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1.
Ther Adv Hematol ; 15: 20406207241237602, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38558826

RESUMEN

Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is a severe early complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been shown that the intestinal microbiota plays a critical role in this process. As metabolites of the intestinal microbiota, short-chain fatty acids (SCFAs) are vital for maintaining the host-microbiota symbiotic equilibrium. This article provides an overview of the protective effect of SCFAs in the gastrointestinal tract, emphasizes their association with GI-aGVHD, and explores relevant research progress in prevention and treatment research.


Research advances on short-chain fatty acids in gastrointestinal acute graft-versus-host disease Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is a severe early complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been shown that the intestinal microbiota plays a critical role in this process. As metabolites of the intestinal microbiota, short-chain fatty acids (SCFAs) are vital for maintaining the host-microbiota symbiotic equilibrium. This article provides an overview of the protective effect of SCFAs in the gastrointestinal tract, emphasizes their association with GI-aGVHD and explores relevant research progress in prevention and treatment research.

2.
BMC Pediatr ; 24(1): 204, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519960

RESUMEN

BACKGROUND: Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process. METHODS: One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL. RESULTS: One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM-/FCM-), four (2.42%) were positive by both CM and FCM (CM+/FCM+), and thirty-three (20%) displayed a single positive finding by FCM (CM-/FCM+) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP+ had no CNS relapse, like those with TLP-. However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p < 0.05). CONCLUSIONS: We have validated that FCM is more accurate in stratifying the status of the CNS compared to CM analysis. However, to improve the EFS rate of childhood leukemia, it is necessary to combine CM examination, FCM, and cranial imaging for the early diagnosis of CNSL.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Citometría de Flujo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/diagnóstico , Recurrencia , China , Pronóstico
3.
Infect Drug Resist ; 16: 7455-7464, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38089959

RESUMEN

Background: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT. Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected. Results: The median age of the cohort was 7±3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p<0.05, Fisher's Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72-99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19. Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic's impact on their care.

4.
Front Chem ; 11: 1260165, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37780989

RESUMEN

Milletia pinnata oil and Nardostachys jatamansi are rich sources of bioactive compounds and have been utilized to formulate various herbal formulations, however, due to certain environmental conditions, pure extract form is prone to degradation. Therefore, in this, study, a green hydrodistillation technology was used to extract M. pinnata oil and N. jatamansi root for the further application in development of pectin crosslinked carboxymethyl cellulose/guar-gum nano hydrogel. Both oil and extract revealed the presence of spirojatamol and hexadecanoic acid methyl ester. Varied concentrations (w/w) of cross-linker and gelling agent were used to formulate oil emulsion extract gel (OEEG1, OEG1, OEEG2, OEG2, OEEG3, OEG3, OEEG4, OEG4, OEEG5, OEG5), in which OEEG2 and OEG2 were found to be stable. The hydrogel displayed an average droplet size of 186.7 nm and a zeta potential of -20.5 mV. Endo and exothermic peaks and the key functional groups including hydroxyl, amide II, and amide III groups confirmed thermal stability and molecular structure. The smooth surface confirmed structural uniformity. Bactericidal activity against both Gram-positive (25.41 ± 0.09 mm) and Gram-negative (27.25 ± 0.01 mm) bacteria and anti-inflammatory activity (49.25%-83.47%) makes nanohydrogel a potential option for treating various infections caused by pathogenic microorganisms. In conclusion, the use of green hydrodistillation technology can be used to extract the bioactive compounds that can be used in formulation of biocompatible and hydrophobic nanohydrogels. Their ability to absorb target-specific drugs makes them a potential option for treating various infections caused by pathogenic microorganisms.

5.
J Mater Chem B ; 11(44): 10613-10624, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37877316

RESUMEN

Immune checkpoint (ICP) blockade (ICB) is one of the most promising immunotherapies for acute myeloid leukemia (AML). However, owing to their heterogeneity, AML cells may cause uncoordinated metabolic fluxes and heterogeneous immune responses, inducing the release of a spatiotemporally sensitive immune response marker. Timely and in situ detection of immune responses in ICB therapy is important for therapeutic strategy adjustment. Herein, we constructed an all-in-one nanoprobe for self-driving ICB and simultaneously detecting an immune response in the same AML cell in vivo, thus enabling accurate evaluation of heterogenetic immune responses in living AML mice without additional drug treatment or probe processes. The nature-inspire polydopamine (PDA) nanoparticles loaded with an ICP blocker were targeted to the leukocyte immunoglobulin like receptor B4 (a new ICP) of AML cells to induce the release of immune response marker granzyme B (GrB). The PDA nanoparticles were additionally paired with carbon-derived graphene quantum dots (GQDs) to construct a full-organic 'turn-on' bionanoprobe that can transfer fluorescence resonance energy for GrB detection. This multifunctional nanoprobe was validated for triggering ICB therapy and monitoring the changes of GrB levels in real-time both in vitro and in vivo. The organic nanoprobe showed excellent permeability and retention in tumor cells and high biocompatibility in vivo. This bionanoprobe orderly interacted with the upstream ICP molecules and downstream signal molecule GrB, thereby achieving in situ immune response signals within the therapeutic efficacy evaluation window.


Asunto(s)
Leucemia Mieloide Aguda , Nanopartículas , Puntos Cuánticos , Ratones , Animales , Inhibidores de Puntos de Control Inmunológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Inmunidad
6.
Int J Environ Health Res ; : 1-14, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37879627

RESUMEN

In the present study, magnesium nanoparticles (Mg NPs) were synthesized utilizing an aqueous extract of Berberis aristate rhizome and evaluated for antimicrobial and anti-inflammatory activity. Technofunctional properties of rhizome powder were evaluated and during thermal stability evaluation four stages of decomposition with a maximum delta Y value of 76.04 % was observed. Optimization of Mg NPs was carried out by employing eight different concentrations (C1-C8) and the C4 showed maximum absorbance at 330 nm confirming the NPs synthesis. The Mg NPs showed the particle size of 62 nm, zeta potential of -24.7 mV and hexagonal mprphology. Potential inhibition against S. aureus and E. coli (76.78 ± 0.05% and 74.62 ± 0.17%)and anti-inflammatory activity ranging from 42.43 ± 0.07-82.92 ± 0.04% was observed for Mg NPs. Therefore, green synthesis of Mg NPs is a promising approach for the development ofbiological active NPs to cure microbial infections.

7.
Cancer Control ; 30: 10732748231187837, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37575028

RESUMEN

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neuroblastoma , Niño , Humanos , Estudios Retrospectivos , Trasplante Autólogo , Neuroblastoma/terapia , Pronóstico , Resultado del Tratamiento , Supervivencia sin Enfermedad
8.
Infect Drug Resist ; 16: 5501-5510, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37638069

RESUMEN

Purpose: The emergence of multi-drug resistant ESBL-producing E. coli poses a global health problem. In this study, we aimed to investigate the prevalence of E. coli infections and their antibiotic susceptibility profiles in paediatric clinical cases in Shenzhen, China from Jan 1, 2014, to Jan 30, 2019, while also determining temporal trends, identifying ESBL-producing strains, and recommending potential empirical antibiotic therapy options. Methods: We isolated a total of 4148 E. coli from different specimens from a single paediatric healthcare centre. Additionally, we obtained relevant demographic data from the hospital's electronic health records. Subsequently, we performed antimicrobial susceptibility testing for 8 classes of antibiotics and assessed ESBL production. Results: Out of the 4148 isolates, 2645 were from males. The highest burden of E. coli was observed in the age group of 0-1 years, which gradually declined over the five-year study period. Antimicrobial susceptibility results indicated that 82% of E. coli isolates were highly resistant to ampicillin, followed by 52.36% resistant to cefazolin and 47.46% resistant to trimethoprim/sulfamethoxazole. Notably, a high prevalence of ESBL production (49.54%) was observed among the E. coli isolates, with 60% of them displaying a multi-drug resistance phenotype. However, it is worth mentioning that a majority of the isolates remained susceptible to ertapenem and imipenem. Our findings also highlighted a decrease in E. coli infections in Shenzhen, primarily among hospitalized patients in the 0-1 year age group. However, this decline was accompanied by a considerably high rate of ESBL production and increasing resistance to multiple antibiotics. Conclusion: Our study underscores the urgent need for effective strategies to combat multi-drug resistant ESBL-producing E. coli Infections.

9.
J Glob Antimicrob Resist ; 34: 134-140, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37481113

RESUMEN

OBJECTIVES: Emergence of the plasmid-born mobile colistin resistance (mcr) gene is a growing concern in healthcare. Therefore, this study aimed to genomically characterise multidrug-resistant Escherichia coli and Klebsiella pneumoniae co-harbouring the mcr-1 and mcr-3 genes in young children. METHODS: E. coli (n = 3) and K. pneumoniae (n = 2) were collected from abdominal secretions and blood, respectively. The isolates were screened using tryptone soy broth with 4 µL/mL polymyxin-B. Growing bacteria were identified using the VITEK-2 system, matrix-assisted laser desorption/ionisation time-of-flight, and 16s RNA sequencing, followed by antibiotic susceptibility testing. Metallo-ß-lactamase (MBL) and extended-spectrum ß-lactamase (ESBL) production was also detected. Afterwards, strains were subjected to molecular screening targeting mcr variants and ESBL/MBL-encoding genes. Conjugation, pulsed-field gel electrophoresis, Southern hybridisation, multilocus sequence typing, and phylogenic group detection were performed, along with plasmid-genome sequencing and bioinformatics analysis. RESULTS: E. coli isolates (EC-19-322, 323, and 331) and K. pneumoniae isolates (KP-19-225 and 226) harboured both mcr-1 and mcr-3 genes. These strains were also found to be resistant to more than three classes of antibiotics. The conjugation experiment revealed the presence of mcr-1 and mcr-3 on a single plasmid, and the transmission frequency was 10-2 to 10-3. Both strains were found to be able to produce ESBLs and MBL. E. coli EC-19-322 and 323 were identified as ST131(O25a:H41); SP-19-331, as ST1577 (O16:H30); and K. pneumoniae, as ST231 (K2). All E. coli strains belonged to phylogenetic group B2, and the results of pulsed-field gel electrophoresis supported the multilocus sequence typing findings. CONCLUSION: This study reported the co-occurrence of mcr-1 and mcr-3 genes on a single plasmid in pathogenic ESBL/MBL-producing E. coli and K. pneumoniae isolated from young children.


Asunto(s)
Colistina , Escherichia coli , Humanos , Niño , Preescolar , Colistina/farmacología , Klebsiella pneumoniae/genética , Filogenia , Plásmidos/genética , beta-Lactamasas/genética , Genómica
10.
Front Cell Infect Microbiol ; 13: 1168096, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37293207

RESUMEN

Introduction: The emergence of multidrug-resistant Pseudomonas aeruginosa poses a global threat, but the distribution and resistance profiling are unclear, especially in young children. Infections due to P. aeruginosa are common, associated with high mortality, and increasingly ß-lactam drug resistant. Methods: We studied the molecular epidemiology and antibiotic resistance mechanisms in 294 clinicalisolates of P. aeruginosa from a pediatric hospital in China. Non-duplicate isolates were recovered from clinical cases and were identified using an API-20 kit followed by antimicrobial susceptibility testing using the VITEK®2 compact system (BioMerieux, France) and also by broth dilution method. In addition, a double-disc synergy test for the ESBL/E-test for MBL was performed. The presence of beta-lactamases, plasmid types, and sequence types was determined by PCR and sequencing. Results: Fifty-six percent (n = 164) of the isolates were resistant to piperacillin-tazobactam, followed by cefepime (40%; n = 117), ceftazidime (39%; n = 115), imipenem (36%; n = 106), meropenem (33%; n = 97), and ciprofloxacin (32%; n = 94). Forty-two percent (n = 126) of the isolates were positive for ESBL according to the double-disc synergy test. The blaCTX-M-15 cephalosporinase was observed in 32% (n = 40/126), while 26% (n = 33/126) werepositive for blaNDM-1 carbapenemase. Aminoglycoside resistance gene aac(3)IIIawas observed in 16% (n = 20/126), and glycylcyclines resistance gene tet(A) was observed in 12% (n = 15/126) of the isolates. A total of 23 sequence types were detected, including ST1963 (12%; n = 16), followed by ST381 (11%; n = 14), ST234 (10%; n = 13), ST145 (58%; n = 10), ST304 (57%; n = 9), ST663 (5%; n = 7), and a novel strain. In ESBL-producing P. aeruginosa, 12 different Incompatibility groups (Inc) were observed, the most common being IncFI, IncFIS, and IncA/C. The MOBP was the most common plasmid type, followed by MOBH, MOBF, and MOBQ. Discussion: Our data suggest that the spread of antibiotic resistance is likely due toclonal spread and dissemination of different clinical strains of P. aeruginosa harbouring different plasmids. This is a growing threat in hospitals particularly in young children which needs robust prevention strategies.


Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Niño , Preescolar , Pseudomonas aeruginosa/genética , Epidemiología Molecular , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , beta-Lactamasas/genética , beta-Lactamasas/uso terapéutico , Ceftazidima , Genómica , Células Clonales , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/tratamiento farmacológico
11.
ACS Nano ; 17(11): 10925-10937, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37219600

RESUMEN

Immunotherapy as an alternative treatment strategy for B-cell lymphoma is undesirable because of tumor heterogeneity and immune surveillance. Spermidine (SPM), as a regulator of the tumor microenvironment (TME), can facilitate the release of damage-associated molecular patterns (DAMPs) from cancer cells, promote immune recognition, and thus alleviate immune surveillance in the TME. Hence, in this work, self-assembled spermidine-based metal-immunopeptide nanocomplexes (APP-Fe NCs; APP is anti-programmed death ligand-1 peptide) with pH-responsive release kinetics were prepared via the flash nanocomplexation (FNC) technique based on the noncovalent interaction between APP-SPM-dextran (DEX) and sodium tripolyphosphate (TPP) and coordination between Fe3+ and TPP. An in vitro study suggested that APP-Fe NCs effectively induce strong oxidative stress and mitochondrial dysfunction and subsequently lead to ferroptosis in cells by interfering with homeostasis in lymphoma cells. Further investigation on lymphoma mice models demonstrated that APP-Fe NCs effectively inhibited the growth and liver metastasis of lymphomas. Mechanistically, by triggering ferroptosis in tumor tissues, these spermidine-containing APP-Fe NCs efficiently facilitated the release of DAMPs and ultimately reshaped TME to enhance immunotherapy efficacy in lymphoma. Combined with its good histocompatibility and facile preparation technique, this pH-responsive APP-Fe NCs with regulation on TME may hold potential for cascade amplification on the combinative immunotherapy of lymphoma in the clinic.


Asunto(s)
Linfoma , Neoplasias , Animales , Ratones , Espermidina/farmacología , Microambiente Tumoral , Linfoma/tratamiento farmacológico , Inmunoterapia , Alarminas , Línea Celular Tumoral
13.
Front Bioeng Biotechnol ; 11: 1138972, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37077226

RESUMEN

The number of patients with valvular heart disease is increasing yearly, and valve replacement is the most effective treatment, during which bioprosthetic heart valves (BHVs) are the most widely used. Commercial BHVs are mainly prepared with glutaraldehyde (Glut) cross-linked bovine pericardial or porcine aortic valves, but the residual free aldehyde groups in these tissues can cause calcification and cytotoxicity. Moreover, insufficient glycosaminoglycans (GAGs) in tissues can further reduce biocompatibility and durability. However, the anti-calcification performance and biocompatibility might be improved by blocking the free aldehyde groups and increasing the GAGs content in Glut-crosslinked tissues. In our study, adipic dihydrazide (ADH) was used to neutralize the residual free aldehyde groups in tissues and provide sites to blind with oligohyaluronan (OHA) to increase the content of GAGs in tissues. The modified bovine pericardium was evaluated for its content of residual aldehyde groups, the amount of OHA loaded, physical/chemical characteristics, biomechanical properties, biocompatibility, and in vivo anticalcification assay and endothelialization effects in juvenile Sprague-Dawley rats. The results showed that ADH could completely neutralize the free aldehyde groups in the Glut-crosslinked bovine pericardium, the amount of OHA loaded increased and the cytotoxicity was reduced. Moreover, the in vivo results also showed that the level of calcification and inflammatory response in the modified pericardial tissue was significantly reduced in a rat subcutaneous implantation model, and the results from the rat abdominal aorta vascular patch repair model further demonstrated the improved capability of the modified pericardial tissues for endothelialization. Furthermore, more α-SMA+ smooth muscle cells and fewer CD68+ macrophages infiltrated in the neointima of the modified pericardial patch. In summary, blocking free-aldehydes and loading OHA improved the anti-calcification, anti-inflammation and endothelialization properties of Glut-crosslinked BHVs and in particularly, this modified strategy may be a promising candidate for the next-generation of BHVs.

14.
Infect Drug Resist ; 16: 1567-1572, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969940

RESUMEN

Invasive fungal infections (IFIs) are among the most severe complications in recipients of hematopoietic stem cell transplantation (HSCT) recipients and in patients with hematological malignancies. An increasing number of uncommon fungal infections have been reported in this era of antifungal prophylaxis. Coprinopsis cinerea is a rare pathogen that causes opportunistic infections in the immunocompromised patients, including HSCT recipients and is associated with very high mortality rates. Herein, we present a successfully treated pediatric HSCT patient with breakthrough pulmonary IFI caused by Coprinopsis cinerea despite posaconazole, prophylaxis using multidisciplinary approaches.

15.
Med Sci Monit ; 29: e939724, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36748357

RESUMEN

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Senmin Chen, Xiuli Yuan, Huanli Xu, Meng Yi, Sixi Liu, Feiqiu Wen. WNT974 Inhibits Proliferation, Induces Apoptosis, and Enhances Chemosensitivity to Doxorubicin in Lymphoma Cells by Inhibiting Wnt/b-Catenin Signaling. Med Sci Monit, 2020; 26: e923799. DOI: 10.12659/MSM.923799.

17.
Clin Transl Med ; 13(1): e1175, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36683248

RESUMEN

BACKGROUND: Hematopoietic stem cells (HSCs) from different sources show varied repopulating capacity, and HSCs lose their stemness after long-time ex vivo culture. A deep understanding of these phenomena may provide helpful insights for HSCs. METHODS: Here, we applied single-cell RNA-seq (scRNA-seq) to analyse the naïve and stimulated human CD34+ cells from cord blood (CB) and mobilised peripheral blood (mPB). RESULTS: We collected over 16 000 high-quality single-cell data to construct a comprehensive inference map and characterised the HSCs under a quiescent state on the hierarchy top. Then, we compared HSCs in CB with those in mPB and HSCs of naïve samples to those of cultured samples, and identified stemness-related genes (SRGs) associated with cell source (CS-SRGs) and culture time (CT-SRGs), respectively. Interestingly, CS-SRGs and CT-SRGs share genes enriched in the signalling pathways such as mRNA catabolic process, translational initiation, ribonucleoprotein complex biogenesis and cotranslational protein targeting to membrane, suggesting dynamic protein translation and processing may be a common requirement for stemness maintenance. Meanwhile, CT-SRGs are enriched in pathways involved in glucocorticoid and corticosteroid response that affect HSCs homing and engraftment. In contrast, CS-SRGs specifically contain genes related to purine and ATP metabolic process, which is crucial for HSC homeostasis in the stress settings. Particularly, when CT-SRGs are used as reference genes for the construction of the development trajectory of CD34+ cells, lymphoid and myeloid lineages are clearly separated after HSCs/MPPs. Finally, we presented an application through a small-scale drug screening using Connectivity Map (CMap) against CT-SRGs. A small molecule, cucurbitacin I, was found to efficiently expand HSCs ex vivo while maintaining its stemness. CONCLUSIONS: Our findings provide new perspectives for understanding HSCs, and the strategy to identify candidate molecules through SRGs may be applicable to study other stem cells.


Asunto(s)
Diferenciación Celular , Sangre Fetal , Células Madre Hematopoyéticas , Humanos , Antígenos CD34/análisis , Sangre Fetal/citología , Células Madre Hematopoyéticas/citología , Análisis de la Célula Individual , Perfilación de la Expresión Génica , Diferenciación Celular/genética
18.
Transplant Cell Ther ; 29(2): 136.e1-136.e7, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36402457

RESUMEN

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplantation teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplantation teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (37%) and acute lymphoblastic leukemia (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (13%). The peripheral blood stem cell source accounted for 41% of HIDs and 75% of matched sibling donors. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and total body irradiation-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.


Asunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Humanos , SARS-CoV-2 , Médula Ósea , Pueblos del Este de Asia , Pandemias , COVID-19/epidemiología , Sistema de Registros
19.
Brief Bioinform ; 24(1)2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36575567

RESUMEN

Long noncoding ribonucleic acids (RNAs; LncRNAs) endowed with both protein-coding and noncoding functions are referred to as 'dual functional lncRNAs'. Recently, dual functional lncRNAs have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell-type-specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncRNAs. Here, we developed a deep-learning model with a multi-head self-attention mechanism, LncReader, to identify dual functional lncRNAs. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncRNAdb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with RNA-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncRNA identification.


Asunto(s)
ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/química , RNA-Seq
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