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.Effect of Wearing Phospholipid-releasing Contact Lenses on Dry Eyes in Rabbits
Hyeon Jung KIM ; Sehie PARK ; Yun Kyoung RYU ; Jin Sun HWANG ; Sun Hee OH ; Jae Hwi LEE ; Gui Bae KIM ; Young Joo SHIN
Journal of the Korean Ophthalmological Society 2025;66(4):181-190
Purpose:
To investigate whether a new phospholipid-releasing soft contact lens can improve symptoms of dry eyes.
Methods:
The study used 2.5-3.0 kg New Zealand rabbits including both normal non-dry eye rabbits and dry eye rabbits, the latter having undergone electrocauterization of the meibomian glands to block the gland orifices. Each rabbit wore a control contact lens on one eye and a phospholipid-releasing contact lens on the other eye daily. Phospholipid-releasing and control contact lenses were provided by NEOVISION Co., Ltd. The parameters assessed included tear film break-up time, tear osmolarity, ocular surface staining, and central corneal thickness. After the experiment, the rabbits were euthanized and their conjunctival tissue was stained with Periodic Acid Schiff (PAS) to observe conjunctival goblet cells.
Results:
In both dry eye and normal non-dry eye rabbits, tear film break-up time was longer and tear osmolarity was lower when using the phospholipid-releasing contact lens compared to the control contact lens. The ocular surface remained unstained in normal non-dry eye rabbits while staining was observed in dry eye rabbits. There was no significant difference in central corneal thickness between the control and phospholipid-releasing contact lenses in either group. PAS staining showed no difference in conjunctival goblet cell density between the two lens types in normal non-dry eye rabbits. However, in dry eye rabbits, the conjunctival goblet cell density tended to be slightly higher with the phospholipid-releasing contact lens compared to the control lens.
Conclusions
Phospholipid-releasing contact lenses may help reduce dry eye symptoms and minimize contact lens-related complications by stabilizing the tear film and lowering tear osmolarity.
3.Effect of Wearing Phospholipid-releasing Contact Lenses on Dry Eyes in Rabbits
Hyeon Jung KIM ; Sehie PARK ; Yun Kyoung RYU ; Jin Sun HWANG ; Sun Hee OH ; Jae Hwi LEE ; Gui Bae KIM ; Young Joo SHIN
Journal of the Korean Ophthalmological Society 2025;66(4):181-190
Purpose:
To investigate whether a new phospholipid-releasing soft contact lens can improve symptoms of dry eyes.
Methods:
The study used 2.5-3.0 kg New Zealand rabbits including both normal non-dry eye rabbits and dry eye rabbits, the latter having undergone electrocauterization of the meibomian glands to block the gland orifices. Each rabbit wore a control contact lens on one eye and a phospholipid-releasing contact lens on the other eye daily. Phospholipid-releasing and control contact lenses were provided by NEOVISION Co., Ltd. The parameters assessed included tear film break-up time, tear osmolarity, ocular surface staining, and central corneal thickness. After the experiment, the rabbits were euthanized and their conjunctival tissue was stained with Periodic Acid Schiff (PAS) to observe conjunctival goblet cells.
Results:
In both dry eye and normal non-dry eye rabbits, tear film break-up time was longer and tear osmolarity was lower when using the phospholipid-releasing contact lens compared to the control contact lens. The ocular surface remained unstained in normal non-dry eye rabbits while staining was observed in dry eye rabbits. There was no significant difference in central corneal thickness between the control and phospholipid-releasing contact lenses in either group. PAS staining showed no difference in conjunctival goblet cell density between the two lens types in normal non-dry eye rabbits. However, in dry eye rabbits, the conjunctival goblet cell density tended to be slightly higher with the phospholipid-releasing contact lens compared to the control lens.
Conclusions
Phospholipid-releasing contact lenses may help reduce dry eye symptoms and minimize contact lens-related complications by stabilizing the tear film and lowering tear osmolarity.
4.Effect of Wearing Phospholipid-releasing Contact Lenses on Dry Eyes in Rabbits
Hyeon Jung KIM ; Sehie PARK ; Yun Kyoung RYU ; Jin Sun HWANG ; Sun Hee OH ; Jae Hwi LEE ; Gui Bae KIM ; Young Joo SHIN
Journal of the Korean Ophthalmological Society 2025;66(4):181-190
Purpose:
To investigate whether a new phospholipid-releasing soft contact lens can improve symptoms of dry eyes.
Methods:
The study used 2.5-3.0 kg New Zealand rabbits including both normal non-dry eye rabbits and dry eye rabbits, the latter having undergone electrocauterization of the meibomian glands to block the gland orifices. Each rabbit wore a control contact lens on one eye and a phospholipid-releasing contact lens on the other eye daily. Phospholipid-releasing and control contact lenses were provided by NEOVISION Co., Ltd. The parameters assessed included tear film break-up time, tear osmolarity, ocular surface staining, and central corneal thickness. After the experiment, the rabbits were euthanized and their conjunctival tissue was stained with Periodic Acid Schiff (PAS) to observe conjunctival goblet cells.
Results:
In both dry eye and normal non-dry eye rabbits, tear film break-up time was longer and tear osmolarity was lower when using the phospholipid-releasing contact lens compared to the control contact lens. The ocular surface remained unstained in normal non-dry eye rabbits while staining was observed in dry eye rabbits. There was no significant difference in central corneal thickness between the control and phospholipid-releasing contact lenses in either group. PAS staining showed no difference in conjunctival goblet cell density between the two lens types in normal non-dry eye rabbits. However, in dry eye rabbits, the conjunctival goblet cell density tended to be slightly higher with the phospholipid-releasing contact lens compared to the control lens.
Conclusions
Phospholipid-releasing contact lenses may help reduce dry eye symptoms and minimize contact lens-related complications by stabilizing the tear film and lowering tear osmolarity.
5.One-stage posterior debridement and spinal internal fixation for the treatment of lumbar Brucellar spondylitis
Xian-Shuai KOU ; Wei SHE ; Gui-Fu MA ; Xing-Yu PU ; Yun-Biao WU ; Yang QI ; Wen-Yuan LUO
China Journal of Orthopaedics and Traumatology 2024;37(8):764-771
Objective To explore the clinical efficacy and safety of one-stage posterior lesion removal and internal spinal fixation in patients with lumbar Brucellosis spondylitis.Methods The clinical data of 24 patients admitted from October 2017 to October 2022 were retrospectively analyzed,2 patients were lost to follow-up at 10 months after surgery,at the final 22 cases were included in the study,including 13 males and 9 females with an average age of(52.00±6.89)years old,were treated with one-stage posterior lesion removal and internal spinal fixation.The operation time,intraoperative bleeding,follow-up time,ery-throcyte sedimentation rate(ESR)and C-reactive protein(CRP)before and after operation were recorded.The pain visual ana-logue scale(VAS),Oswestry disability index(ODI),the Japanese Orthopaedic Association(JOA)score for neurofunction,American Spinal Injury Association(ASIA)spinal cord injury grade and modified MacNab criteria were ussed to evaluate the efficacy.Results All patients were followed up from 12 to 30 months with an average of(17.41±4.45)months.The operation time was 70 to 155 min with an average of(1 16.59±24.32)min;the intraoperative bleeding volume was 120 to 520 ml with an average of(275.00±97.53)ml.CRP and ESR levels decreased more significantly at 1 week and at the final follow-up than pre-operative levels(P<0.05).VAS,JOA score and ODI at 1 week and at the latest follow-up were more significantly improved than preoperative results(P<0.05).There was no significant difference between ASIA preoperative and 1 week after operation(P>0.05),and a significant difference between preoperative and last follow-up(P<0.05).In the final follow-up,21 patients had ex-cellent efficacy,1 patient had fair,and there was no recurrence during the follow-up.Conclusion One-stage transpedicular le-sion removal and internal spinal fixation,with few incisions and short operation time,helps the recovery of neurological func-tion,and the prognosis meets the clinical requirements,which can effectively control Brucella spondylitis.
6.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.
7.Distribution Characteristics of Rh Phenotype and Feasibility of Compatible Blood Transfusion in Pregnant and Postpartum Women
Gui-Lin YANG ; Tao ZHANG ; Chun-Li LI ; Hong-Peng ZHANG ; Ying-Ying WU ; Sheng-Lan LI ; Kuai WAN ; Yun-Ping YANG
Journal of Experimental Hematology 2024;32(3):868-874
Objective:To analyze the distribution characteristics of Rh phenotype in pregnant and postpartum women in Chongqing area,and to explore the clinical significance of Rh phenotype in pregnant and postpartum women and the feasibility of Rh phenotype compatible blood transfusion.Methods:The ABO blood group and Rh phenotype of 65 161 pregnant and postpartum women were detected by microcolumn gel method,and 48 122 males in the same period were taken as controls.The data were analyzed by Chi-square test.Results:There were 112 870 cases(99.64%)of RhD+in 113 283 samples.In RhD+cases,CCDee(48.39%)and CcDEe(32.88%)were the main phenotypes.The first case of D--phenotype in Chongqing area was detected.413 cases(0.36%)of RhD-were detected,with ccdee(52.78%)and Ccdee(33.41%)as the main phenotypes.Compared with RhD-group,RhD+group showed statistically significant difference in Rh phenotype distribution(P<0.01).Among 65 161 maternal samples,the positive rate of 5 antigens of Rh blood group from high to low was D>e>C>c>E,and there was no significant difference compared with male samples(P>0.05).There was no significant difference in the distribution of Rh phenotype between males and pregnant/postpartum women,as well as between pregnant/postpartum women with different ABO blood groups(P>0.05).In pregnant and postpartum women,there was no significant difference in distribution of Rh phenotype among the normal pregnancy population,the population with adverse pregnancy history,the population using human assisted reproductive technology(ART)and the population with infertility(P>0.05).There was no significant difference in the distribution of Rh phenotype between the 4 populations mentioned above and the inpatients in the local general Grade A hospitals and the blood donors(P>0.05).In RhD positive pregnant and postpartum women,the probability of finding compatible blood for CcDEe phenotype was 100%,the probability of finding compatible blood for CCDee,CcDee and CCDEe phenotypes was 45%-60%,the probability of finding compatible blood for ccDEE,ccDEe and CcDEE phenotypes was 5%-10%,and the probability of finding compatible blood for other phenotypes was lower than 0.5%.The supply of blood with CCDee and ccDEE phenotypes can meet the compatible transfusions requirements of 7 Rh phenotypes in more than 99%of patients.Conclusion:Rh phenotype detection should be carried out for pregnant and postpartum women,and it is feasible to carry out Rh phenotype-matched or compatible blood transfusion for pregnant and postpartum women who need blood transfusion.
8.Curcumol Mediates the Programmed Cell Death in Acute Myeloid Leukemia through PI3K/AKT Signaling Pathway
Zuo-Tao LI ; Xiao-Yun CHEN ; Hai-Liang LI ; Gui-Xiang LENG ; Yan-Quan LIU ; Ling GUO ; Yi-Li WANG
Journal of Experimental Hematology 2024;32(6):1682-1688
Objective:To investigate the effects of Curcumol on the malignant biological characteristics of acute myeloid leukemia (AML)cells and its molecular mechanism,and to provide theoretical and experimental evidence for the anti-leukemia treatment of traditional Chinese medicine.Methods:After the AML cell lines HL-60 and KG-1 cells were treated different concentrations of with Curcumol.The proliferation activity of cells was detected by CCK-8 method,and the expression changes of apoptotic proteins and PI3 K/AKT signaling pathway proteins were detected by Western blot. Real-time quantitative fluorescence polymerase chain reaction (RT-qPCR ) was used to detect the expression of Caspase family mRNA.Results:Curcumol could inhibit the proliferation and induce apoptosis of HL-60 and KG-1 cells,promote apoptosis by up-regulating the expression of Bax and down-regulating the expression of Bcl-2 protein (P<0.05).When Curcumol interferes with HL-60 and KG-1 cells,it can also induce programmed cell death of AML by inhibiting PI3 K/AKT signaling pathway.In addition,after the intervention of Curcumol,the expression of Caspase 3,Caspase 6,Caspase 8 and Caspase 9 were up-regulated in HL-60 cells (P<0.05 ),the expression of Caspase 3,Caspase 8 and Caspase 9 were significantly up-regulated in KG-1 cells (P<0.01),while the expression of Caspase 6 was weakly affected (P<0.05 ),but low concentration of Curcumol (<60 μg/ml)had no effect on the expression of Caspase 6 in KG-1 cells (P>0.05).Conclusion:Curcumol may mediate the programmed death of AML cells by inhibiting the PI3K/AKT signaling pathway,affecting the expression of Bcl-2 family proteins,and promoting the activation of core members of Caspase family,so as to play an anti-leukemia role.
9.Consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma
Dai-Liang ZHANG ; Xin-Na DONG ; Lei SHI ; Xiao-Di DONG ; Yong-Qiang LIN ; Rong-Fei ZHANG ; Jing-Hua ZHANG ; Yuan-Cheng YAO ; Feng-Chao ZHANG ; Gui-Yun CAO ; Zhao-Qing MENG
Chinese Traditional Patent Medicine 2024;46(9):2851-2858
AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.
10.Research on provision standards and appropriateness of functional recovery training services in long-term care facilities: An exploratory mixed method study
Gui Yun CHOI ; Hye Kyung LEE ; Dukyoo JUNG ; Hasuk BAE ; Seoyon YANG ; Jongnyeo CHOI
Journal of Korean Gerontological Nursing 2024;26(3):322-331
This study was conducted to confirm the provision standards and appropriateness of functional recovery training services performed on residents in long-term care facilities. Methods: Twenty-eight service providers working in four long-term care facilities applied the functional recovery training services to 63 older residents for 15 days, integrating them with their existing daily tasks. The contents recorded by the service providers on checklists were analyzed, and the experiences of applying functional recovery training services by the service providers were examined through focus group interviews. Results: Training for activities of daily living, excluding bathing, five items such as dressing and undressing are performed 2 to 4 times per day. The duration for one session is approximately 16 minutes for meals, around 10 minutes for bathing, and about 5 to 7 minutes for the remaining activities. Movement and walking training, covering five items like standing, occurs 2 to 3 times per day, with session durations ranging from 3 to 10 minutes. Physical activity training is conducted 1 to 2 times per day, with each session lasting about 5 to 7 minutes. Cognitive activity training is performed 1 to 2 times per day, with each session lasting approximately 4 to 7 minutes. Conclusion: For functional recovery training to be established in long-term care facilities, it is crucial to share an accurate understanding of the concept of training. Prior to the provision of training services, appropriate personnel such as nurses need to comprehensively assess the individuals and plan the training accordingly.

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