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Mesenchymal stromal cells (MSCs) have therapeutic potential due to their abilities of differentiation, immunomodulation, and migration to injured tissues, potentiating such effects when cells are activated. Guarana (Paullinia cupana) is a tropical plant species found in South America that is known for its antioxidant, stimulant, and cicatricial effects. The guarana extract is composed of many substances and caffeine is the main component. The objective was to evaluate the effects of guarana and caffeine on MSCs. After the initial characterization, MSCs were treated with Paullinia cupana (10, 100, and 1000 μg/mL) or caffeine (0.4, 4, and 40 μg/mL) for 24 h. MSCs treatment with 1000 μg/mL guarana increased cell polarity, viability, cell migration to chemoattractant, antioxidant potential, and liberation of extracellular vesicles (EVs), while it reduced the levels of autophagy. MSCs treated with 100 and 1000 μg/mL guarana or 40 μg/mL caffeine showed a decrease of cell proliferation. No treatment affected the cellular area and cell cycle of MSCs. The study shows in vitro evidence that guarana could be a promising alternative for activating MSCs to promote better cellular products for future clinical therapies.
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@#OBJECTIVE To provide reference for guiding the individualized drug therapy management of imatinib for gastrointestinal stromal tumor （GIST）， with the goal of enhancing patient survival rates and improving their quality of life. METHODS Using a nominal group technique， a multidisciplinary （clinical， pharmaceutical and evidence-based） expert panel was formed to create the Consensus of Chinese Experts on Individualized Medication Management of Imatinib for Gastrointestinal Stromal Tumors outline through joint discussions. The expert panel conducted systematic retrieval， analysis， and summarization of the outline’s content， and reached relevant consensus based on China’s current situation， clinical needs， and research evidence. An external expert panel was also formed， comprising experienced multidisciplinary experts in clinical practice. Delphi method questionnaire was employed to openly collect the external experts’ opinions， which were then organized， summarized， analyzed， provided with feedback， revised， and finally formed into a consensus. RESULTS & CONCLUSIONS The drafting of this consensus included the clinical application of imatinib in neoadjuvant therapy for GIST patients， adjuvant therapy for adult patients with significant risk of recurrence after surgical resection， and drug therapy for patients with recurrent， metastatic， or unresectable tumors； pharmaceutical monitoring and long-term medication management. This consensus provides standardized processes and methods for medical institutions in individualized drug therapy management for GIST patients and holds significant importance in improving the clinical efficacy of imatinib and ensuring drug safety.
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Gastrointestinal stromal tumor(GIST),with a certain malignant potential,are currently the most common subepithelial tumors of the gastrointestinal tract.Early diagnosis and prediction of malignant potential are very important for the formulation of a treatment plan and determining the prognosis of GIST.Deep learning technology has made significant progress in the diagnosis of digestive tract diseases,and it can also effectively assist physicians in diagnosing GIST and predicting their malignant potential,preoperatively.The application of deep learning technology in the diagnosis of GIST includes CT,gastrointestinal endoscopy and endoscopic ultrasound.This paper aims to review the application of deep learning technology in the diagnosis and prediction of malignant potential of GIST.
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Objective:To study the effect of gauze filtration on the content of adipose stem cells in fat gel.Methods:In March 2022, fat samples from 5 patients who underwent abdominal fat aspiration at the Hunan Provincial People′s Hospital were collected, prepared fat ged, the fat gel was filtered 1-5 times with 2 layers of gauze, and the amount of fat gel passing through a 1 ml threaded syringe with a 27 G needle was measured after each filtration. At the same time, the content of fat stem cells in the filtered fat gel was detected by flow cytometry.Results:As the number of filters increases, the amount of fat gel passing through gradually increased. The increasing trend was obvious after the first to fourth filters, and the increasing trend slowed down after the fifth filter. After statistical analysis, the differences between the first filter and the second filter, the second filter and the third filter, and the third filter and the fourth filter were statistically significant ( P<0.05). There was no statistically significant difference between the fourth filter and the fifth filter ( P>0.05). As the number of filters increased, the content of adipose stem cells in the fat gel gradually decreased. The decreasing trend was obvious after the first to third filters, and the decreasing trend slowed down after the fourth filter. After statistical analysis, the differences between the first filter and the second filter, as well as the second filter and the third filter, were statistically significant (all P<0.05). However, there was no statistically significant difference between the third filter and the fourth filter, and the fourth filter and the fifth filter (all P>0.05). Conclusions:The more times gauze is filtered, the better the permeability of fat gel. However, the content of adipose stem cells will significantly decrease in the first three filters. Therefore, the number of times gauze is filtered for fat gel should be minimized as much as possible.
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Objective:To investigate the effect of astragaloside IV (AS-IV) regulating the signal axis of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) on the mobilization of bone marrow endothelial progenitor cells (EPCs) to peripheral blood in diabetes skin ulcer (DSU) rats.Methods:Twenty four SPF grade male Sprague Dawley (SD) rats were selected to make the model of type 2 diabetes rats by intraperitoneal injection of 30 mg/kg 1% (plastid ratio) streptozotocin, and then round full-thickness skin with a diameter of 2 cm was cut on both sides of the waist and back to make the skin ulcer model of diabetes rats. After that, they were randomly divided into AS-IV group (50 mg/kg AS-IV), blocker group (50 mg/kg AS-IV+ 5 mg/kg AMD3100) and model group. At the same time, a blank group ( n=8) was set up, The drug was administered via intraperitoneal injection, and the model group and blank group were treated with 0.9% NaCl of equal volume. On the 10th day, peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats were collected. The number of EPCs in peripheral blood of each group of rats was measured by flow cytometry, and the protein expression of SDF-1α and CXCR4 in peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats was detected by enzyme-linked immunosorbent assay (ELISA); At the same time, the wound healing rates of each group were tested. Results:On the 10th and 21st day after modeling, the wound healing rate of each group of rats was compared. The blank group healed the fastest, while the model group healed the slowest. The AS-IV group had better healing than the model group and the blocker group, and the difference was statistically significant (all P<0.05). On the 10th day after modeling, the positive rates of peripheral blood EPCs in the white group, AS-IV group, and blocker group were significantly higher than those in the model group (all P<0.05), while the positive rates of peripheral blood EPCs in the blocker group were significantly lower than those in the AS-IV group (all P<0.05). On the 10th day after modeling, the protein expression of SDF-1α and CXCR4 in the wound, serum, and bone marrow of the model group was the lowest, while the protein expression in the blank group was the highest (all P<0.05). The protein expression of SDF-1α and CXCR4 in the wound, serum, bone marrow of the AS-IV group was significantly higher than that of the blocker group and model group, and the difference was statistically significant (all P<0.05). Conclusions:Astragaloside IV can promote the mobilization and migration of endothelial progenitor cells from bone marrow to peripheral blood in diabetes ulcer rats by regulating SDF-1α/CXCR4 signal axis, and can participate in angiogenesis of diabetes ulcer wounds as seed cells to promote the healing of diabetes skin ulcers.
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Objective:To investigate the conversion of stromal vascular fraction (SVF) in the microenvironment of radiation-induced skin injuries to provide guidance for clinical applications.Methods:Based on a random number table, C57BL/6N mice were categorized into four groups: the blank control, negative control, acute injury, and chronic injury groups, with each group containing 25 mice. The backs of mice in the blank control, acute injury, and chronic injury groups were exposed to 15 Gy X-ray irradiation. Then, the mice in the negative control, acute injury, and chronic injury groups were injected subcutaneously with the SVF derived from B6/G-R mice. The survival of these mice was observed 1, 3, 7, 14, and 21 d after the injection through fluorescence tracing and in vivo imaging. Accordingly, the clinical SVF injection regimens were optimized based on the experimental result of mice. Finally, local SVF injection was performed on different frequencies for patients in different wound conditions, with the efficacy being observed. Results:The fluorescence of SVF was observed from the tissue slices of the acute injury, chronic injury, and negative control groups 14 d post-injection. The result showed that the fluorescence intensity of SVF 1, 3, and 7 d post-injection was in the order of the negative control group > the acute injury group > the chronic injury group. The acute injury group ranked at the top and the chronic injury group remained at the bottom 14 d after the injection. The fluorescence of SVF in each group was barely detected 21 d after the injection. Compared to the negative control group, the acute injury group exhibited statistical differences only 14 d post-injection ( t = 4.11, P < 0.05), while the chronic injury group displayed statistical differences 1, 3, 7, and 14 d after the injection ( t = 3.88-5.74, P < 0.05). Furthermore, the acute injury group exhibited significantly higher fluorescence intensity of SVF than the chronic injury group ( t = 4.73-8.38, P < 0.05). The half-life of SVF for the negative control, acute injury, and chronic injury groups was 6.336, 6.014, and 2.163 d, respectively. As indicated by the application of SVF transplantation based on traditional surgical protocols in the clinical trial, SVF can significantly promote wound repair, with earlier SVF transplantation being more beneficial for wound healing. Conclusions:The conversion of SVF differs in the microenvironments of acute and chronic radiation-induced skin injuries. This can serve as an essential guide for the administration timing and injection frequency of SVF in clinical applications.
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Objective:To analyze the expression and prognosis of B-cell lymphoma 7 protein family member A (BCL7A) in hepatocellular carcinoma, as well as the effect and mechanism of BCL7A expression on the invasion and migration of hepatocellular carcinoma cells.Methods:The cancer tissues and adjacent tissues of 40 patients with hepatocellular carcinoma who underwent radical hepatobiliary resection in the Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University from November 2017 to March 2018 were prospectively collected for protein extraction, including 29 males and 11 females, aged (58.5±10.4) years. The information of 374 cases of hepatocellular carcinoma and 50 cases of adjacent tissues were downloaded from The Cancer Genome Atlas (TCGA) database, and the hepatocellular carcinoma cell lines Hep3B and SMMC-7721 were transfected with overexpressing BCL7A plasmid and empty vector plasmid (negative control), respectively. Western blotting and immunohistochemistry were used to detect the expression of BCL7A, and Western blotting was also used to detect the expression of proteins related to epithelial-mesenchymal transition (N-cadherin, E-cadherin, snail). Transwell and cell scratch assays were used to detect cell invasion and migration.Results:Compared with adjacent tissues, the mRNA expression of BCL7A in 50 patients with hepatocellular carcinoma in TCGA was significantly increased ( t=13.38, P<0.001). According to the median mRNA expression level of BCL7A, 374 patients were divided into BCL7A high expression group ( n=187) and low expression group ( n=187), and the cumulative survival rate of BCL7A high expression patients was lower than that of low expression group, and the difference was statistically significant ( χ2=6.95, P=0.009). Western blot was used to detect the relative expression of BCL7A protein in cancer tissues, and found it was higher compared to adjacent tissues. Compared with the negative control group, the number of cells invaded by the BCL7A overexpression group of hepatoma cells Hep3B and SMMC-7721 was more than the negative control group respectively, (153.7±1.3) vs (63.7±4.7) and (307.7±25.14) vs (72.3±12.5), and the differences were statistically significant ( t=7.97, 8.38, both P=0.001) .The results of the cell scratch assay were consistent with the results of the Transwell invasion assay. The expressions of N-cadherin and snail in the BCL7A overexpression group were higher than those in the negative control group, and the E-cadherin was lower, and the difference was statistically significant (all P<0.05). Conclusions:The expression of BCL7A in cancer tissues of patients with hepatocellular carcinoma is elevated and is associated with poor prognosis. BCL7A may promote hepatocellular carcinoma cell metastasis and invasion by promoting epithelial-mesenchymal transition.
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This paper reported the clinical characteristics, diagnosis, and treatment of a case of recurrent endometrial stromal sarcoma with term pregnancy. The patient had undergone laparoscopic surgery to remove hysteromyoma before conception in 2017, which was pathologically diagnosed as low-grade endometrial stromal sarcoma after surgery. Due to her strong reproductive willingness, the patient attempted to conceive in light of her stable condition and no evidence of recurrence and was closely followed up with an informed choice. She conceived successfully in 2020 and underwent regular pregnancy examinations. Ultrasound examination at 37 +4 weeks of gestation revealed a slightly hypoechoic mass of about 6.3 cm×4.5 cm size in the pelvic cavity. After admission, a pelvic MRI indicated multiple solid nodules in the right adnexa uteri and beside the iliac vessels in the left pelvic wall and anterior pelvic wall with the larger one being about 58 mm×28 mm. Diffusion-weighted imaging showed multiple pelvic nodules and masses with significant diffusion restriction. The patient was diagnosed as having multiple solid nodules and masses in the pelvic cavity, and the recurrence of sarcoma was highly suspected. Brain CT and lung CT showed no obvious metastatic lesions. A consultation involving the Department of Gynecological Tumor Chemoradiotherapy was held and the sarcoma recurrence during pregnancy was prenatally diagnosed. After ruling out the contraindications for surgery, a cesarean section was performed in the lower segment of uterus under general anesthesia and a live female baby was delivered at 38 ＋3 weeks. The excised mass was confirmed as recurrent uterine stromal sarcoma by rapid freezing pathology during cesarean section. A combination surgery was performed subsequently, including total extra-fascial hysterectomy, bilateral oophorectomy, bilateral salpingectomy, appendectomy, greater omentum resection, pelvic lesion resection (right side), and pelvic adhesiolysis. Recurrent low-grade uterine stromal sarcoma was reconfirmed by postoperative pathology. The patient was discharged after recovery. After two years of follow-up, no distant metastasis recurrences were found.
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Objective To screen the active components of total flavonoid extracts of Sarcandra glabra to promote megakaryocyte differentiation.Methods(1)A model of megakaryocyte differentiation disorder was established by co-culturing human megakaryocytic leukaemia cells(Dami)with human bone marrow stromal cells(HS-5)as an evaluation system,and the experimental groupings were as follows:the Dami group(Dami),the control group(Dami+HS-5),and the PMA group[Dami+HS-5+5 ng·mL-1 foprolol 12-tetradecanoate 13-acetate(PMA)],and model group[Dami+HS-5+1%rabbit anti-rat platelet serum(APS)+5 ng·mL-1 PMA]were cultured for 48 hours.The expressions of megakaryocyte differentiation and maturation surface marker molecules,CD41a and CD61 were detected by flow cytometry.(2)Forty-nine SD male rats were randomly divided into blank plasma group,15-minute group,30-minute group,60-minute group,90-minute group,120-minute group,and 240-minute group,with 7 rats in each group.The rats in each administration group were gavaged with 1.26 g·kg-1 of total flavonoids extracts of Sarcandra glabra,and blood was collected at six set time points(15,30,60,90,120,240 minutes)for the preparation of time-dependent serum-containing plasma of total flavonoids extracts of Sarcandra glabra.(3)Ultra-high performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UHPLC-Q-TOF/MS)was used to analyze the plasma of the time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra,and the peak area was used to construct a matrix(X-matrix)of the amount of chemical composition change over time in the time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra.The collected time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra at six different time points was used to intervene in the model of megakaryocyte differentiation and maturation disorder,and the expression of cell surface molecules CD41a and CD61 was detected by flow cytometry to construct the matrix of effect of time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra(Y-matrix).(4)After the data of X and Y matrices were standardized,partial least squares(PLS)was used to calculate and analyze the quantitative and qualitative effect relationship,and variable importance for projection(VIP)>1 was used as the threshold to screen the effect components related to the changes of cell surface molecules CD41a and CD61,and chemical composition identification,as the potential effector components in the total flavonoid extracts of Sarcandra glabra were used to promote the differentiation of megakaryocytes,and finally the regression evaluation system was used to verify the efficacy of its medicinal effect.Results(1)Compared with the Dami group,the expression level of CD41a on the surface of Dami cells in the control group was significantly increased(P＜0.05).Compared with the control group,the expression levels of CD41a and CD61 on the surface of Dami cells in the PMA group were significantly increased(P＜0.01).Compared with the PMA group,the expression levels of CD41a and CD61 on the surface of Dami cells in the model group were significantly reduced(P＜0.01).(2)Compared with the blank plasma group,the expression levels of the molecules CD41a and CD61 on the surface of Dami cells at each time point of 15,30,60,90,120,and 240 minutes were significantly increased(P＜0.01),and the expression levels of CD41a and CD61 were both highest in the 30-minute group.The potential effective components with VIP value greater than 1 were screened out in the positive and negative ion mode,and 540.3638@12.25 and 559.2991@11.53 were selected for pharmacodynamic verification.559.2991@11.53 was identified as daucosterol(Dau),540.3638@12.25 was identified as rosmarinic acid 4-O-β-D-glucoside(Ros).After Ros and Dau intervened in the megakaryocyte differentiation and maturation disorder model respectively,the expression levels of CD41a and CD61 on the surface of Dami cells in the low-,medium-and high-dose groups(40,60 and 80 μg·mL-1)of Ros and Dau were significantly increased compared with the model group(P＜0.05,P＜0.01).Conclusion Ros and Dau may be the active components of the total flavonoids extracts of Sarcandra glabra to promote the differentiation of megakaryocytes.
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Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.
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Objective To explore the influence and mechanism of lentiviral vector-mediated steroidogenic factor-1(SF-1)silence on decidual process of human endometrial stromal cells(hESCs).Methods The endometrial tissues of patients with endometriosis(EM)and normal pregnant women were collected,and the differential expression of SF-1 was detected by Real-time PCR and immunohistochemical staining.hESCs were isolated from the endometrial tissue of normal pregnancy and identified,hESCs were divided into control group,estradiol(E2)+progesterone(P4)group,short hairpin RAN(shRNA,sh)-normal control(NC)+E2+P4 group,sh-SF-1+E2+P4 group,after the corresponding processing,the morphological changes of hESCs were observed under an inverted microscope.Real-time PCR and Western blotting were used to detect the mRNA expression levels and protein levels of human insulin-like growth factor-binding protein-1(IGFBP-1)and prolactin(PRL)in cells,respectively,flow cytometry was used to determine the cycle distribution of the cells,immunofluorescence staining was used to observe the expression of the intracellular auto-bid microtubule-associated protein light chain 3(LC3),Western blotting was used to determine the protein level of intracellular autophagy-related proteins LC3-Ⅱ,LC3-Ⅰ and Beclin-1.Results The relative expression of SF-1 mRNA and the positive rate of SF-1 protein in endometrial tissue of EM patients were higher than those of normal pregnancy endometrial tissue(P<0.05).Compared with the sh-NC+E2+P4 group,the cells in the sh-SF-1+E2+P4 group were mostly long-spindle,and there was no obvious decidualization.The relative mRNA expression and protein expression of IGFBP1 and PRL were significantly down-regulated(P<0.05),the proportion of cells in G0/G1 phase was significantly decreased,the proportion of cells in S phase was significantly increased(P<0.05),the ratio of LC3-Ⅱ/LC3-Ⅰwas significantly increased,and the relative expression of Beclin-1 protein was also significantly up-regulated(P<0.05).Conclusion The expression of SF-1 in the endometrial tissue of EM patients is increased,and SF-1 silencing mediated by lentiviral vector can inhibit the decidualization process of hESCs,which may be related to regulating the level of autophagy.
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Objective·To investigate the effect of neferine(Nef)on renal tissues of diabetic nephropathy(DN)rats and its related mechanism.Methods·DN model rats were constructed by feeding high-fat diet combined with intraperitoneal injection of streptozotocin,and the successfully constructed rats were randomly divided into DN group,Nef(low,medium and high)dose groups and Nef high-dose+pathway antagonist(AMD3100)group,with 10 rats in each group.At the same time,10 common rats were selected as the normal group.The levels of fasting blood glucose(FBG),24 h urinary protein,serum glycosylated hemoglobin(HbA1c),serum creatinine(Scr),blood urea nitrogen(BUN)and renal index of rats in the six groups were measured.Hematoxylin-eosin(H-E)and Masson staining were used to observe the pathological changes of renal tissues.The content of malondialdehyde(MDA)in renal tissues was determined by thiobarbituric acid(TBA)method,and the activities of superoxide dismutase(SOD)and catalase(CAT)in renal tissues were determined by water soluble tetrazolium(WST-1)method and ammonium molybdate method,respectively.The mRNA and protein expressions of stromal cell-derived factor-1(SDF-1)and CXC chemokine receptor 4(CXCR4)in renal tissues were detected by quantitative real-time PCR(qPCR)and Western blotting,respectively.Rat renal tubular epithelium cells NRK-52E were induced by high glucose(30 mmol/L glucose)to establish DN cell model.The cells were divided into control group,high glucose(HG)group,HG+Nef(low,medium and high)dose(i.e.HG+Nef-L,M and H)group,and HG+Nef-H +AMD3100 group.SOD and CAT activities were detected by WST-1 method and ammonium molybdate method,respectively.MDA content was detected by TBA method.The mRNA and protein expressions of SDF-1 and CXCR4 were detected by qPCR and Western blotting,respectively.CCK-8 method and flow cytometry were used to detect cell viability and apoptosis rate,respecti-vely.Results·Compared with the DN group,the levels of FBG,24 h urinary protein,HbA1c,Scr,BUN,renal index and MDA content in Nef(low,medium and high)dose groups and Nef high-dose+AMD3100 group were decreased,the mRNA and protein expressions of SDF-1 and CXCR4 were increased,and the activities of SOD and CAT were increased(all P<0.05).The degree of pathological damage and fibrosis of renal tissues was reduced;all of the above changes were dose-dependent.AMD3100 could weaken the renal protective effect of high-dose Nef on DN rats.Compared with the HG group,NRK-52E cell viability,SOD and CAT activities,and the mRNA and protein expressions of SDF-1 and CXCR4 were increased in HG+Nef-L,M and H groups,while apoptosis rate and MDA content were decreased(all P<0.05).AMD3100 could reverse the protective effect of Nef-H on NRK-52E cell damage.Conclusion·Nef may control blood glucose levels on DN rats and improve antioxidant capacity by activating the SDF-1/CXCR4 signal pathway,playing a renal protective role.
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The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.
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Objective To investigate the value of multiparametric CT features for predicting the risk classification of gastric stro-mal tumor(GST).Methods The clinical data from 139 patients with GST were retrospectively collected.According to the patho-logical risk results,the patients were divided into two groups:a low-risk GST group(including very low-and low-risk)with 75 patients and a high-risk GST group(including medium and high-risk)with 64 patients.The CT features between low-risk GST group and high-risk GST group were compared using chi-squared test or t-test.The risk factors of high-risk GST were identified by univariate analysis.The prediction models were built by multivariate logistic regression.The performance of models were evaluated by receiver oper-ating characteristic(ROC)curve.Results There were significant differences in the maximum tumor diameter,minimum tumor diameter,arterial phase enhancement degree,venous phase enhancement rate,arterial phase enhancement degree rate,venous phase enhance-ment degree rate,cystic,and necrosis between low-risk GST group and high-risk GST group,which were associated with the risk classification of GST.The area under the curve(AUC)of the quantitative features-based model that combined maximum tumor diam-eter,minimum tumor diameter,arterial phase enhancement degree,venous phase enhancement rate,arterial phase enhancement degree rate and venous phase enhancement degree rate,showed a significantly higher performance than the qualitative features-based model that incorporated cystic and necrosis(0.981 vs 0.850,P<0.001).Conclusion Maximum tumor diameter,minimum tumor diameter,arterial phase enhancement degree,venous phase enhancement rate,arterial phase enhancement degree rate,venous phase enhance-ment degree rate,as well as cystic and necrosis,are associated with the risk classification of GST and can predict the high-risk GST.
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@#Objective To investigate the diagnostic value and risk of gastrointestinal stromal tumors(GIST)by multislice spiral computed tomography(MSCT).Methods A total of 118 suspected GIST patients admitted to Huzhou Central Hospital from June 2021 to November 2022 were selected for MSCT examination and pathological examination.Taking pathological diagnosis as the gold standard,the efficacy of MSCT in diagnosing GIST was analyzed.Multifactor analysis was used to investigate the factors affecting the risk of GIST.Results Pathological diagnosis of GIST was confirmed in 103 of 118 suspected patients.The sensitivity,specificity and accuracy of MSCT diagnosis of GIST were 97.09%,86.67%and 95.76%,respectively.There were significant differences in maximum tumor diameter,tumor shape,tumor boundary,tumor density,cystic necrosis and fat space between high-risk group and low-risk group(P<0.05).The results of multifactor analysis showed that maximum tumor diameter,tumor shape,tumor density and fat space were all factors affecting the risk of GIST(P<0.05).Conclusion MSCT has a high accuracy in the diagnosis of GIST.The maximum tumor diameter,tumor shape,tumor density and fat space are all factors affecting the risk of GIST.
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Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells (MSC). However, it remains unclear what drives the compromised potency of obese MSC. In this study, we examined the involvement of adiponectin, an adipose tissue-derived hormone, in obesity-induced impaired therapeutic function of MSC. Diet-induced obesity leads to a decrease in serum adiponectin, accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC (ADSC). Interestingly, priming with globular adiponectin (gAcrp) improved the immunomodulatory potential of obese ADSC. Similar effects were also observed in lean ADSC. In addition, gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis. Mechanistically, while obesity inhibited the glycolytic capacity of MSC, gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1α axis. These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.
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AIM: To evaluate the clinical efficacy of corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking(SC-A-TE-CXL)in the treatment of severe keratoconus.METHODS: Prospective before-after self-control study. A total of 10 cases(14 eyes)of severe keratoconus with the thinnest corneal thickness(including epithelium)less than 400 μm were collected from March 2019 to July 2022 at the ophthalmology department of Affiliated Eye Hospital of Nanjing Medical University. Among them, 8 males(12 eyes)and 2 females(2 eyes)were treated with SC-A-TE-CXL. Corneal curvature, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), the thinnest corneal thickness(TCT), central corneal thickness(CCT), non-contact intraocular pressure, endothelial cell density(ECD)and anterior or posterior elevations at the thinnest point before surgery and at 1, 3, 6 and 12 mo postoperatively were observed and recorded, as well as corneal cross-linking depth at 1 mo postoperatively.RESULTS: UCVA and BCVA at 1, 3, 6, and 12 mo after SC-A-TE-CXL were higher than those preoperatively, but there were no differences(F=0.793, P=0.535; F=0.783, P=0.542). K1, K2, Km and Kmax decreased at each time point postoperatively compared with those preoperatively, but there were no differences(F=0.627, P=0.574; F=1.264, P=0.296; F=0.727, P=0.520; F=1.115, P=0.359). Anterior and posterior elevations at the thinnest point both decreased compared with those preoperatively, but the differences were not statistically significant(F=1.046, P=0.359; F=1.164, P=0.337). The non-contact intraocular pressure at each time point postoperatively was higher than that preoperatively, but the differences were not statistically significant(F=0.814, P=0.522). There were no differences in CCT and TCT at any time points of the follow-ups compared with those preoperatively(F=0.931, P=0.453; F=0.782, P=0.542). There was no difference in ECD at 12 mo postoperatively versus preoperative value(t=1.266, P=0.228). At 1 mo postoperatively, anterior segment optical coherence tomography(AS-OCT)exhibited an increase of density in the anterior stroma, and there was a demarcation line with an average depth of 124.07±25.13 μm.CONCLUSION: SC-A-TE-CXL can be considered as a surgical treatment for severe keratoconus, which can delay the progression of severe keratoconus with high safety. However, the long-term efficacy of this treatment requires further observation.
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Tyrosine kinase inhibitors （TKIs） represent a class of small-molecule targeted drugs that improve the survival time of patients with gastrointestinal stromal tumor （GIST）. Imatinib， sunitinib， regorafenib， ripretinib， and avapritinib are commonly used TKIs in the clinical treatment of various types of GIST. This article provides a comprehensive review of the pharmacokinetics and therapeutic drug monitoring （TDM） of these five drugs， finding that there is significant individual variability in the pharmacokinetics of these drugs. Among them， the absorption of imatinib， regorafenib， and avapritinib are influenced by food intake. Imatinib should be taken with meals and 200 mL of water， regorafenib is taken with a low-fat meal， while avapritinib is taken on an empty stomach. TKIs are mainly metabolized by cytochrome P450 3A4 （CYP3A4）， and when used in combination with CYP3A4 inducers or inhibitors， drug exposure levels will significantly change； apart from metabolic enzymes， the exposure levels of TKIs are also influenced by interactions with the transporter proteins P-glycoprotein and breast cancer resistance protein. Currently， research on TDM for TKIs is still in the exploratory stage， with a substantial amount of literature reporting the effective concentrations of imatinib， sunitinib and regorafenib. However， the precise relationship between exposure levels and efficacy/ toxicity needs further exploration. Currently， there is a lack of research on the correlation between exposure levels and efficacy/ toxicity of ripretinib and avapritinib. It is recommended to implement TDM in patients taking these drugs and explore their therapeutic window in combination with pharmacokinetic models. The commonly used methods for clinical TDM of TKIs include immunoassay， chromatography， and surface-enhanced Raman spectroscopy， providing a technical basis for clarifying the therapeutic window of TKIs.
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Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.
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Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.