Haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 21 young people with severe aplastic anemia (SAA) undergoing haplo-HSCT without T-cell-depleted. We observed that all patients had sustained hematopoietic engraftment without any adverse UC-MSC infusion-related events. Furthermore, we did not observe any increase in severe aGVHD. These data suggest that UC-MSCs, possibly thanks to their potent immunosuppressive effect on allo-reactive host T lymphocytes escaping the preparative regimen, reduce the risk of graft failure and severe GVHD in haplo-HSCT.
Objective
To explore whether MiR-129-5p participates in radiosensitivity of medullary thyroid cell MZ-CRC-1 by inhibiting the gene expression of high mobility group protein B1 (HMGB1).
Methods
The radioresistant cell line MZ-CRC-1/R was established from MZ-CRC-1. Cell survival fraction was analyzed by colony formation assay. The expressions of miR-129-5p in MZ-CRC-1 and MZ-CRC-1/R cells were detected by qRT-PCR. Cell viability was determined by MTT assay. Cell apoptosis was measured by flow cytometry. Dual-luciferase reporter assay was performed to confirm the relationship between miR-129-5p and HMGB1. Besides, the protein expressions of HMGB1 and p-AKt were evaluated by western blot.
Results
Compared with that of MZ-CRC-1 cells, the survival fraction of MZ-CRC-1/R cells was significantly increased (t=3.038, 4.330, 4.885, 4.568, P<0.05), the cell viability of MZ-CRC-1/R cells was also increased (t=3.637, 7.734, 11.896, 14.522, P<0.05), and the expression of miR-129-5p(0.26±0.03) was significantly decreased in MZ-CRC-1/R cells(1.00±0.06) (t=19.107, P<0.05). Compared with miR-NC-inhibitor group, cell viability was promoted and cell apoptosis was blocked in the miR-129-5p-inhibitor group (t=5.156, 6.005, 9.649, 8.659, P<0.05). Moreover, miR-129-5p mimic suppressed cell viability and enhanced cell apoptosis after irradiation (t=3.118, 5.034, 6.005, 7.488, 6.362, P<0.05). Overexpression of miR-129-5p inhibited the protein expressions of HMGB1 and p-AKt (t=9.325, 10.614, P<0.05). In addition, HMGB1 depletion rescued cell apoptosis that was reduced by miR-129-5p inhibitor in MZ-CRC-1 cells (t=6.700, P<0.05), while HMGB1 overexpression attenuated the effect of miR-129-5p upregulation on MZ-CRC-1/R cells (t=7.073, P<0.05).
Conclusions
miR-129-5p increased the radiosensitivity of medullary thyroid-like cell MZ-CRC-1 by inhibiting HMGB1.
Key words:
Medullary thyroid carcinoma cells; miR-129-5p; HMGB1; Radiosensitivity
To evaluate the immunophenotype of acute leukemia patients, the surface and cyto-plasmic antigen expression in 162 cases of acute leukemia were analyzed by multiparameter flow cytometry and CD45/SSC gating. The results showed that CD117 (94. 9%),CD13 (88. 5%) and CD33(70. 5%) were mainly expressed in ANLL patients; cCD79a(100%) ,CD19(92. 1%) were chiefly expressed in B-ALL patients, and in T-ALL patients, cCD3(100%) and CD2(83. 3%) were expressed; For the expression of lymphoid differentiation antigen Ly+ANLL, CD7 (56. 2%) and CD19(31. 2%) were chiefly found, and for myeloid antigen My+ALL, CD13(88. 9%) and CD33(27. 8%) were detected. In conclusion, multiparameter flow cytometry and three-color direct immunofluorescence staining methods may be of important clinical significance in diagnosis, therapy and prognosis of acute leukemia.
Adverse reactions are prone to occur in the early stage of chemotherapy and can negatively affect the dietary intake and nutritional status of breast cancer (BC) patients. Consequently, they need to participate in health self-management and lifestyle promotion programs. Early multidisciplinary interventions aim to enhance dietary management behavior and quality of life in chemotherapy-treated BC patients.
Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy). A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched. We were particularly interested in whether the dosage of Cy significantly impacted graft failure (GF) and overall survival (OS). All patients showed sustained hematopoietic engraftment without any increase in severe aGVHD and transplantation-related mortality (TRM). The incidences of grade II-IV aGVHD, grade III-IV aGVHD and extensive cGVHD were 18%, 10% and 7%, respectively. The probabilities of 1-year and 5-year OS were 93.1% and 87.9%, respectively. Furthermore, patient age <15 years, MNC cells >8×108/kg and donor age <45 years were associated with better survival (P=0.043, P=0.023, and P=0.037, respectively) and engraftment (P=0.019, P=0.008, and P=0.001, respectively). Our findings indicated that SAA patients lack MSD benefited the most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen. Improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.
Adverse effects during chemotherapy severely impact the daily diet of breast cancer (BC) patients. Engaging in dietary self-management is crucial for healthy lifestyle and recovery. This study aims to create the Dietary Self-management Behavior Questionnaire (DSMBQ) and preliminarily validate its reliability, validity, and discriminative ability for BC patients undergoing chemotherapy. The questionnaire was developed through a scoping review, patient interviews, and referenced to previous scales. The initial draft item pool underwent two rounds of Delphi expert consultations, creating the draft DSMBQ with 6 predefined dimensions and 98 items. Subsequently, the draft questionnaire underwent three rounds of investigation. The results from the first two surveys were utilized for item selection, the third was to assess the construct of the final DSMBQ. Three groups (n = 158, 385, and 771) were conveniently sampled from three hospitals in Xi'an and Zhengzhou cities. Lastly, 150, 378, and 760 participants, respectively, completed valid questionnaires. Exploratory factor analysis and variability analysis were used to assess the draft questionnaire, and the structure was further examined through confirmatory factor analysis. The final DSMBQ comprised 22 items organized into 4 dimensions. The cumulative variance contribution rate totaled 62.96%. The Cronbach's α demonstrated high internal consistency at 0.91, while the split-half reliability coefficient was 0.83, and the test-retest reliability coefficient reached 0.94. Correlation coefficients between the scores of each dimension and the total score ranged from 0.697 to 0.751. With the exception of the normed fit index (NFI) and the non-normed fit index (NNFI) at 0.89 (close to 0.90), all other indicators met statistical requirements. Patients exhibited varying average scores for each dimension of the DSMBQ based on differences in age, education level, Body Mass Index (BMI), menopausal status, and cancer stage (P < 0.05). The DSMBQ demonstrated good reliability, validation, and discriminative ability in Chinese BC patients undergoing chemotherapy. Tailored to the cultural context, the DSMBQ emerges as a high-quality tool for the nuanced assessment of dietary self-management in BC patients by focusing on lifestyle behavior changes. It holds the potential to enhance subjective initiative and confidence, facilitating increased patient participation in their healthcare.
Anaplastic thyroid carcinoma (ATC) has a poor prognosis due to its resistance to all conventional treatments. The long non‑coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) serves a critical role in cancer chemoresistance; however, whether NEAT1 is associated with chemoresistance of ATC remains unclear. In the present study, reverse transcription‑quantitative PCR assays were performed to detect the expression levels of NEAT1, microRNA (miR)‑9‑5p and sperm‑associated antigen 9 (SPAG9). Western blot analysis was conducted to assess the protein expression levels of p62, microtubule‑associated proteins 1A/1B light chain 3B and SPAG9. Cell proliferation was detected using the Cell Counting kit‑8 assay, and cell apoptosis was determined by flow cytometry. Dual‑luciferase reporter and RNA immunoprecipitation assays were performed to verify the interaction between NEAT1 and miR‑9‑5p, or miR‑9‑5p and SPAG9. Furthermore, an animal model was used to investigate the regulatory effects of NEAT1 on cisplatin (DDP)‑resistance in tumors in vivo. The present results demonstrated that NEAT1 was upregulated in ATC tissues and cell lines, and NEAT1 silencing resulted in decreased DDP‑resistance of ATC cells. In addition, NEAT1 suppressed miR‑9‑5p expression by binding to miR‑9‑5p and SPAG9 was a direct target of miR‑9‑5p. miR‑9‑5p overexpression sensitized ATC cells to DDP. Notably, NEAT1 silencing exerted its inhibitory effect on DDP‑resistance of ATC via the miR‑9‑5p/SPAG9 axis in vitro and in vivo. In conclusion, the present study demonstrated that NEAT1 silencing ameliorated DDP‑resistance of ATC, at least in part by reducing miR‑9‑5p sponging and regulating SPAG5 expression; therefore, NEAT1 may be considered a potential therapeutic target of ATC.
Chemotherapy often negatively impacts the nutritional status of breast cancer patients, and healthy dietary behaviors are important for patient wellbeing. With the guidance of the "Knowledge, Attitude and Practice model" (KAP model), the objective of this survey was to determine the frequency with which patients engage in healthy dietary behaviors and to explore the association between healthy dietary behaviors and nutrition literacy and dietary attitudes.This study included a total of 284 breast cancer patients undergoing chemotherapy from three hospitals spanning three cities in China. Face-to-face interviews were conducted to collect demographic and clinical characteristics as well as the Dietary Nutritional Knowledge, Attitude and Practice Questionnaire (DNKAPQ) and the Nutrition Literacy Measurement Scale for Chinese Adult (NLMS-CA).Participants exhibited medium to high scores for nutrition literacy, dietary attitude and dietary behavior. Nutrition literacy (r = 0.505, p < 0.001) and dietary attitude (r= 0.326, p < 0.001) scores were both positively correlated with the total dietary behavior score. The total nutrition literacy score was positively correlated with the total dietary behavior score (r = 0.286, p < 0.001). In the univariate analysis, age, body mass index, living environment, education level, monthly family income, work status, menopausal status, number of comorbidities, relapse and endocrine therapy were significantly associated with dietary behavior (p < 0.05). In the multiple linear regression analysis, patients' dietary behavior was significantly associated with nutrition literacy (β = 0.449, p < 0.001) and dietary attitude (β = 0.198, p < 0.001). These two factors accounted for 28.6% of the variation in the patients' dietary behavior scores.There is an important need for targeted dietary and nutritional interventions designed and implemented by health professionals to improve dietary behaviors. Intervention design and content should take the patients' nutrition literacy and dietary attitudes into consideration. In particular, women who are older, overweight, unemployed, and postmenopausal and live in rural areas, exhibit fewer comorbidities, have a lower family income and education level, have not relapsed and are currently receiving endocrine therapy are in urgent need of diet-specific intervention.
Objective To analysze the Immunophenotype of rabbit adipose-derived stem cells(ADSCs) and study the potential of ADSCs differentiating into cardiomyocytes-like and its probability of them for treating ischemic heart disease. Methods Cells were isolated from the fatty tissue of rabbits by enzyme digestion cultured in DMEM medium. Immunophenotype of Second-passaged cells were also treated with 10μmol/L 5-azacytidine for 24 hours. Then the medium was replaced with fresh medium and the cells were cultured for 3 weeks with the medium changed once 3 days. Later these cells were subjected to RT-PCR forα-MHC and immunofluorescence analysis for cTNT. Results ADSCs had u-nique immunophenotypes and they were high-expressed for Sca1, CD44, CD117 but low-expressed for CD34, CD45. After treatment with 5-azacytidine for 3 weeks, the ADSCs expressedα-MHC and cTNT. Conclusion These observations reveal that ADSC has the character of mesenchymal stem cell and confirm that ADSC can be induced into cardiomyocytes-like. Fatty tissue can potentially be a source of autologous cells for myocardial repair.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)