1.Puerarin attenuated ischemia/reperfusion injury an in vitro model through a repression of autophagy by HMGB1/TLR4/NF-κB axis
Yichen FAN ; Jiayi YAN ; Xueling LI ; Ni LIU ; Youhua ZHU ; Mingxing SUI ; Yifei ZHONG
Chinese Journal of Organ Transplantation 2021;42(9):549-553
Objective:To explore the protective effect of puerarin on hypoxia/reoxygenation (H/R)-induced acute kidney injury(AKI)in vitro.Methods:HK-2 cells were treated with H/R for simulating ischemia reperfusion injury(IRI)in vivo. The experimental groups included control group, H/R treatment group(0/6/12/24 h), H/R 24 h + puerarin treatment group(puerarin, Pue), H/R 24 h + Pue+ 3-methyladenine(3-MA)treatment group and H/R 24 h+ 3-MA treatment group. Immunoblotting was employed for detecting the expression changes of autophagy-related proteins, CCK-8 for examining cell proliferation, electron microscopy for observing autophagosome formation and TUNEL for detecting apoptosis.Results:As compared with control group, the expression of LC3-II rose in H/R 24 h group, the expression of autophagy marker P62 declined, count of autophagosome increased, cell viability decreased and cellular inflammation occurred. Puerarin had similar effects to 3-MA. As compared with H/R 24 h group, puerarin could reverse the changes in the expression levels of LC3 and P62 induced by H/R( P<0.05). There were greater cell viability, reduced autophagosome count and lessened cell apoptosis( P<0.05). At the same time, protein expression levels of HMGB1, TLR4 and NF-κB dropped( P<0.05). Conclusions:Puerarin suppresses autophagy through HMGB1/TLR4/NF-κB axis for lessening ischemia-reperfusion injury an in vitro model.
2.The value of peripheral blood component of T cells and neutrophil to lymphocyte ratio in thyroid cancer coexisted with Hashimoto’s thyroiditis
Cuizhong WANG ; Tong SHEN ; Yichen ZHONG ; Dexuan CHEN ; Zhaoqun MA ; Haijian SUN
Chinese Journal of Endocrine Surgery 2021;15(4):358-361
Objective:To evaluate clincal value of preoperative peripheral blood CD4/CD8 and neutrophil to lymphocyte ratio (NLR) in papillary thyroid carcinoma (PTC) coexisted with Hashimoto’s thyroiditis (HT) .Methods:Clinicopathological data of 202 patients diagnosed as PTC treated with operation from Jul.2016 to Jun.2019 were retrospectively analyzed. They were divided into Treatment Group including 94 PTC coexisted with HT and Control Group including 108 thyroid cancer according to the postoperateive pathology report. CD4+ and CD8+ subsets in peripheral blood were analyzed by flowcytometer and blood counts were measured before surgery.Results:There was no significant difference in gender, tumor size, number of lesions or lymph node metastasis between the two goups. In comparison with Control Group, median age was lower (39.5 vs 50.5, P=0.001) and CD4/CD8 raito (1.9731.973 Cvs 1.24141973 CD P=0.001) was higher in Treatment group. There was a higher proportion of bilateral lobe thyroidectomy in Treatment Group (40/94 vs 26/108, P=0.005) . A multivariate model analysis identified CD4/CD8 raito as independent risk factor for incidence of PTC coexisted with HT [ OR=0.035, 95% CI (0.009-0.093) , P=0.001]. The NLR level of thyroid cancer patients was correlated with lateral lymph node metastasis negatively (correlation coefficients=-0.286, P=0.045) . Conclusions:PTC might have some connection with HT mediated by body inmune status. Preoperative NLR level is correlated with lateral lymph node metastasis.
3.Disability-adjusted life years and the trends of the burden of colorectal cancer: a population-based study in Shanghai, China during 2002 to 2016
Wei ZHONG ; Liping CHEN ; Xiaopan LI ; Yichen CHEN ; Yao ZHANG ; Canjie GUO ; Yufeng SHEN ; Huimin CHEN
Chinese Medical Journal 2022;135(24):2950-2955
Background::Colorectal cancer (CRC) still ranks the top in morbidity and mortality of cancers worldwide, posing a huge threat and burden to the society. We aimed to determine the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) of CRC and explore potential changes in the temporal trends of the CRC burden in Shanghai during 2002 to 2016.Methods::The cancer statistics and demographics were obtained from the Cancer Registry and the Statistics Bureau of Pudong New Area, respectively. Data from 2002 to 2016 were included and analyzed retrospectively. DALYs were calculated using DisMod and the age-standardized rates (ASRs) were obtained according to Segi world standard population. Joinpoint regression was used to measure the trends in CRC incidence and to estimate the annual percent change.Results::The increasing trend of CRC ASR incidence halted after 2014, coinciding with the introduction of the Shanghai CRC screening program. The ASRs of mortality and DALYs increased, at 0.42% ( P < 0.05) and 4.07% ( P < 0.001) per year, respectively, which were mainly driven by men and individuals aged above the CRC screening program target. Conclusions::The disease burden of CRC in Shanghai remains serious, especially among men, and individuals aged >74 years. The benefits of the screening program have been partially proven by the ASRs of CRC incidence, providing important insights into better and wider application of screening programs.
4.mRNA delivery in cancer immunotherapy.
Yichen ZHONG ; Shi DU ; Yizhou DONG
Acta Pharmaceutica Sinica B 2023;13(4):1348-1357
Messenger RNA (mRNA) has drawn much attention in the medical field. Through various treatment approaches including protein replacement therapies, gene editing, and cell engineering, mRNA is becoming a potential therapeutic strategy for cancers. However, delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake. Therefore, in addition to mRNA modification, efforts have been devoted to developing nanoparticles for mRNA delivery. In this review, we introduce four categories of nanoparticle platform systems: lipid, polymer, lipid-polymer hybrid, and protein/peptide-mediated nanoparticles, together with their roles in facilitating mRNA-based cancer immunotherapies. We also highlight promising treatment regimens and their clinical translation.
5.MiR-22-3p targets gasdermin D to inhibit homocysteine-induced pyroptosis of vascular smooth muscle cells
Yingyi ZHONG ; Ning DING ; Yichen WANG ; Chao LIU ; Zhifeng DONG ; Shengchao MA ; Jiantuan XIONG ; Yinju HAO ; Zhigang BAI ; Yideng JIANG
Chinese Journal of Comparative Medicine 2024;34(9):12-18
Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells(VSMCs)induced by homocysteine(Hcy).Methods Human VSMCs were cultured in vitro and divided into a Control group(0 μmol/L Hey)and a Hey group(100 μmol/L Hey).After intervention,expression levels of pro Caspase-1,gasdermin D(GSDMD),N-GSDMD,and NLR family pyrin domain containing 3(NLRP3)were detected by Western blot.MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction.Interleukin(IL)-1 β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay.Cells were also transfected with control miR-22-3p(miR-22-3p-NC),miR-22-3p-mimic,and miR-22-3p-inhibitor,to observe the effects on VSMC pyroptosis induced by Hcy.Results Expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs were increased(P<0.05),IL-1 β and IL-18 levels were increased(P<0.01),and the relative expression level of miR-22-3p was reduced(P<0.01)in the Hcy group compared with the Control group.Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P<0.01),and significantly decreased levels of IL-1β and IL-18(P<0.01),while transfection with miR-22-3p-inhibitor significantly increased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P<0.01)and significantly increased the levels of IL-1β and IL-18(P<0.05).Conclusions MiR-22-3p may delay Hcy-induced VSMC pyroptosis.