1.The Functional Role of SUMOylation in The Tumor Microenvironment
Pan-Pan ZHAO ; Jun-Xu YU ; Ya-Ning CHE ; Hui-Yi LIANG ; Chao HUANG
Progress in Biochemistry and Biophysics 2024;51(6):1256-1268
Tumors continue to be a major challenge in human survival that we have yet to overcome. Despite the variety of treatment options available, we have not yet found an effective method. As more and more research is conducted, attention has been turned to a new field for tumor treatment—the tumor microenvironment (TME). This is a dynamic and complex environment consisting of various matrix cells surrounding cancer cells, including surrounding immune cells, blood vessels, extracellular matrix, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules, and some specific cell types. Firstly, endothelial cells play a key role in tumor development and the immune system’s protection of tumor cells. Secondly, immune cells, such as macrophages, Treg cells, Th17 cells, are widely involved in various immune responses and activities in the human body, such as inflammation responses promoting survival carefully orchestrated by the tumor. Even though many studies have extensively researched the TME and found many research schemes, so far, no key effective method has been found to treat tumors by affecting the TME. The TME is a key interaction area between the host immune system and the tumor. Cells within the TME influence each other and interact with cancer cells to affect cancer cell invasion, tumor growth, and metastasis. This is a new direction for cancer treatment. In the complex environment of the TME, post-translational modifications (PTMs) of proteins have been proven to play an important role in the TME. PTMs are dynamic, strictly regulated changes to proteins that control their function by regulating their structure, spatial location, and interaction. Among PTMs, a reversible post-translational modification called SUMOylation is a common regulatory mechanism in cellular processes. It is a post-translational modification that targets lysine residues with a small ubiquitin-like modifier (SUMO) in a reversible post-translational modification manner. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis, and apoptosis, playing a pivotal role in the TME, such as DNA damage repair, tumor metastasis, and also participates in immune cell differentiation, activation, and inhibition of immune cells. On the other hand, SUMO or sentrin-specific protease (SENP) inhibitors can interfere with the SUMOylation process, thereby affecting many biological processes, including immune response, carcinogenesis, cell cycle progression, and cell apoptosis, etc. In summary, this review aims to introduce the dynamic modification of protein SUMOylation on various immune cells and the application of various inhibitors, thereby exploring its role in the TME. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs. In conclusion, the TME is a complex and dynamic environment that plays a crucial role in the development and progression of tumors. Understanding the intricate interactions within the TME and the role of PTMs, particularly SUMOylation, could provide valuable insights into the mechanisms of tumor development and potentially lead to the development of novel therapeutic strategies. The study of SUMOylation and its effects on various immune cells in the TME is an exciting and promising area of research that could significantly advance our understanding of tumor biology and potentially lead to the development of more effective treatments for cancer. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs.
2.Effect of the setting of control point of Monaco radiotherapy planning system on dosimetry of dIMRT plan for esophageal cancer of middle and lower segment
Hao WANG ; Yunyi YANG ; Yi LI ; Qi DING ; Feng GUO ; Yantao GONG ; Genxiang CHEN ; Ya CHE ; Yinghong REN
China Medical Equipment 2024;21(9):1-6
Objective:To study the dosimetry effects of differently selected values of control point(CP)in Monaco radiotherapy planning system on dynamic intensity modulated radiation therapy(dIMRT)for esophageal cancer of middle and lower segment.Methods:Thirteen patients with esophageal cancer at middle and lower segment who received dIMRT in Shangluo Central Hospital from January to June 2023 were selected.In the Monaco radiotherapy planning system,nine groups of dIMRT plans were designed for each patient according to the 9 kinds of CP limit values(10,20,30,40,50,60,70,80 and 90).There were not changes in other optimized parameters except CP parameter.The differences of the dosimetry between target region and organs at risk(OAR)included lung,heart and spinal cord were analyzed.Results:With the increase of the CP limit value,the maximum dose of the target region which was radiation dose(D2%)of 2%volume of target region,the mean dose,which was radiation dose(D50%)of 50%volume of target region,and the homogeneity index(HI)appeared a trend of gradual stability after reduction,and the radiation dose(D98%)of 98%volume of target region which was the minimum dose of target region and the conformance index(CI)appeared a trend of gradual stability after increase.There was not significant in each dose indicator of OAR(P>0.05).The variation ranges of lung at 5,10,20,30 Gy dose(V5,V10,V20 and V30)were respectively 1.13%,0.75%,0.29%and 0.19%,and the maximum deviation of mean dose(Vmean)of lung was 18.7 cGy.The variation ranges of V10,V20,V30 and V40 in the heart were respectively 2.2%,1.23%,1.39%and 1.12%,and the maximum deviation of Vmean in the heart was 63.85 cGy,and the maximum deviation of Dmax in the spinal-cord was 70.78 cGy.There were statistically significant differences in the actual CP number(CPs),execution time(DT)of plan,and ratio value of machine unit(MU)of the complexity of plan to CPs(MU/CPs)among the plans of 9 groups(F=2.857,25.145,135.467,P<0.05),respectively.Conclusion:In the dIMRT plan of esophageal cancer of middle and lower segment,the maximum CP value is set at between 40-50,which can reduce the optimization time of the plan,the number of subfields and the treatment time of patients under the premise of meeting the dose of the target region and the OAR.
3.Regulatory effect of Epimedium flavonoid microparticles on pulmonary pre-metastatic microenvironment.
Xiao-Yu CHE ; Meng-Ting XU ; Ya-Qin LI ; Wen-Jing CHEN ; Yu-Ping LIU ; Yan CHEN
China Journal of Chinese Materia Medica 2024;49(21):5856-5864
Tumor metastasis is the main cause of death in clinical patients. The proposal of the pre-metastatic microenvironment hypothesis offers a new research direction for tumor metastasis. Targeting and inhibiting the activation of the stimulator of interferon genes(STING) signals by tumor cell-derived microparticles may help reduce tumor metastasis. This study constructed a pre-metastatic microenvironment and pulmonary metastasis model using recombinant adeno-associated virus vector-mediated short hairpin RNA interference of STING(rAAV STING shRNA) to investigate the effects of STING interference on the pre-metastatic microenvironment and the impact of total Epimedium flavonoids(EFs) as an intervention. Drug-containing microparticles were prepared by incubating mouse Lewis lung cancer(LLC) cells with the total EFs(EFs-LLC-MPs), and EFs-LLC-MPs were characterized by measuring the average particle size, polydispersity index, zeta potential, and release profile. Western blot was used to examine changes in pre-metastatic microenvironment markers in mouse alveolar epithelial cells(MLE-12) after treatment with microparticles or total EFs. Drug loading capacity and the uptake of microparticles by MLE-12 and mouse alveolar macrophages(MH-S) cells were determined using HPLC and flow cytometry. The uptake experiments showed that after nasal administration of rAAV STING shRNA, STING expression was significantly inhibited, and the markers of the pre-metastatic microenvironment were markedly reduced. Micro-CT results indicated a reduction in lung metastases and nodules, and the anti-metastatic effect of total EFs was affected. The results showed that the microparticles were membrane vesicles with a particle size of(373.17±3.18)nm, a Zeta potential of(-35.40±1.08)mV, a protein concentration of 562.62 μg·mL~(-1), and a drug loading of 0.060 9 μg per microgram of protein. These microparticles were effectively taken up by MLE-12 and MH-S cells. Treatment of MLE-12 and MH-S cells with EFs-LLC-MPs reduced the expression of pre-metastatic microenvironment markers such as fibronectin and lysyl oxidase(LOX). Based on these findings, it was confirmed that STING was involved in the regulation of the formation of the pre-metastatic microenvironment in the lungs. Furthermore, total EFs microparticles were successfully prepared, showing potential to intervene in the inflammatory pre-metastatic microenvironment, which could be promising for controlling tumor metastasis.
Animals
;
Flavonoids/chemistry*
;
Mice
;
Tumor Microenvironment/drug effects*
;
Epimedium/chemistry*
;
Lung Neoplasms/metabolism*
;
Humans
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Mice, Inbred C57BL
;
Neoplasm Metastasis
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Cell Line, Tumor
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Particle Size
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Drugs, Chinese Herbal/pharmacology*
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Membrane Proteins/metabolism*
4.Food security and diet quality among urban poor adolescents in Kuala Lumpur, Malaysia
Janice Ee Fang TAY ; Satvinder KAUR ; Wui Wui THAM ; Wan Ying GAN ; Nik Norasma CHE YA ; Choon Hui TAN ; Serene En HUI TUNG
Nutrition Research and Practice 2023;17(2):269-283
BACKGROUND/OBJECTIVES:
This study aimed to examine the food security status of urban poor adolescents and its association with diet quality.
SUBJECTS/METHODS:
A cross-sectional survey was conducted among 188 adolescents aged 13–18 yrs living in Kuala Lumpur, Malaysia. Household food insecurity and dietary intake data were collected using the Radimer/Cornell hunger and food insecurity instrument and 2-day 24-h dietary recalls, respectively. Diet quality was determined using the Malaysian Healthy Eating Index (HEI). Weight and height were measured and body mass index-for-age, as well as height-for-age z scores were calculated.
RESULTS:
The present study revealed that 47.9% of the adolescents experienced household food insecurity, 24.5% experienced individual food insecurity, 18.6% household food security, and 9.0% child hunger. The mean score of diet quality was 56.83 ± 10.09, with a significantly lower HEI score among food insecure adolescents (household food insecure, individual food insecure, and child hunger) than household food secure adolescents (P = 0.001). The differences between food secure and food insecure households were found to be significant for energy (P = 0.001) and nutrients including proteins (P = 0.006), carbohydrates (P = 0.005), dietary fiber (P = 0.001), folate (P < 0.001), and vitamin C (P = 0.006). The multiple linear regression showed that adolescents who experienced food insecurity (β = −0.328; P = 0.003) were found to be significantly associated with poor diet quality (F = 2.726; P < 0.01), wherein 13.3% of the variation in the diet quality was explained by the food security status.
CONCLUSIONS
Experiencing food insecurity contributed to poor diet quality among urban poor adolescents. Further longitudinal studies are needed to comprehensively understand this association to improve food insecurity and diet quality among urban poor communities.
5. Effect of corilagin on cholesterol metabolism in macrophages and its mechanism
Xin DENG ; Da MENG ; Jing-Yi WU ; Bing-Tong JIANG ; Ya-Qiong ZHANG ; Yi ZHAO ; Feng HUANG ; Yan-Yun CHE ; Yi-Yang YANG
Chinese Pharmacological Bulletin 2023;39(9):1696-1704
Aim To elucidate the effect of corilagin (Cor) on cholesterol metabolism in macrophages and the underlying mechanism. Methods Molecular docking was applied to predict the protein target of Cor on cellular cholesterol metabolism. The RAW264.7 macrophage foam model induced by 80 mg • L
6.Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis
Che-Sheng CHU ; Shu-Li CHENG ; Ya-Mei BAI ; Tung-Ping SU ; Shih-Jen TSAI ; Tzeng-Ji CHEN ; Fu-Chi YANG ; Mu-Hong CHEN ; Chih-Sung LIANG
Psychiatry Investigation 2023;20(9):861-869
Objective:
Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk.
Methods:
This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate.
Results:
With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3.
Conclusion
Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.
7.Progress in research on pyroptosis and its role in hepatocellular carcinoma
CHANG Yu⁃ling ; NIU Ya⁃qian CHEN Che
Chinese Journal of Biologicals 2023;36(1):124-127
Abstract:Pyroptosis is a new programmed cell death mode,which plays a dual role in the pathogenesis of hepatocellular
carcinoma(HCC). On the one hand,inflammasomes causing pyroptosis and inflammatory mediators released during cell
pyroptosis promote the occurrence and development of HCC;On the other hand,pyroptosis can inhibit the proliferation,
metastasis and invasion of HCC cells. With the deepening of research,the role of pyroptosis in HCC has become increasingly
prominent. This paper reviews the potential effects of pyroptosis on the progression of HCC and its role in anticancer therapy.
Keywords:Pyroptosis;Inflammasome;Hepatocellular carcinoma(HCC);Gasdermin D(GSDMD)
8.Occupational protection effect of two protective devices for manual cleaning and oiling of dental handpieces on operators.
Meng HAN ; Zhi Yu SHAO ; Li Na YIN ; Ya Qiang CHE ; Li Xin QIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(6):463-466
Objective: To explore the occupational protective effect of different protective devices on the operators during manual cleaning and oiling of dental handpieces, and to provide a basis for the selection of appropriate protective methods. Methods: From November 2020 to December 2021, 20 high-speed dental handpieces of the same brand were selected and randomly divided into disposable protective bag group and small aerosol safety cabinet group by drawing lots, with 10 in each group. After recording the model, they were distributed to the clinical fixed consulting room for use, and were collected by specially-assigned personnel every day for manual cleaning under the protection of the two devices. By measuring the number of airborne colonies, the concentrations of particulate matter and the satisfaction of operators, the occupational protection effect of the two protective devices on operators was evaluated. Results: Under the protection of the two devices, the average number of airborne colonies after operation was less than 1 CFU/ml. When no protective device was used, the number concentration of particulate matter produced during operation was (21595.70±8164.26) pieces/cm(3). The number concentrations of particles produced by disposable protective bag group [ (6800.24±515.05) pieces/cm(3)] and small aerosol safety cabinet group [ (5797.15±790.50) pieces/cm(3)] were significantly lower than those without any protective device (P<0.001). The number concentration of particle matter of small aerosol safety cabinet group was significantly lower than that of disposable protective bag group (P<0.001). In the satisfaction evaluation of operators, small aerosol safety cabinet group [ (3.53±0.82) points] was significantly better than disposable protective bag group [ (2.23±1.10) points] (P<0.001) . Conclusion: The use of small aerosol safety cabinet during manual cleaning and oiling of dental handpieces has good protective effect, superior safety performance and strong clinical applicability, and has advantages in occupational protection of clinical operators.
Aerosols
;
Particulate Matter
;
Protective Devices
9.Effect of exercise intervention on musculoskeletal disorders in nursing staff.
Xin JIANG ; Shuang Feng ZHENG ; Xuan Xuan YANG ; Anniwa REZI WANGULI ; Ya Jie CHE ; Ping YAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(9):677-681
Objective: To evaluate the effects of exercise intervention on musculoskeletal disorders (MSD) in nursing staff. Methods: In september 2021, we searched the articles on exercise intervention for nurses with musculoskeletal diseases in Embase, PubMed, ClinicalTrails, Wanfang, CNKI and other databases in September 2021, and the search period was from database creation to August 2021. The quality of article was evaluated by Cochrane bias risk assessment tool and MINORS. The systematic review method with narrative synthesis was used to analyze the research results. Results: A total of 7 studies were included, including 6 randomized controlled trials and 1 quasi-experiment. The sample size of the experimental group was 276, and the control group was 273. Depending on the type of exercise intervention, muscle strength training, muscle strength training+stretch/flexibility training, Back School program can reduce the local pain of nursing staff. Among them, muscle strength training can improve the nursing staff's muscle function and quality of life, muscle strength training+stretching/flexibility training can increase muscle strength, range of physical activity and self-efficacy, the Back School program is effective for improving poor posture. Conclusion: Exercise intervention is effective on controlling musculoskeletal disorder symptoms in nursing staff, managers can develop exercise strategies for different MSD symptoms.
Exercise Therapy/methods*
;
Humans
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Muscle Strength/physiology*
;
Musculoskeletal Diseases
;
Nursing Staff
;
Quality of Life
10.One case of rhabdomyolysis caused by acute phoxim poisoning.
Jia Ning WANG ; Che WANG ; Jun WANG ; Yong Xin SONG ; Ya Ping HE ; Zhao Xin LU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(10):782-784
Patients with organophosphate poisoning usually die from respiratory depression and respiratory failure. The incidence of rhabdomyolysis is relatively low, but the mortality rate is extremely high once it occurs. In this paper, the treatment of a patient with acute phoxim poisoning was analyzed. The patient developed severe rhabdomyolysis syndrome on the 3rd day of treatment, the creatine kinase exceeded the normal value by more than 300 times (up to 103510.65 U/L) , and renal failure occurred. Clinical treatment included active detoxification, blood purification, organ support, and internal environment maintenance. The patient's rhabdomyolysis continued, and the condition worsened. Finally, the family gave up the treatment and the patient died. It is suggested that attention should be paid to the occurrence of rhabdomyolysis syndrome during the treatment of organophosphorus poisoning, and timely blood purification technology may be the key to treatment.
Humans
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Rhabdomyolysis/chemically induced*
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Organothiophosphorus Compounds
;
Creatine Kinase
;
Incidence
;
Acute Kidney Injury


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