RESUMEN
Tumor cells engage with the immune system in a complex manner, utilizing evasion and adaptability mechanisms. The development of cancer and resistance to treatment relies on the ability of immune cells to adjust their phenotype and function in response to cues from the tumor microenvironment, known as immunological cell plasticity. This study delves into the role of long non-coding RNAs (lncRNAs) in enhancing immune cell flexibility in cancer, focusing on their regulatory actions in the tumor microenvironment and potential therapeutic implications. Through a comprehensive review of existing literature, the study analyzes the impact of lncRNAs on macrophages, T-cells, and MDSCs, as well as the influence of cytokines and growth factors like TNF, IL-6, HGF, and TGFß on immunological cell plasticity and tumor immunoediting. LncRNAs exert a strong influence on immune cell plasticity through mechanisms such as transcriptional regulation, post-transcriptional modifications, and chromatin remodeling. These RNA molecules intricately modulate gene expression networks, acting as scaffolding, decoys, guides, and sponges. Moreover, both direct cell-cell interactions and soluble chemicals in the tumor microenvironment contribute to enhancing immune cell activation and survival. Understanding the influence of lncRNAs on immune cell flexibility sheds light on the biological pathways of immune evasion and cancer progression. Targeting long non-coding RNAs holds promise for amplifying anti-tumor immunity and overcoming drug resistance in cancer treatment. However, further research is necessary to determine the therapeutic potential of manipulating lncRNAs in the tumor microenvironment.
RESUMEN
Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.
Asunto(s)
Anticuerpos Antiprotozoarios , Malaria Vivax , Células B de Memoria , Proteína 1 de Superficie de Merozoito , Plasmodium vivax , Plasmodium vivax/inmunología , Humanos , Malaria Vivax/inmunología , Anticuerpos Antiprotozoarios/inmunología , Animales , Proteína 1 de Superficie de Merozoito/inmunología , Ratones , Células B de Memoria/inmunología , Inmunidad Humoral/inmunología , Biomarcadores/sangre , Femenino , Memoria Inmunológica/inmunología , Linfocitos B/inmunología , Antígenos de Protozoos/inmunologíaRESUMEN
OBJECTIVE: Ruxolitinib was recently approved to treat corticosteroid-resistant acute graft-versus-host disease (GvHD). However, it is unknown as to whether starting ruxolitinib at a lower versus higher acute GvHD grade or earlier versus later affected outcomes. This study identified the impact of starting acute GvHD grade and start time after declaring corticosteroid resistance and the effect on complete and overall response rates to ruxolitinib therapy. METHODS: Retrospective, observational multi-center study. We divided cohorts into starting ruxolitinib ≤ 7 days (N = 45) versus at > 7 days after declaring corticosteroid resistance (N = 24). RESULTS: In ≤ 7 days cohort complete response (CR) rates at day 28 were 69% (54, 81%) versus 25% (11, 47%; p = .001) in > 7 days cohort, and overall response (OR) rates were 91% (78, 96%) versus 80% (48, 92%; p = .25). CONCLUSIONS: Our data suggest that starting ruxolitinib in ≤ 7 days of declaring corticosteroid failure regardless of G vHD grade improves complete response rate but not OR rates. Starting ruxolitinib at grade I and within 7 days may get a more significant response.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Nitrilos , Pirazoles , Pirimidinas , Humanos , Estudios Retrospectivos , Corticoesteroides/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
[This corrects the article DOI: 10.3389/fmed.2022.948945.].
RESUMEN
BACKGROUND: Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps. METHODS: A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry. RESULTS: Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L- T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RIIimmunized mice. CONCLUSIONS: PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities.
Asunto(s)
Malaria , Plasmodium ovale , Animales , Ratones , Plasmodium ovale/genética , Interferón gamma/genética , Linfocitos T CD8-positivos , Variaciones en el Número de Copia de ADN , Dominios Proteicos , Malaria/prevención & controlRESUMEN
BACKGROUND: Immunogenic cell death (ICD)is a kind of regulatory cell death, which causes a series of antigen-specific adaptive immune responses by generating and emitting some danger signals or damage-associated molecular patterns (DAMPs). At present, little is known about the prognostic value of ICD and its related processes in acute myeloid leukemia (AML). The aim of the study was to explore the relationship between ICD and tumor immune microenvironment changes in AML. RESEARCH DESIGN & METHODS: In the study, AML samples were divided into two groups by consensus clustering analysis, and then gene enrichment analysis and GSEA analysis were performed on the ICD high expression group. Furthermore, CIBERSORT was used to analyze the tumor microenvironment and immune characteristics of AML. Finally, a prognostic model related to ICD was constructed by using univariate and multivariate regression analysis. RESULTS: ICD was divided into two groups according to the level of ICD gene expression. The ICD high expression group was associated with good clinical results and high levels of immune cell infiltration. CONCLUSIONS: The study constructed and verified the prognostic characteristics of AML related to ICD, which has important value in predicting the overall survival time of AML patients.
Asunto(s)
Muerte Celular Inmunogénica , Leucemia Mieloide Aguda , Humanos , Pronóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: The aim of this systematic review and meta-analysis was to introduce the relatively novel method of ultrasound-guided local lauromacrogol injection (USG-LLI) followed by dilatation and curettage for caesarean scar pregnancy (CSP) and to investigate the clinical safety and efficacy between uterine artery embolization (UAE) and USG-LLI in the treatment of CSP. METHODS: The relevant literature and articles about USG-LLI, UAE and CSP published in eight electronic databases were searched to extract the primary outcomes for the selected articles. Review Manager Software(RevMan) V.5.2 was used for quantitative data synthesis and data analysis. Forest plots, sensitivity analysis and bias analysis were also performed on the included articles. RESULTS: Of 10 studies included in our search, 623 patients were in the USG-LLI group and 627 patients were in the UAE groups. There were no significant differences between the two groups in terms of success rate, blood loss and time to human chorionic gonadotropin (hCG) normalization. However, USG-LLI group patients than UAE group patients had a shorter duration of hospital stay (mean difference [MD] = -1.97; 95% confidence intervals [CI] -2.63 to -1.31; P < 0.05; I2 = 95%), shorter restored menses (MD = -4.84; 95%CI -5.78 to -3.90; P < 0.05; I2 = 95%), and lower complication rates [odds ratio(OR) = 0.21; 95%CI:0.15 to 0.30; P < 0.05]; and cheaper on expenses of hospitalization (MD = -8028.29; 95%CI -10,311.18 to -5745.40; P < 0.05; I2 = 100%). CONCLUSIONS: The results demonstrate that USG-LLI is comparable in curative effect and success rates with UAE in the therapy of CSP, but patients in the USG-LLI group seem to have fewer complications rates, shorter duration of hospital stays and lower costs.
Asunto(s)
Cicatriz , Embolización de la Arteria Uterina , Femenino , Embarazo , Humanos , Polidocanol , Cicatriz/etiología , Cicatriz/terapia , Embolización de la Arteria Uterina/efectos adversos , Ultrasonografía Intervencional , Cesárea/efectos adversosRESUMEN
Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.
Asunto(s)
Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Ascitis/genética , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/secundario , Peritoneo/patología , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: To evaluate the effect of addition of ruxolitinib in Graft-versus-Host Disease (GVHD) prophylaxis on pediatric patients with ß-thalassemia major after allogeneic hematopoietic stem cell transplantation(HSCT). METHODS: This retrospective study reviewed 49 consecutive ß-thalassemia major pediatric patients who underwent HSCT from unrelated or haploidentical donors from February 2018 to October 2022. All transplantation recipients received cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate (MTX) as GVHD prophylaxis; while 27 of them in the ruxolitinib group had added ruxolitinib oral to GVHD prophylaxis regimen at 2.5 mg twice daily once successful engraftment after January 2020. RESULTS: The outcome showed that the ruxolitinib group had a lower cumulative incidence than the control group regardless of acute GVHD (22.2% vs.40.9%; p = .153) or chronic GVHD (18.5% vs.40.9%; p = .072); especially, the incidence of grade III-IV acute GVHD was reported significantly less frequently in ruxolitinib group than that of the control group (0 vs. 27.3%, p = .005). No significant difference was detected between the two groups in EBV (Epstein-Barr virus)/CMV (cytomegalovirus) reactivation and BKV (BK virus) infection (p = .703, 1.000, and .436, respectively). Twenty-six patients (96.3%) in the ruxolitinib group were alive, while two patients (9.1%) in the control group died of intestinal acute GVHD. The 2-year overall survival (OS) and thalassemia-free survival (TFS) were both 96.296% in the ruxolitinib group, while both 90.909% in the control group. CONCLUSION: This study reveals that ruxolitinib prophylaxis is a promising option to decrease the incidence of grade III-IV acute GVHD in pediatric patients with ß-thalassemia major.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Talasemia beta , Humanos , Niño , Estudios Retrospectivos , Talasemia beta/complicaciones , Talasemia beta/terapia , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
HLA-DPB1*1352:01 differs from HLA-DPB1*02:01:02:01 by one nucleotide in exon 4.
Asunto(s)
Pueblos del Este de Asia , Nucleótidos , Humanos , AlelosRESUMEN
Objective: The previous study has indicated the fertility-enhancing effect of oil-based contrast agents during hysterosalpingography (HSG) in infertile patients. However, the variation of this effect with the time frame is seldom reported. The current study aimed to explore fertility improvement using oil-based contrast agents and the change of this improvement during the 3-year follow-up period in infertile patients. Materials and methods: Infertile women who underwent HSG with oil-based contrast agents (N = 500) or water-based contrast agents (N = 500) were enrolled. Spontaneous pregnancy rate and time to pregnancy were assessed at months (M)1, M2, M3, M6, M12, M24, and M36 after HSG. Results: The spontaneous pregnancy rate was 79% in the oil-based group and 70.2% in the water-based group. The cumulative spontaneous pregnancy rate was increased in the oil-based group when compared with the water-based group (p = 0.015). Fertility-enhancing effect of HSG was increased in the oil-based group when compared with the water-based group at all time points {M1 [odds ratio (OR)]: 1.536}; M2 (OR: 1.455); M3 (OR: 1.494); M6 (OR: 1.356); M9 (OR: 1.288); M12 (OR: 1.249); M24 (OR: 1.131); and M36 (OR: 1.125). While this superiority of the fertility-enhancing effect of HSG in the oil-based group (vs. the water-based group) was decreased with the time frame. Similar findings were also observed based on the physiological cycles. Conclusion: The HSG procedure with oil-based contrast agents shows a fertility-enhancing effect when compared to water-based contrast agents. This improvement could last at least 1 year while dropping to the normal level within the subsequent 2 years.
RESUMEN
BACKGROUND: BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system (CNS) leukemia. CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration. It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement. CASE SUMMARY: We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis, with no involvement in peripheral blood or bone marrow. Identification of abnormal phenotypes of blast cells, and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia. The patient received a combination of intrathecal therapy and high-dose chemotherapy. But the benefits of the treatments were short-lived and she experienced recurrence. CONCLUSION: Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy. New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.
RESUMEN
Recurrent spontaneous abortion (RSA) is a kind of pathological pregnancy, and abnormal function of trophoblast cells may be related to a variety of pregnancy complications including RSA. Psoralen is an effective ingredient extracted from Cullen corylifolium (L.) Medik. with multiple bioactivities mainly including anti-osteoporotic, anti-tumor, anti-inflammatory, and estrogen-like effects. However, the exact role of psoralen on trophoblast invasiveness has not been investigated thus far. In the present study, the effects of psoralen on the proliferation, migration, and invasion abilities of HTR-8/SVneo cells were evaluated by the CCK-8 and Transwell assays. The expression patterns of nuclear factor κB (NF-κB)/p65 and metalloproteinases (MMP)-2 and MMP-9 were characterized by further experiments including real-time quantitative polymerase chain reaction and Western blot. Indirect immunofluorescence was applied to track the NF-κB p65 translocation. Herein, we found that cell viability and invasive ability were promoted by psoralen in a concentration-dependent manner. Psoralen concentration-dependently enhanced both MMP-2 and MMP-9 expression and their activity of HTR-8/SVneo cells. Additionally, we observed accelerated nuclear accumulation and enhanced nuclear translocation of p65 in the presence of psoralen. Furthermore, invasiveness enhancement of psoralen on HTR-8/SVneo cells was partly eliminated by a NF-κB pathway inhibitor. Thus, our findings suggest that psoralen may serve as a potential repurpose drug candidate that can be used to induce migration and invasion of trophoblast cells through strengthening the NF-κB pathway.
RESUMEN
OBJECTIVE: To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation. METHODS: The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups. RESULTS: The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups. CONCLUSION: Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Talasemia , Talasemia beta , Niño , Preescolar , Enfermedad Injerto contra Huésped/complicaciones , Humanos , Calidad de Vida , Estudios Retrospectivos , Talasemia/terapia , Talasemia beta/terapiaRESUMEN
OBJECTIVE: To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients. METHODS: The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed. RESULTS: Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively. CONCLUSION: The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.
Asunto(s)
Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Talasemia , Niño , Humanos , Padres , Estudios Retrospectivos , Talasemia/terapia , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , ViremiaRESUMEN
Objective: This meta-analysis is aimed at systematically assessing the efficacy and prognosis of hemodialysis (HD) and peritoneal dialysis (PD) in the treatment of end-stage renal disease (ESRD). Methods: China National Knowledge Infrastructure, VIP, SinoMed, Cochrane Library, PubMed, and Embase databases were searched for relevant studies to evaluate the two different dialysis methods for ESRD. The search time was set from 2010 to 2021. Meta-analysis was performed using Stata16.0. The treatment group received PD, while the control group was given HD. Results: Out of 317 articles initially retrieved, 14 studies were finally included in our meta-analysis. The analysis results showed that there was no marked difference in the 1-year survival rate between the two groups (RR = 1.05; 95% CI: 1.00, 1.10; P > 0.05), but the incidence rate of adverse reactions in the treatment group was significantly lower than that in the control group (RR = 0.51; 95% CI: 0.37, 0.70; P < 0.05). In addition, PD and HD treatments caused significant decreases in serum creatinine levels (PD, SMD = -2.91; 95% CI: -3.79, -2.04; P < 0.05; HD, SMD = -3.09; 95% CI: -4.01, -2.16; P < 0.05) and blood urea nitrogen levels (PD, SMD = -2.54, 95% CI: -3.37, -1.72, P < 0.05; HD, SMD = -2.62, 95% CI: -3.47, -1.77, P < 0.05); however, there was no significant statistical difference in posttreatment levels of serum creatinine and blood urea nitrogen between the two groups. Compared with the control group, the hemoglobin (SMD = 0.56, 95% CI: 0.07, 1.06; P < 0.05) and serum albumin (SMD = 1.11, 95% CI: 0.46, 1.76, P < 0.05) levels were significantly increased in the treatment group after treatment. Conclusion: In summary, both PD and HD can improve renal function in uremic patients, but PD is superior to HD in reducing the incidence of adverse reactions, improving the nutritional status, and therefore improving the quality of life of patients.
Asunto(s)
Fallo Renal Crónico , Diálisis Peritoneal , Humanos , Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Pronóstico , Calidad de Vida , Diálisis Renal/efectos adversosRESUMEN
Six children with steroid resistant graft versus host disease (GVHD) after hematopoietic stem cell transplantation admitted in the hospital, including 4 cases of acute GVHD and 2 cases of chronic GVHD. Among the 4 acute GVHD cases, the main manifestations were large area rash and fever in 2 cases, and abdominal pain and diarrhea in 2 cases. In 2 chronic GVHD cases, one presented lichenoid dermatosis, and the other showed repeated oral ulcers with difficult mouth opening. Patients received tocilizumab (8 mg/kg per dose every 3 weeks) and ruxolitinib (5-10 mg/d, 28 d), at least 2 courses were completed. All patients had complete responses (100%), and 5 patients responded after completion of two treatment courses, with the median time of remission was 26.7 d. The median follow-up period was 11 (7-25) months, and no severe treatment-related adverse reactions were observed.
Asunto(s)
Síndrome de Bronquiolitis Obliterante , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Niño , Esteroides/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiologíaRESUMEN
RATIONALE: Polymyositis (PM) is a rare neuromuscular phenotype of chronic graft-versus-host disease (cGVHD). Although glucocorticoids have been shown to be effective in the treatment of PM, most people experience poor treatment response and poor prognosis. PATIENT CONCERNS: A six-year-old boy with thalassemia received allogeneic hematopoietic stem cell transplantation (HSCT) and consequently developed sudden myasthenia of limbs 17âmonths after the transplant. DIAGNOSES: Medical history, current symptoms, laboratory examinations, and imaging findings of the patient indicated cGVHD complicated with PM. INTERVENTIONS: He was then given high-dose corticosteroid therapy, including tacrolimus, ruxolitinib, and rituximab. OUTCOMES: Twenty-three months after transplantation, creatine kinase levels returned to normal range, and the MRI showed that the original muscle edema signal was significantly improved. The patient's muscle weakness continued to improve, and his overall condition was good. LESSONS: This report suggests that glucocorticoids combined with immunosuppressants may be effective against polymyositis. Rituximab and ruxolitinib may be a good choice in treating polymyositis.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Polimiositis/etiología , Talasemia beta/terapia , Niño , Glucocorticoides/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Masculino , Músculo Esquelético/patología , Polimiositis/tratamiento farmacológicoRESUMEN
Telomere length (TL) is a highly relevant biomarker for age-associated diseases and cancer, yet its clinical applications have been hindered by the inability of existing methods to rapidly measure the TL distribution and the percentage of chromosomes with critically short telomeres (CSTs, < 3 kb). Herein, we report the development of a high-throughput method to measure TL at the single-chromosome level. Metaphase chromosomes are isolated, hybridized with the Alexa Fluor 488-labeled telomeric peptide nucleic acid probe, and analyzed using a laboratory-built ultrasensitive nano-flow cytometer. The fluorescence intensity of individual chromosomes is converted to TL in kilobases upon external calibration. With an analysis rate of several thousand chromosomes per minute, a statistically robust TL distribution histogram is acquired in minutes, and the percentage of chromosomes with CSTs can be quickly assessed. By analyzing peripheral blood lymphocytes of 158 healthy donors, TL is found to shorten with age at a rate of 64 ± 3 bp/year and the percentage of chromosomes with CSTs increases with age at a rate of 0.32 ± 0.02%/year. Moreover, the data of 28 patients with chronic myeloid leukemia (CML) indicate that telomeres are significantly shorter at the time of diagnosis and the clinical phases of CML are closely associated with TL and the percentage of chromosomes with CSTs. This powerful tool could greatly deepen our understanding of telomere biology and improve the clinical utility of telomere biomarkers.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Telómero , Citometría de Flujo , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Telómero/genéticaRESUMEN
BACKGROUND: Cervical cancer is one of the most common gynecologic tumors. Evidence is accumulating that long non-coding RNAs participate in the pathogenesis of cancers, but the expression and role of lncRNA LINC00313 in cervical carcinoma is not reported. METHODS: We measured the expression levels of LINC00313 in clinical samples of cervical carcinoma and investigated the function of LINC00313 in the regulation of proliferation, metastasis, and EMT. Luciferase reporter assay was employed to explore the molecular regulation process of LINC00313. RESULTS: Our data showed that the levels of LINC00313 in cervical carcinoma tissues and cells were significantly up-regulated. Functionally, LINC00313 accelerated the progression, migration, and EMT of SiHa and Hela cells. Luciferase reporter assay confirmed that miR-4677-3p/CDK6 regulatory axis is the direct downstream of LINC00313. Functional gain- and loss-of-function strategies further showed that LINC00313 induced the up-regulation of CDK6 expression through competitive binding with miR-4677-3p, leading to promote the progression of cervical carcinoma. CONCLUSION: Our results demonstrated that LINC00313 accelerated the progression of cervical cancer through the miR-4677-3p/CDK6 regulatory axis. LncRNA LINC00313 may serve as a potential target for the diagnosis and treatment of cervical carcinoma.