Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

{"title":"[Construction of HEK293T cell line stably expressing TRPM2 channel based on PiggyBac transposition system and its application in drug screening for cerebral ischemia and other diseases].","authors":"Kaiyue Ying, Ning Hua, Yanping Luo, Xingyu Liu, Min Liu, Wei Yang","doi":"10.3724/zdxbyxb-2024-0257","DOIUrl":"10.3724/zdxbyxb-2024-0257","url":null,"abstract":"<p><strong>Objectives: </strong>To establish a cell line stably expressing the transient receptor potential melastatin 2 (TRPM2) channel for screening TRPM2 inhibitors based on PiggyBac transposition system.</p><p><strong>Methods: </strong>A plasmid PiggyBac-human TRPM2 (pPB-hTRPM2) eukaryotic expression vector was constructed using PiggyBac transposition system. The plasmid and a helper plasmid were co-transfected into HEK293T cells to express TRPM2, which was identified by fluorescence and patch-clamp assays. The high throughput screening performance was assessed with the <i>Z</i> ´ factor. Calcium imaging and patch clamp techniques were employed to assess the initial activity of eleven compound molecules, confirming the inhibitory effects of the primary molecules on TRPM2. The protective effect of the screened compounds on damaged cells was validated using the oxygen-glucose deprivation/reperfusion (OGD/R) injury model and CCK-8 kit. The level of cellular reactive oxygen species (ROS) was detected by flow cytometry. The neuroprotective effects of the compounds were evaluated using a transient middle cerebral artery occlusion (tMCAO) mouse model.</p><p><strong>Results: </strong>The HEK293T cells transfected with pPB-hTRPM2-EGFP showed high <i>TRPM2</i> expression. Puromycin-resistant cells, selected through screening, exhibited robust fluorescence. Whole-cell patch results revealed that induced cells displayed classical TRPM2 current characteristics comparable to the control group, showing no significant differences (<i>P</i>>0.05). With a <i>Z</i> ´ factor of 0.5416 in calcium imaging, the model demonstrated suitability for high-throughput screening of TRPM2 inhibitors. Calcium imaging and electrophysiological experiments indicated that compound 6 significantly inhibited the TRPM2 channel. Further experiments showed that 1.0 μmol/L of compound 6 enhanced cell viability (<i>P</i><0.05) and reduced the level of ROS (<i>P</i><0.05) of SH-SY5Y under OGD/R injury. 0.3 and 1.0 mg/kg of compound 6 reduced the cerebral infarction volume in tMCAO mice (both <i>P</i><0.05).</p><p><strong>Conclusions: </strong>A stable TRPM2 gene expressing cell line has been successfully established using PiggyBac gene editing in this study. TRPM2 channel inhibitors were screened through calcium imaging and patch clamp techniques, and an inhibitor compound 6 was identified. This compound can alleviate cell damage after OGD/R by reducing cellular ROS levels and has a protective effect against cerebral ischemia-reperfusion injury in mice.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"604-614"},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Application of prophylactic flow restriction in brachiocephalic arteriovenous fistulas].","authors":"Jue Wang, Xuan Zheng, Yajin Zhu, Guoning Zhu, Mingxi Lu","doi":"10.3724/zdxbyxb-2024-0092","DOIUrl":"10.3724/zdxbyxb-2024-0092","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the effects of prophylactic flow restriction for brachiocephalic arteriovenous fistula on postoperative high-flow-related complications and patency rate in patients undergoing hemodialysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical data of patients with end-stage renal disease who underwent brachiocephalic arteriovenous fistula surgery for hemodialysis from February 2017 to May 2022 in Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were retrospectively analyzed. During surgery, a 4-5 mm vascular suture loop was placed around the vein near the anastomosis as a flow restriction device in 43 patients (flow restriction group), while 42 patients did not receive the prophylactic flow restriction ring (control group). All patients were followed up for 1 to 5 years. The incidence rates of complications related to the hemodialysis access pathway, including distal ischemia syndrome, the formation of arteriovenous fistula aneurysms, thrombus, high-flow congestive heart failure, anastomosis of the vein within 1 cm of the anastomosis and cephalic arch stenosis, were compared between the two groups. The natural blood flow rate of the arteriovenous fistula, anastomosis size, the internal diameter of the vein near the anastomosis, primary patency rate, assisted primary patency rate, and secondary patency rate of the arteriovenous fistula, were also evaluated and compared between the two groups. Logistic regression analysis was used to investigate the factors affecting arteriovenous fistula patency rates, as well as the impact of the flow-restricting ring on postoperative factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Ultrasound measurements showed that the internal diameter of the vein at the site of the flow restriction ring in the flow restriction group was (3.7±0.6) mm at three months postoperatively, which was significantly smaller than the internal diameter of the narrowest part of the vein near the anastomosis in the control group [(4.1±1.0) mm, &lt;i&gt;t&lt;/i&gt;=－2.416, &lt;i&gt;P&lt;/i&gt;&lt;0.01]. The postoperative anastomotic diameter and natural blood flow rate of the arteriovenous fistula in the flow restriction group were both significantly lower than those in the control group (both &lt;i&gt;P&lt;/i&gt;&lt;0.05). Furthermore, the incidence rates of various complications in the flow restriction group were significantly lower than those in the control group (all &lt;i&gt;P&lt;/i&gt;&lt;0.05). At 6, 12, and 24 months postoperatively, the primary patency rate and assisted primary patency rate in the flow restriction group were significantly higher than those in the control group (both &lt;i&gt;P&lt;/i&gt;&lt;0.05), while there was no significant difference in secondary patency rates between the two groups (&lt;i&gt;P&lt;/i&gt;&gt;0.05). Binary logistic regression analysis indicated that age, diabetes, and natural blood flow rate of the arteriovenous fistula at 3 months postoperatively were independent risk factors for primary patency rate, while the ","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"623-631"},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mature oocyte found during ovarian tissue cryopreservation in an early adolescent female.","authors":"Haocheng Zhang, Libing Shi, Haichao Wang, Haiyan Zhu","doi":"10.3724/zdxbyxb-2023-0561","DOIUrl":"10.3724/zdxbyxb-2023-0561","url":null,"abstract":"<p><p>A 15-year-old female with Hodgkin's lymphoma underwent ovarian tissue cryopreservation for preserving fertility in Reproductive Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medical after receiving one course of chemotherapy. During the ovarian tissue cryopreservation, one MⅡmature oocyte and three germinal vesicle oocytes were found. The three immature oocytes underwent <i>in vitro</i> maturation but failed. Ultimately, one mature oocyte and 12 ovarian cortex slices were cryopreserved using vitrification. This case indicates that for patients with established gonadal axis feedback, ovarian tissue cryopreservation may not be the only method for fertility preservation. It is advisable to consider ovarian stimulation and oocyte retrieval for oocyte cryopreservation. Alternatively, for individuals in the ovulation phase of their menstrual cycle, attempting oocyte retrieval before ovarian tissue cryopreservation to obtain mature oocytes from the natural cycle, followed by oocyte cryopreservation, may enhance the likelihood of successful fertility preservation.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"53 4","pages":"527-530"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic value of ultrasonography for injury of anterior talofibular ligament and anterior inferior tibiofibular ligament distal fascicle in patients with ankle fractures.","authors":"Panpan Lyu, Chao Liu, Shiyan Li","doi":"10.3724/zdxbyxb-2023-0602","DOIUrl":"10.3724/zdxbyxb-2023-0602","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the diagnostic value of ultrasonography for injuries of anterior talofibular ligament (ATFL) and anterior inferior tibiofibular ligament distal fascicle (ATiFL-DF) in patients with ankle fractures.</p><p><strong>Methods: </strong>Clinical data of 51 patients with ankle fractures who were clinically suspected of ligament injuries and underwent ankle ultrasonography examination and arthroscopy in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from April 2019 to March 2023 were retrospectively analyzed. Using arthroscopic results as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ultrasonography in diagnosing ATFL and ATiFL-DF injuries were evaluated, and Kappa consistency test was performed.</p><p><strong>Results: </strong>The sensitivity and specificity of ultrasonography in diagnosis of ATFL injury were 100.0% and 92.3%, with the PPV of 92.6% and NPV of 100.0%. Ultrasonography findings exhibited excellent concordance with arthroscopic results (<i>kappa</i>=0.849). The sensitivity and specificity of ultrasonography in diagnosis of ATiFL-DF injury was 86.7% and 33.3%, with the PPV of 90.7% and NPV of 25.0%. However, the consistency between ultrasonography and arthroscopic results was poor (<i>kappa</i>=0.168).</p><p><strong>Conclusions: </strong>Ultrasonography is reliable in assessing injuries of ATFL in patients with ankle fractures, but its specificity in diagnosing ATiFL-DF is poor. Therefore, ankle arthroscopy remains necessary for ankle fracture patients with negative findings of ATiFL-DF in ultrasonography.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"411-418"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomical and biomechanical characteristics of basivertebral foramen and its clinical significance.","authors":"Shengyun Li, Xing Zhao","doi":"10.3724/zdxbyxb-2024-0220","DOIUrl":"10.3724/zdxbyxb-2024-0220","url":null,"abstract":"<p><p>Basivertebral foramen is a natural orifice in the posterior wall of the vertebral body existing in humans and mammals, through which the basal vertebral vein, branch of lumbar artery and recurrent branch of spinal nerve enter and exit the vertebral body. Basivertebral foramen changes the local microstructure of the vertebral body, resulting in cortical defect and sparse trabecular bone in the central region of the vertebral body, thus affecting its biomechanical characteristics and making its central region a \"weak\" area of the vertebra. Some characteristic injuries of the vertebra are related to basivertebral foramen, such as vertebral compression fracture and intervertebral cleft, vertebral burst fracture and posterior upper vertebral fracture fragment, and cement leakage during treatment. In this article, the anatomical and developmental biological characteristics of basivertebral foramen, the impact of basivertebral foramen on biomechanical characteristics, and the treatment of basivertebral foramen related vertebral diseases are reviewed, in order to provide references for the clinical diagnosis and treatment of vertebral injuries.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"53 4","pages":"443-449"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinusoidal alternating electromagnetic field accelerates fracture healing in rats.","authors":"Yuhai Gao, Xuefeng Hou, Zhenlong Wei, Keming Chen","doi":"10.3724/zdxbyxb-2023-0454","DOIUrl":"10.3724/zdxbyxb-2023-0454","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of sinusoidal alternating electromagnetic field (SEMF) on fracture healing and its mechanism.</p><p><strong>Methods: </strong>Femoral fracture model was established using specific pathogen free male Wistar rats. Thirty rats were randomly divided into the control and SEMF groups with 15 rats in each group. The SEMF group was given 50 Hz 1.8 mT for 90 min every day, while the control group was not treated. X-ray examinations were performed every two weeks to determine the formation of bone scabs. Three rats from both groups were sacrificed after 2 and 4 weeks of treatment. Protein was extracted from the fractured femurs, and the expression of type Ⅰ collagen (COL-1), osterix (OSX), Runt-related transcription factor 2 (RUNX2), and vascular endothelial growth factor (VEGF) was detected by Western blotting. After 8 weeks, the femur on the operated side was taken for micro-CT scanning to observe fracture healing, angiography to observe blood vessel growth, and organs such as hearts, livers, spleens, lungs, and kidneys were taken for safety evaluation by hematoxylin-eosin staining (HE staining).</p><p><strong>Results: </strong>The bone scab scores of the SEMF group were significantly higher than those of the control group after 2, 4, 6, and 8 weeks of treatment (all <i>P</i><0.01). The fracture healing of the SEMF group was better than that of the control group after 8 weeks, and the bone volume scores of the two groups were 0.243±0.012 and 0.186±0.008, respectively (<i>P<</i>0.01); the number of blood vessels in the SEMF group was also more than that of the control group after 8 weeks. Western blotting results showed that the expressions of COL-1, OSX, RUNX2, and VEGF were higher in the SEMF group than those in the control group after 2 and 4 weeks of treatment (all <i>P</i><0.05). HE staining showed that histopathological results of the examined organs were normal in both groups.</p><p><strong>Conclusions: </strong>SEMF can accelerate fracture healing by promoting the expression of osteogenic factors and vascular proliferation without significant adverse effects.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"419-426"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of signal recognition particle 14 in hepatocellular carcinoma and its relationship with disease progression and patient survival.","authors":"Huimin Tian, Dongmei Tang, Meilin Ma, Xianghui Fu","doi":"10.3724/zdxbyxb-2024-0055","DOIUrl":"10.3724/zdxbyxb-2024-0055","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the expression of signal recognition particle 14 (SRP14) in hepatocellular carcinoma (HCC) and its clinical significance.</p><p><strong>Methods: </strong>The data of SRP14 expression in HCC were obtained from bioinformatics study, and from investigation with quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemical staining and Western blotting in clinical samples. The Kaplan-Meier analysis was used to determine the associations between <i>SRP14</i> mRNA expression and the overall survival, progression-free survival, and disease-specific survival of HCC patients. The effect of SRP14 on the proliferation and migration of HCC cells were determined by EdU staining, MTS, Transwell and wound-healing assays. The potential mechanism for SRP14 regulating HCC was explored through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis as well as qRT-PCR.</p><p><strong>Results: </strong>According to the data from GSE14520, TNMplot database and clinical samples, compared with paired tumor-adjacent tissues, non-paired tumor-adjacent tissues and normal tissues, the mRNA expression of <i>SPR14</i> in HCC tissues was upregulated (all <i>P</i><0.05). In clinical samples, compared with paired tumor-adjacent tissues, the protein expression of SPR14 in HCC tissues was increased (<i>P</i><0.05). The increased mRNA expression of <i>SRP14</i> was associated with good overall survival, progression-free survival, and disease-specific survival in HCC patients. SRP14 inhibited the proliferation and migration of HCC cells <i>in vitro</i>. According to the KEGG and GO enrichment analysis, in non-specific HCC, the genes co-expressed with SRP14 may predominantly regulate protein synthesis, processing, and transport, while in nonalcoholic fatty liver disease related HCC, the genes co-expressed with SRP14 could control multiple signaling pathways such as MAPK, cAMP, PI3K-Akt, and Wnt. Mechanistically, SRP14 up-regulated the mRNA expression of tumor suppressor gene <i>GPRC5A</i> inHCC cells (<i>P</i><0.05).</p><p><strong>Conclusions: </strong>SRP14 may regulate HCC progression and influence patient prognosis.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"53 4","pages":"460-471"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical study on anterolateral femoral interregional flap with turbocharge technique in the repair of large limb wounds.","authors":"Haifeng Zhu, Xiaodong Yang, Haitao Wang, Lifeng Shen","doi":"10.3724/zdxbyxb-2023-0613","DOIUrl":"10.3724/zdxbyxb-2023-0613","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of large limb wounds.</p><p><strong>Methods: </strong>Clinical data of 38 patients with large limb surface wound (11 cm×39 cm-16 cm×65 cm) admitted to the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from May 2018 to May 2022 were retrospectively analyzed. Eighteen patients were treated by anterolateral thigh perforator flap combined with superficial circumflex iliac artery flap (ALTP-SCIAP) with turbocharge technique (interregional flap group); while 20 patients were treated with unilateral or bilateral anterolateral femoral flaps, combined with skin grafting if necessary (traditional anterolateral femoral flap group). The survival of skin flap, repair of donor area, complications and patient satisfaction were compared between the two groups.</p><p><strong>Results: </strong>In interregional flap group, 18 flaps were harvested and transplanted, the flap width, length and the viable area were (9.9±2.0) cm, (44.2±3.5) cm and (343.2±79.9) cm², respectively. In traditional anterolateral femoral flap group, 29 flaps were harvested and transplanted, the flap width, length and the viable area were (11.0±2.8) cm, (21.7±3.2) cm and (186.4±49.2) cm², respectively. There were significant differences in the flap length and the viable area between the two groups (<i>t</i>=22.365 and 8.345, both <i>P</i><0.05). In the interregional flap group, the donor site of flap was closed by direct suture in 11 flaps, by skin retractor assisted suture in 6 flaps, and by skin grafting in one flap. In traditional anterolateral femoral flap group, the donor site of flap was closed by direct suture in 12 flaps, by skin retractor assisted suture in 11 flaps, and by skin grafting in 6 flaps. The skin graft rates of the two groups were 5.6% (1/18) and 20.7% (6/29), respectively (<i>χ</i>²=2.007, <i>P</i>>0.05). The interregional flap group had lower postoperative complications rate (5.6% <i>vs.</i> 35.0%, <i>χ</i>²=4.942, <i>P</i><0.05) and higher patient satisfaction rate (94.4% <i>vs.</i> 70.0%, <i>χ</i>²=4.448, <i>P</i><0.05) than traditional anterolateral femoral flap group.</p><p><strong>Conclusions: </strong>Compared with the traditional anterolateral femoral flap, the anterolateral femoral interregional flap with turbocharge technique has a larger flap area, most of the donor areas of the flap can be sutured directly without skin grafting and with less complications and a higher patient satisfaction rate.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"401-410"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of R-loop binding proteins with prognosis and anti-tumor drug sensitivity in lung adenocarcinoma: a bioinfor-matic study.","authors":"Tingye Wang, Yanlin Ding, Li Tao","doi":"10.3724/zdxbyxb-2024-0032","DOIUrl":"10.3724/zdxbyxb-2024-0032","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association of R-loop binding proteins with prognosis and chemotherapy efficacy in lung adenocarcinoma.</p><p><strong>Methods: </strong>The data related to R-loop regulatory genes were obtained from literature of R-loop proteomics and relevant databases. We used 403 cases of lung adenocarcinoma in the Cancer Genome Atlas as training set, and two datasets GSE14814 and GSE31210 in Gene Expression Omnibus as validation sets. The weighted gene co-expression network analysis (WGCNA) was employed to identify R-loop genes with a significant impact on the clinical phenotype of lung adenocarcinoma. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to eliminate genes exhibiting multicollinearity. A multivariate Cox regression analysis was employed to scrutinize clinical variables and R-loop characteristic genes that exert independent prognostic effects on patient survival. Subsequently, a risk score model was constructed. The predictive capacity of this model for the prognosis of patients was analyzed and validated. Additionally, the performance of risk model on the anti-tumor drug sensitivity was assessed. The mutations of R-loop genes were analyzed by maftools. The effect of PLEC expression on anti-tumor drug sensitivity was tested on non-small cell lung adenocarcinoma H1299 and A549 cells <i>in vitro</i>.</p><p><strong>Results: </strong>A collection of 1551 R-loop genes were obtained, and 78 genes exhibited significant effects on the clinical phenotype shown on WGCNA. The LASSO regression analysis retained fourteen R-loop genes. A multivariate Cox regression analysis further identified three R-loop genes (<i>HEXIM1</i>, <i>GLI2</i>, <i>PLEC</i>) and a clinical variable (tumor grading) that were associated with patient prognosis. Risk prediction model was established according to the regression coefficients of each parameter. Kaplan-Meier survival analysis showed that the prognosis of high-risk group was significantly worse than that of low-risk group (<i>P</i><0.01). The time-dependent ROC curve showed that the risk model had good predictive ability in both training and validation sets. Predictive analyses of anti-neoplastic drug sensitivity indicated a diminished responsiveness to both chemotherapy and targeted treatment drugs among high-risk patients. The expression of PLEC was strongly correlated with sensitivity to gefitinib, a classical EGFR inhibitor.</p><p><strong>Conclusions: </strong>R-loop binding proteins have been identified as significant determinants in the prognosis and therapeutic strategies for lung adenocarcinoma, which indicates that therapeutic interventions targeting these specific R-loop binding proteins might contribute to a better survival of the patients.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"472-480"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decarbromodiphenyl ether exposure promotes migration of triple-negative breast cancer cells through miR-221 in extracellular vesicles.","authors":"Mengxiao Jiang, Lizhen Wang, Linming Lu, Youhua Tong, Yanyu Li, Hui Zhi","doi":"10.3724/zdxbyxb-2024-0063","DOIUrl":"10.3724/zdxbyxb-2024-0063","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of decarbromodiphenyl ether (BDE-209) exposure on the migration ability of triple-negative breast cancer (TNBC) cells and to explore the underlying mechanism.</p><p><strong>Methods: </strong>Human TNBC MDA-MB-231 cells were divided into blank control group and BDE-209 exposure groups (treated with 0.02, 0.20, 2.00, 20.00 and 200.00 ng/mL BDE-209 in high glucose DMEM). Extracellular vehicles (EVs) secreted by MDA-MB-231 cells were isolated by differential ultracentrifugation. Transmission electron microscopy (SEM), nanoparticle tracking analysis (NTA) and Western blotting were performed to characterize the EVs. The effect of the EVs induced by BDE-209 exposure (EVs-BDE-209) on the migration and invasion of MDA-MB-231 cells was detected by wound-healing assay and Transwell test. qRT-PCR was used to measure the miR-221 level in EVs-BDE-209. The expression of MMP9 in MDA-MB-231 cells was determined by Western blotting.</p><p><strong>Results: </strong>Compared with the blank control, BDE-209 exposure increased the tumor cell-derived EVs in dose-dependent manner. The MDA-MB-231 cells co-cultured with EVs released by 200.00 ng/mL BDE-209 exposure showed an 86% increase in cell migration rate, a 1.32-fold higher number of membrane-penetrating cells, a 2.71-fold higher expression level of miR-221, and a 1.62-fold higher expression level of MMP9 compared with the blank control group (all <i>P</i><0.05). While transfection with anti-miR-221 antibody to decrease miR-221 level in EVs significantly reversed the increased invasion ability of the MDA-MB-231 cells treated with EVs-BDE-209.</p><p><strong>Conclusions: </strong>BDE-209 exposure may promote metastasis potential of MDA-MB-231 cells via EVs-BDE-209 transmitted miR-221.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"53 4","pages":"481-489"},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}