1.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
2.Morphological classification and molecular identification of Hyalomma asiaticum in parts of Xindi Township,Xinjiang
Xiao-Qing ZAN ; Qiao-Yun REN ; Jin LUO ; Yan-Long WANG ; Pei-Wen DIAO ; Li-Yan CHE ; Jian-Xun LUO ; Hong YIN ; Gui-Quan GUAN ; Guang-Yuan LIU ; Hong-Xi ZHAO
Chinese Journal of Zoonoses 2024;40(4):289-294
The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.
3.Advances in the association between Helicobacter pylori infection and non-alcoholic fatty liver disease as well as its potential mechanisms
Guang-Yao ZHAO ; Long-Yun WU ; Qiao-Yun XIA ; Xiao-Lan LU
Fudan University Journal of Medical Sciences 2024;51(6):1002-1008
Helicobacter pylori(HP),a well-established carcinogenic factor,is implicated in the pathogenesis of gastric ulcer,gastric cancer,and other related diseases.Recent studies have unveiled a significant association between HP infection and an increased prevalence of non-alcoholic fatty liver disease(NAFLD).Furthermore,it has been observed that eradication of HP can ameliorate metabolic disorders and relieve NAFLD.Some studies have explored the possible mechanism,which may be related to energy metabolism disorder and gut microbiota imbalance caused by HP.This review outlined the current research status regarding the association between HP and NAFLD,as well as elucidated the potential mechanisms through which HP promoted the onset and progression of NAFLD.
4.Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (Ⅱ): classification of tablets disintegration behavior.
Xiao-Qing ZHAO ; Dong-Ling LIAO ; Fei-Yu QI ; Zi-Chen LIANG ; Xue-Fang TANG ; Sheng-Yun DAI ; Yan-Jiang QIAO ; Bing XU
China Journal of Chinese Materia Medica 2023;48(12):3180-3189
In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.
Commerce
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Medicine, Chinese Traditional
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Tablets
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Water
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Drug Compounding
5.Herbal-moxa plaster for diarrhea type irritable bowel syndrome of spleen and kidney yang deficiency: a randomized controlled trial.
Zheng-Rong ZHAO ; Ya-Xuan WANG ; Fang-Yuan XU ; Wen-Chao ZHANG ; Qiao-Yun WANG ; Wei HUANG
Chinese Acupuncture & Moxibustion 2023;43(6):617-621
OBJECTIVE:
To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency.
METHODS:
Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24+), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated.
RESULTS:
Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05).
CONCLUSION
On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.
Humans
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Spleen
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Irritable Bowel Syndrome/drug therapy*
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Quality of Life
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Yang Deficiency/drug therapy*
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Kidney
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Diarrhea
6. The protective effect of orcinol glucoside on dexamethasone induced osteoblast cell damage through inhibition of glucocorticoid receptor nucleus translocation
Xin-Yun-Xi HE ; Wan-Lu ZHAO ; Yang YU ; Yan LIU ; Qiao-Yan ZHANG ; Quan-Long ZHANG ; Lu-Ping QIN
Chinese Pharmacological Bulletin 2023;39(7):1346-1353
Aim To investigate the protective effect of orcinol glucoside on dexamethasone(DEX)-induced osteoblast injury and its mechanism. Methods Primary osteoblasts were extracted from calvaria of neonatal mice and cultured in medium with DEX(1 μmol•L
7.Neuropsychological development of large for gestational age infants at the age of 12 months.
Meng-Yu BAO ; Xiu-Yun QIAO ; Xin-Han ZHANG ; Zi-Xuan ZHANG ; Fei ZHAO ; Xin-Xia CHEN
Chinese Journal of Contemporary Pediatrics 2023;25(12):1246-1252
OBJECTIVES:
To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months.
METHODS:
The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age.
RESULTS:
After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05).
CONCLUSIONS
The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.
Infant, Newborn
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Infant
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Child
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Humans
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Birth Weight
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Infant, Large for Gestational Age
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Infant, Small for Gestational Age
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Gestational Age
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Child Health
8.Comprehensive analysis of RNA-seq and whole genome sequencing data reveals no evidence for SARS-CoV-2 integrating into host genome.
Yu-Sheng CHEN ; Shuaiyao LU ; Bing ZHANG ; Tingfu DU ; Wen-Jie LI ; Meng LEI ; Yanan ZHOU ; Yong ZHANG ; Penghui LIU ; Yong-Qiao SUN ; Yong-Liang ZHAO ; Ying YANG ; Xiaozhong PENG ; Yun-Gui YANG
Protein & Cell 2022;13(5):379-385
9.Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques.
Chun-Chun GAO ; Man LI ; Wei DENG ; Chun-Hui MA ; Yu-Sheng CHEN ; Yong-Qiao SUN ; Tingfu DU ; Qian-Lan LIU ; Wen-Jie LI ; Bing ZHANG ; Lihong SUN ; Si-Meng LIU ; Fengli LI ; Feifei QI ; Yajin QU ; Xinyang GE ; Jiangning LIU ; Peng WANG ; Yamei NIU ; Zhiyong LIANG ; Yong-Liang ZHAO ; Bo HUANG ; Xiao-Zhong PENG ; Ying YANG ; Chuan QIN ; Wei-Min TONG ; Yun-Gui YANG
Protein & Cell 2022;13(12):920-939
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals
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COVID-19/genetics*
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Macaca mulatta
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SARS-CoV-2/genetics*
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Transcriptome
10.Investigation on influenza vaccination policy and vaccination situation during the influenza seasons of 2020-2021 and 2021-2022 in China.
Hong Ting ZHAO ; Zhi Bin PENG ; Zhao Lin NI ; Xiao Kun YANG ; Qiao Yun GUO ; Jian Dong ZHENG ; Ying QIN ; Yan Ping ZHANG
Chinese Journal of Preventive Medicine 2022;56(11):1560-1564
Objective: To investigate the policies and coverage of influenza vaccine during the influenza epidemic seasons of 2020-2021 and 2021-2022 in China. Methods: The national influenza vaccination policy and vaccination rate were investigated in counties and districts and described in the two epidemic seasons. Results: In the epidemic seasons of 2020-2021 and 2021-2022, the vaccination coverage of influenza in China was 3.16% and 2.47%, respectively. The free vaccination policy had the highest vaccination coverage (51.75% and 38.32%), followed by the medical insurance reimbursement policy (9.74% and 7.36%). During the epidemic season of 2021-2022, the number of counties and districts implementing the free vaccination policy in China decreased 61 compared with the previous year, but the number of people covered increased by 51.29%. However, the vaccination coverage of the vast population decreased significantly, with the medical staff (75.69% and 40.15% for two epidemic seasons), preschool children (58.86% and 26.15%), and the elderly (45.71% and 32.94%). During the epidemic season of 2021-2022, the number of counties and districts implementing the medical insurance reimbursement policy increased by 6 compared with the previous year, and the number of people covered increased by 11.12%, but the vaccination coverage decreased. Conclusion: The influenza vaccination rate in China is low, and the implementation of cost preferential policy can greatly improve the influenza vaccination rate.
Child, Preschool
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Humans
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Aged
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Influenza, Human/prevention & control*
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Seasons
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Influenza Vaccines
;
Vaccination
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China/epidemiology*
;
Policy

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