Insulin Resistance Reduces Sensitivity to Cis-Platinum and Promotes Adhesion, Migration and Invasion in HepG2 Cells

Li, Lin-Jing,Li, Guang-Di,Wei, Hu-Lai,Chen, Jing,Liu, Yu-Mei,Li, Fei,Xie, Bei,Wang, Bei,Li, Cai-Li Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.

Ebb-and-Flow of Macroautophagy and Chaperone-Mediated Autophagy in Raji Cells Induced by Starvation and Arsenic Trioxide

Li, Cai-Li,Wei, Hu-Lai,Chen, Jing,Wang, Bei,Xie, Bei,Fan, Lin-Lan,Li, Lin-Jing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Autophagy is crucial in the maintenance of homeostasis and regenerated energy of mammalian cells. Macroautophagy and chaperone-mediated autophagy(CMA) are the two best-identified pathways. Recent research has found that in normal cells, decline of macroautophagy is appropriately parallel with activation of CMA. However, whether it is also true in cancer cells has been poorly studied. Here we focused on cross-talk and conversion between macroautophagy and CMA in cultured Burkitt lymphoma Raji cells when facing serum deprivation and exposure to a toxic compound, arsenic trioxide. The results showed that both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of nutrition deprivation, and then gradually decreased to near baseline. With nutrient deprivation persisted, CMA progressively increased along with the decline of macroautophagy. On the other hand, in arsenic trioxide-treated Raji cells, macroautophagy activity was also significantly increased, but CMA activity was not rapidly enhanced until macroautophagy was inhibited by 3-methyladenine, an inhibitor. Together, we conclude that cancer cells exhibit differential responses to diverse stressor-induced damage by autophagy. The sequential switch of the first-aider macroautophagy to the homeostasis-stabilizer CMA, whether active or passive, might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular stressors. These findings must be helpful to understand the characteristics, compensatory mechanisms and answer modes of different autophagic pathways in cancer cells, which might be very important and promising to the development of potential targeting interventions for cancer therapies via regulation of autophagic pathways.

BMB Reports : Nutlin-3 downregulates p53 phosphorylation on serine and induces apoptosis in hepatocellular carcinoma cells

( Xin Li Shi ),( Jing Li Liu ),( Lai Feng Ren ),( Nan Mao ),( Fang Tan ),( Nana Ding ),( Jing Yang ),( Ming Yuan Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.4

Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical application for the human hepatocellular carcinoma (HCC) treatment. The reactivation of p53 is an attractive therapeutic strategy in cancer with disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in various cancers. The post-translational modifications of p53 are a hot topic, but there are some controversy ideas about the function of phospho-Ser392-p53 protein in cancer cell lines in response to Nutlin-3. Therefore, we investigated the relationship between Nutlin-3 and phospho-Ser392-p53 protein expression levels in SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that Nutlin-3 induced apoptosis through down-regulation phospho-Ser392-p53 in two HCC cells. The result suggests that inhibition of p53 phosphorylation on Ser392 presents an alternative for HCC chemotherapy. [BMB Reports 2014; 47(4): 221-226]

The triply periodic minimal surface-based 3D printed engineering scaffold for meniscus function reconstruction

Lan Li,Peng Wang,Jing Jin,Chunmei Xie,Bin Xue,Jiancheng Lai,Liya Zhu,Qing Jiang 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: The meniscus injury is a common disease in the area of sports medicine. The main treatment for this disease is the pain relief, rather than the meniscal function recovery. It may lead to a poor prognosis and accelerate the progression of osteoarthritis. In this study, we designed a meniscal scaffold to achieve the purposes of meniscal function recovery and cartilage protection. Methods: The meniscal scaffold was designed using the triply periodic minimal surface (TPMS) method. The scaffold was simulated as a three-dimensional (3D) intact knee model using a finite element analysis software to obtain the results of different mechanical tests. The mechanical properties were gained through the universal machine. Finally, an in vivo model was established to evaluate the effects of the TPMS-based meniscal scaffold on the cartilage protection. The radiography and histological examinations were performed to assess the cartilage and bony structures. Different regions of the regenerated meniscus were tested using the universal machine to assess the biomechanical functions. Results: The TPMS-based meniscal scaffold with a larger volume fraction and a longer functional periodicity demonstrated a better mechanical performance, and the load transmission and stress distribution were closer to the native biomechanical environment. The radiographic images and histological results of the TPMS group exhibited a better performance in terms of cartilage protection than the grid group. The regenerated meniscus in the TPMS group also had similar mechanical properties to the native meniscus. Conclusion: The TPMS method can affect the mechanical properties by adjusting the volume fraction and functional periodicity. The TPMS-based meniscal scaffold showed appropriate features for meniscal regeneration and cartilage protection.

China Consensus Document on Allergy Diagnostics

Chen Hao,Li Jing,Cheng Lei,Gao Zhongshan,Lin Xiaoping,Zhu Rongfei,Yang Lin,Tao Ailin,Hong Haiyu,Tang Wei,Guo Yinshi,Huang Huaiqiu,Sun Jinlyu,Lai He,Lei Cheng,Liu Guanghui,Xiang Li,Chen Zhuanggui,Ma Ha 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.2

The prevalence of allergic diseases has increased dramatically in recent years in China, affecting the quality of life in 40% of the population. The identification of allergens is the key to the diagnosis of allergic diseases. Presently, several methods of allergy diagnostics are available in China, but they have not been standardized. Additionally, cross-sensitization and co-sensitization make allergy diagnostics even more complicated. Based on 4 aspects of allergic disease (mechanism, diagnosis procedures, allergen detection in vivo and in vitro as well as the distribution map of the most important airborne allergens in China) and by referring to the consensus of the European Society of Allergy and Clinical Immunology, the World Allergy Organization, and the important literature on allergy diagnostics in China in recent years, we drafted this consensus of allergy diagnostics with Chinese characteristics. It aims to standardize the diagnostic methods of allergens and provides a reference for health care givers. The current document was prepared by a panel of experts from the main stream of professional allergy associations in China.

Astragalus polysaccharide: a review of its immunomodulatory effect

Chun-xiao Li,Ying Liu,Yu-zhen Zhang,Jing-chun Li,Jiang Lai 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.6

The Astragalus polysaccharide is an importantbioactive component derived from the dry root of Astragalusmembranaceus . This review aims to provide a comprehensiveoverview of the research progress on the immunomodulatoryeff ect of Astragalus polysaccharide and providevaluable reference information. We review the immunomodulatoryeff ect of Astragalus polysaccharide on central andperipheral immune organs, including bone marrow, thymus,lymph nodes, spleen, and mucosal tissues. Furthermore, theimmunomodulatory eff ect of Astragalus polysaccharide on avariety of immune cells is summarized. Studies have shownthat Astragalus polysaccharide can promote the activities ofmacrophages, natural killer cells, dendritic cells, T lymphocytes,B lymphocytes and microglia and induce the expressionof a variety of cytokines and chemokines. The immunomodulatoryeff ect of Astragalus polysaccharide makesit promising for the treatment of many diseases, includingcancer, infection, type 1 diabetes, asthma, and autoimmunedisease. Among them, the anticancer effect is the mostprominent. In short, Astragalus polysaccharide is a valuableimmunomodulatory medicine, but further high-qualitystudies are warranted to corroborate its clinical effi cacy.

Chinese herbal medicine (Rupi Sanjie capsule) for the treatment of breast pain: A systematic review and meta-analysis of randomized clinical trials

Bao-yong Lai,Li-yan Jia,Bo-Wen Yu,Shi-Bing Liang,Ai-Jing Chu,Hui-juan Cao,Jian-ping Liu,Xiao-Hua Pei 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.2

Background: Breast pain is one of the most common breast disorders, affecting 41%–69% women in the clinical populations. Chinese herbal medicine (Rupi Sanjie, RPSJ) capsule has been recommended to be commonly used for breast pain in China. This review aimed to systematically collect latest evidence and critically evaluate the eff ;ectiveness and safety of RPSJ capsule for breast pain. Methods: We searched 6 databases from their inception to June 1, 2020 for randomized clinical trials (RCTs) comparing RPSJ capsule with conventional drug therapies, placebo or no treatment. Primary outcomes were breast pain relief, reduction of breast mass and clinical cure rate. Results: Seventeen RCTs were included in total, involving 2899 participants with breast pain. RPSJ capsule showed a significant effects in shortening duration of the breast pain (MD-6.51 days, 95%CI [-8.57, -4.45], n = 82, 1 trial), shortening the duration of breast mass (MD-5.17 days, 95%CI [-7.56, -2.78], n = 82, 1 trial), improving clinical cure rate (RR 1.55, 95% CI [1.21, 2.00], I² = 64%, n = 1398, 10 trials) and total effective rate (RR 1.08, 95% CI [1.03, 1.14], I² = 71%, n = 2170, 14 trials) compared to Tamoxifen (TAM). The meta-analysis showed that the incidence of total adverse events was higher in TAM group than the RPSJ capsule group (RR 0.30, 95%CI [0.21, 0.42], I² = 49%, n = 2122, 13 trials). Conclusions: RPSJ capsule appears to be a potentially effective in treating breast pain and seems generally safe for clinical application. However, this potential benefit is inconclusive due to generally weak evidence, and the findings should be further confirmed in large and rigorous trials.

Low-dose diethylhexyl phthalate exposure does not impair the expressive patterns of epigenetics-related genes and DNA methylation of breast cancer-related genes in mouse mammary glands

Shun-Feng Cheng,Ling Li,Bo Li,Jing-Cai Liu,Fang-Nong Lai,Yong Zhao,Xi-Feng Zhang,Wei Shen,Lan Li 대한독성 유전단백체 학회 2018 Molecular & cellular toxicology Vol.14 No.2

Backgrounds: Di-(2-ethylhexyl) phthalate (DEHP), as an endocrine-disrupting chemical (EDC), is widely used in plasticizer and other productions. Ubiquitous human exposure to DEHP has been proposed to be a potential risk to public health. Developmental exposure to DEHP could alter epigenetic programming and result in adult-onset disease. Methods: In this study, we investigated whether DEHP exposure to pregnant mice affected epigenetic changes as a result of increase in breast cancer incidence. Results: Our results showed that the expression of total 143 epigenetics-related genes in mammary gland cells, have no significantly altered after short time and low-dose treated with DEHP from 0.5 days post-coitum (dpc) to 3.5 dpc of pregnant mice. DNA methylation status of some neoplastic development genes, such as EGFr, Esr1, Pgr, Fos and Rassf5 also had no obvious change. Conclusion: These finding showed no impact of DEHP on the expressive patterns of epigenetics-related genes and DNA methylation of breast cancer-related genes in pregnant mouse mammary gland cells.

The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65

Xichang Wang,Haoyu Wang,Li Yan,Lihui Yang,Yuanming Xue,Jing Yang,Yongli Yao,Xulei Tang,Nanwei Tong,Guixia Wang,Jinan Zhang,Youmin Wang,Jianming Ba,Bing Chen,Jianling Du,Lanjie He,Xiaoyang Lai,Yanbo Li 대한내분비학회 2021 Endocrinology and metabolism Vol.36 No.4

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure(BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosedaccording to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in femalesor subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP)were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely relatedwith SCH in female subjects aged <65 years. Conclusion: The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BPcomponents in females younger than 65 years.

Integrin α5β1-Ang1/Tie2 receptor cross-talk regulates brain endothelial cell responses following cerebral ischemia

Defang Pang,Lu Wang,Jing Dong,Xiaoyin Lai,Qijuan Huang,Richard Milner,Longxuan Li 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

We have previously demonstrated that in response to cerebral ischemia (CI), the growth factor angiopoietin-1 (Ang1) and α5β1 integrin are both induced in cerebral vessels, which likely provide positive signals driving the endogenous angiogenic response and vascular protection after CI. However, the precise relationship between endothelial Ang1 and α5β1 integrin after CI remains poorly understood. Here, we investigated the effects of the interaction between the Ang1/Tie2 system and α5β1 integrin on brain endothelial cells (BECs) under cerebral ischemic conditions in vivo and in vitro. Immunofluorescence analysis demonstrated that integrin α5β1 co-localized with Tie2/phosphorylated Tie2 on cerebral vessels in the penumbra. The in vitro study showed that oxygen–glucose deprivation/restoration (OGD/R) induced the expression of the Ang1 receptor Tie2 on BECs in a manner similar to that for integrin α5 and Ang1 in response to OGD/R, accompanied by increased activation of Tie2 and its downstream effectors focal adhesion kinase (FAK) and Akt. Knockdown of α5 integrin markedly suppressed OGD/R-induced Tie2 receptor activation in BECs, while in contrast, priming BECs with Ang1 promoted the expression of α5 integrin as well as the Tie2 downstream transcription factor Ets-1 in OGD-treated BECs. In line with this, Ets-1 knockdown significantly attenuated Ang1- mediated upregulation of α5 integrin. Functionally, Ang1 induced cell migration and tube formation of BECs after OGD, but this effect was inhibited by diminishment of the levels of α5 integrin in BECs. Taken together, our data indicate that the Ang1/Tie2 system cross-talks with integrin α5β1 in BECs after CI, which may contribute to the endogenous angiogenic vascular protective response following CI.