans
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rac1 GTP-Binding Protein/genetics*
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Virus Replication
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Glioma/pathology*
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Actin Cytoskeleton/metabolism*
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Animals
10.Epidemiological and clinical characteristics of brucellosis in Xinjiang Uygur Autonomous Region
Zhiwei LI ; Lingling WANG ; Shuling LI ; Qian WANG ; Shuting YANG ; Xuewei TONG ; Bingli WANG ; Peipei LU ; Changmin WANG
Chinese Journal of Endemiology 2024;43(7):575-579
Objective:To study the epidemiological and clinical characteristics of brucellosis in Xinjiang Uygur Autonomous Region.Methods:A retrospective analysis method was used to collect medical records of 581 patients with brucellosis who visited the Xinjiang Uygur Autonomous Regional People's Hospital from January 2009 to December 2019. Demographic and epidemiological characteristics, clinical symptoms and signs, and laboratory test results of the patients were analyzed.Results:Among 581 patients with brucellosis, the male to female ratio was 2.8 ∶ 1.0 (428 ∶ 153). The age was (44.41 ± 16.25) years old, ranging from 1 - 83 years old, and mainly concentrated in 35 - 60 years old, accounting for 70.91% (412/581). The ethnic distribution was dominated by Uyghur, accounting for 50.60% (294/581). The occupational distribution was mainly farmers, accounting for 43.20% (251/581). A total of 186 patients had a clear history of contact with cattle and sheep, accounting for 32.01% (186/581). The clinical stage was dominated by patients in the acute stage, accounting for 55.25% (321/581). There were 48 cases of complications, accounting for 8.26%(48/581). The main clinical symptom of brucellosis patients was pain and fever, accounting for 73.67% (428/581) and 66.61% (387/581), respectively. Laboratory tests were dominated by increased blood sedimentation and C-reactive protein, accounting for 29.09% (169/581) and 23.06% (134/581), respectively. The positive rate of Brucella culture was low, accounting for 4.48% (26/581). Conclusions:The majority of brucellosis patients in Xinjiang Uygur Autonomous Region are young and middle-aged males, with the main occupation being farmers. The clinical symptoms are mostly pain and fever. The positive rate of Brucella culture in patients is relatively low. It is recommended to combine epidemiological and clinical features for diagnosis to reduce missed diagnosis and misdiagnosis, and detect and treat it early.

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