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1.
Arch Toxicol ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096369

RESUMEN

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.

2.
Acta Pharmacol Sin ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060523

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

3.
Nano Lett ; 24(28): 8752-8762, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38953881

RESUMEN

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Ratones , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Microesferas , Terapia Fototérmica , Neumonía Estafilocócica/terapia , Terapia de Fagos/métodos , Verde de Indocianina/química , Verde de Indocianina/farmacología , Verde de Indocianina/uso terapéutico , Verde de Indocianina/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Administración por Inhalación , Humanos , Bacteriófagos/química
4.
Am J Hematol ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037279

RESUMEN

Alpha-thalassemia is an inherited blood disorder caused by impaired α-globin chain production, leading to anemia and other complications. Hemoglobin H (HbH) disease is caused by a combination of mutations generally affecting the expression of three of four α-globin alleles; disease severity is highly heterogeneous, largely driven by genotype. Notably, non-deletional mutations cause a greater degree of ineffective erythropoiesis and hemolysis, higher transfusion burden, and increased complication risks versus deletional mutations. There are limited treatment options for HbH disease, and effective therapies are needed. This review discusses the pathophysiology of HbH disease, current management strategies, unmet needs, and emerging treatment options.

5.
Chem Commun (Camb) ; 60(60): 7721-7724, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38967357

RESUMEN

A method for the synthesis of furans bearing indoline skeletons was developed via an intramolecular palladium-catalyzed 5-exo-dig cyclization/etherification cascade of N-propargyl arylamines containing a 1,3-dicarbonyl side chain. This method realized the first capture of vinyl carbopalladiums by ketones as O-nucleophiles and showed a wide range of substrate tolerability affording trisubstituted furans in various yields. The enantioselective version for this domino process and diverse derivatizations of the reaction products were also studied.

6.
Plant Sci ; 347: 112183, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972549

RESUMEN

The normal progression of mitotic cycles and synchronized development within female reproductive organs are pivotal for sexual reproduction in plants. Nevertheless, our understanding of the genetic regulation governing mitotic cycles during the haploid phase of higher plants remains limited. In this study, we characterized RNA HELICASE 32 (RH32), which plays an essential role in female gametogenesis in Arabidopsis. The rh32 heterozygous mutant was semi-sterile, whereas the homozygous mutant was nonviable. The rh32 mutant allele could be transmitted through the male gametophyte, but not the female gametophyte. Phenotypic analysis revealed impaired mitotic progression, synchronization, and cell specification in rh32 female gametophytes, causing the arrest of embryo sacs. In the delayed pollination test, none of the retarded embryo sacs developed into functional female gametophytes, and the vast majority of rh32 female gametophytes were defective in the formation of the large central vacuole. RH32 is strongly expressed in the embryo sac. Knock-down of RH32 resulted in the accumulation of unprocessed 18 S pre-rRNA, implying that RH32 is involved in ribosome synthesis. Based on these findings, we propose that RH32 plays a role in ribosome synthesis, which is critical for multiple processes in female gametophyte development.

7.
Heliyon ; 10(12): e32595, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38988518

RESUMEN

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

8.
Heliyon ; 10(12): e33132, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39022094

RESUMEN

Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.

9.
Pediatr Blood Cancer ; 71(9): e31176, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38967585

RESUMEN

INTRODUCTION: Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. Our aim was to identify prognostic genetic markers for patients with neuroblastoma, who were treated with the Taiwan Pediatric Oncology Group (TPOG) neuroblastoma N2002 protocol, to improve risk stratification and inform treatment. METHODS: Our analysis was based on 53 primary neuroblastoma specimens, diagnosed pre-chemotherapy, and 11 paired tumor relapse specimens. Deep sequencing of 113 target genes was performed using a custom panel. Multiplex ligation-dependent probe amplification was performed to identify clinical outcomes related to copy-number variations. RESULTS: We identified 128 variations associated with survival, with the number of variations being higher in the relapse than that in the diagnostic specimen (p = .03). The risk of event and mortality was higher among patients with a tumor mutational burden ≥10 than that in patients with a lower burden (p < .0001). Multivariate analysis identified tumor mutational burden, MYCN amplification, and chromosome 3p deletion as significant prognostic factors, independent of age at diagnosis, sex, and tumor stage. The 5-year event-free survival and overall survival rate was lower among patients with high tumor burden than in patients with low tumor burden. Furthermore, there was no survival of patients with an ALK F1147L variation at 5 years after diagnosis. CONCLUSIONS: Genome sequencing to determine the tumor mutational burden and ALK variations can improve the risk classification of neuroblastoma and inform treatment.


Asunto(s)
Mutación , Neuroblastoma , Humanos , Neuroblastoma/genética , Neuroblastoma/mortalidad , Neuroblastoma/patología , Masculino , Femenino , Preescolar , Lactante , Niño , Pronóstico , Biomarcadores de Tumor/genética , Tasa de Supervivencia , Estudios de Seguimiento , Variaciones en el Número de Copia de ADN , Carga Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adolescente
10.
J Geriatr Cardiol ; 21(5): 506-522, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38948898

RESUMEN

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

11.
Front Immunol ; 15: 1409637, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076987

RESUMEN

Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy defined by clinical progression for more than 2 months. 16-20% of CIDP patients may present with rapidly progressive weakness that resembles GBS, known as acute-onset CIDP (A-CIDP). However, it is challenging to distinguish from GBS-TRF because of their similar clinical symptom and features. In this case review, we report a patient with A-CIDP with the detection of anti-GM3 and anti-sulfatides antibodies, which rarely have been in A-CIDP and may account for her progressive and recurrent symptoms. Methods: We analyzed existing medical literature and described a clinical case of A-CIDP with antibodies positive. Results: We reported a 56-year-old female presented with bilateral lower extremity weakness and distal numbness. She experienced similar symptoms four times and responded well to the IVIg therapy. Lumbar puncture demonstrated albumin-cytologic dissociation and EDX examination revealed multiple peripheral nerve damage. After ruling out other demyelination diseases, a diagnosis of A-CIDP was made. Discussion: The antiganglioside and anti-sulfatide antibodies are involved in CIDP pathogenesis and can help to distinguish A-CIDP and other variants. To prevent secondary damage, it is important to monitor relapse and remission symptoms along the treatment line. A rare case of A-CIDP is discussed concerning the detection of anti-GM3 and anti-sulfatides antibodies, thus making a retrospective comparison of antibodies in some literature to understand A-CIDP better.


Asunto(s)
Autoanticuerpos , Gangliósido G(M3) , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Humanos , Femenino , Persona de Mediana Edad , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/inmunología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Gangliósido G(M3)/inmunología , Gangliósido G(M3)/análogos & derivados , Sulfoglicoesfingolípidos/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Diagnóstico Diferencial
12.
Sci Rep ; 14(1): 15956, 2024 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987349

RESUMEN

With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, 'Xusuan No. 6' was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.


Asunto(s)
Ajo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico , Transcriptoma , Ajo/genética , Ajo/metabolismo , Respuesta al Choque Térmico/genética , Ontología de Genes , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
13.
World J Orthop ; 15(7): 642-649, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39070933

RESUMEN

BACKGROUND: Tibial avulsion fractures of the posterior cruciate ligament (PCL) are challenging to treat and compromise knee stability and function. Traditional open surgery often requires extensive soft tissue dissection, which may increase the risk of morbidity. In response to these concerns, arthroscopic techniques have been evolving. The aim of this study was to introduce a modified arthroscopic technique utilizing an M-shaped suture fixation method for the treatment of tibial avulsion fractures of the PCL and to evaluate its outcomes through a case series. AIM: To evaluate the effects of arthroscopic M-shaped suture fixation on treating tibia avulsion fractures of the PCL. METHODS: We developed a modified arthroscopic M-shaped suture fixation technique for tibia avulsion fractures of the PCL. This case series included 18 patients who underwent the procedure between January 2021 and December 2022. The patients were assessed for range of motion (ROM), Lysholm score and International knee documentation committee (IKDC) score. Postoperative complications were also recorded. RESULTS: The patients were followed for a mean of 13.83 ± 2.33 months. All patients showed radiographic union. At the final follow-up, all patients had full ROM and a negative posterior drawer test. The mean Lysholm score significantly improved from 45.28 ± 8.92 preoperatively to 91.83 ± 4.18 at the final follow-up (P < 0.001), and the mean IKDC score improved from 41.98 ± 6.06 preoperatively to 90.89 ± 5.32 at the final follow-up (P < 0.001). CONCLUSION: The modified arthroscopic M-shaped suture fixation technique is a reliable and effective treatment for tibia avulsion fractures of the PCL, with excellent fracture healing and functional recovery.

14.
Lancet Haematol ; 11(8): e580-e592, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39002551

RESUMEN

BACKGROUND: Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD. METHODS: In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m2 twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing. FINDINGS: Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment discontinuation), one due to Aspergillus infection, one due to septic shock, and one due to acute respiratory distress syndrome; none were considered to be related to study drug. INTERPRETATION: Pending final analysis, this study suggests that ruxolitinib is active and well tolerated in both treatment-naive and corticosteroid-refractory patients aged 2 years to younger than 18 years with chronic GVHD, thereby supporting its use in this patient population. The safety profile of ruxolitinib in this patient population is consistent with that of adults. Final analysis of this study will provide further information on the long-term benefits of ruxolitinib in children with chronic GVHD. FUNDING: Novartis.


Asunto(s)
Corticoesteroides , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Nitrilos , Pirazoles , Pirimidinas , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Corticoesteroides/uso terapéutico , Enfermedad Crónica , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirimidinas/uso terapéutico , Resultado del Tratamiento
15.
Stem Cell Res ; 79: 103490, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39002250

RESUMEN

Epilepsy is a chronic neurological disease. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as epilepsy caused by ATP1A2 gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSC line (SDCHi007-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original ATP1A2 gene mutation.


Asunto(s)
Epilepsia , Células Madre Pluripotentes Inducidas , Factor 4 Similar a Kruppel , Mutación , ATPasa Intercambiadora de Sodio-Potasio , Células Madre Pluripotentes Inducidas/metabolismo , Humanos , Epilepsia/genética , Epilepsia/patología , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Diferenciación Celular , Línea Celular , Masculino
16.
World J Gastroenterol ; 30(20): 2638-2656, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38855150

RESUMEN

As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.


Asunto(s)
Biomarcadores de Tumor , Detección Precoz del Cáncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/epidemiología , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Pronóstico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer/métodos , China/epidemiología , Incidencia , Factores de Riesgo
17.
Opt Express ; 32(8): 14541-14554, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859396

RESUMEN

This study proposes an ultraviolet-visible composite optical target simulation technique based on a liquid crystal display (LCD) spatial light modulation device to solve the problem of not being able to satisfy the demand for optical target simulation for both ultraviolet and visible light operating spectral ranges in a single system when composite simulation of multi-source spatial targets is performed. We establish a composite light source model of an ultraviolet light emitting diode (LED) and a xenon lamp to enhance the energy simulation of the ultraviolet portion, and the light is mixed and homogenized by an integrating sphere. We analyze the light transmission principle of LCD display devices and derive the equation for the relationship between its working band and transmittance. We design a transmission-type projection system with a wide spectral range and simulate the transmittance of the whole system, and demonstrate the optical target simulator can realize the simulation requirements of a wide working spectral range, high interstellar angular distance accuracy, and high magnitude accuracy.

18.
Opt Express ; 32(12): 21820-21836, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38859527

RESUMEN

Current space target simulation systems suffer from limitations, such as a single simulated spectral band, inability to allocate spectral ratios between bands, and poor imaging quality of multi-spectral simulated images. We propose a multi-source information fusion spatial target simulation method system that features a "series-parallel" hybrid connection. We optimize the design of a multi-spectral common aperture optical system and experimentally verify the proposed method. The experimental results show that the proposed system can simulate a wide range of spectral bands ranging from ultraviolet to long-wave infrared. Furthermore, it achieves precise control over the ratio of simulated radiant energy among spectral bands, with a spectral simulation error of less than 4.8%. Notably, it effectively images stars against the cosmic background and spacecraft across different spectral bands. This system serves as a theoretical cornerstone and provides crucial technological support for performance testing and rapid iterative development of multi-source information fusion space exploration systems.

19.
J Asian Nat Prod Res ; : 1-9, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38860546

RESUMEN

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

20.
Sleep Breath ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861133

RESUMEN

PURPOSE: To investigate the impact of obstructive sleep apnea (OSA) on postoperative delirium (PD), and evaluate the effectiveness of positive airway pressure (PAP) therapy on PD among OSA patients. METHODS: We systematically searched Embase, Cochrane Library and PubMed databases from their establishment to November 27, 2022. A random-effects approach was employed to determine aggregated results. Subgroup and sensitivity analyses were carried out to investigate heterogeneity. RESULTS: Sixteen eligible studies were included in the analysis. Thirteen studies revealed that OSA significantly elevated the likelihood of developing PD (OR = 1.71; 95%CI = 1.17 to 2.49; p = 0.005). Subgroup analysis according to delirium assessment scales showed that OSA did not exhibit an association with the incidence of PD assessed by the Confusion Assessment Method-Intensive Care Unit (OR = 1.14; 95%CI = 0.77 to 1.67; p = 0.51) but enhanced the likelihood of developing PD evaluated with other measurement scales (OR = 2.15; 95%CI = 1.44 to 3.19; p = 0.0002). Three additional studies explored the impact of PAP treatment on PD among OSA individuals, indicating no significant reduction in PD incidence with PAP use (OR = 0.58; 95%CI = 0.13 to 2.47; p = 0.46). CONCLUSIONS: OSA may not be a risk factor for PD in critically ill patients in the intensive care unit, but may increase the likelihood of developing PD among individuals receiving regular care in the ward postoperatively. The efficacy of PAP therapy in decreasing PD incidence among OSA patients remains debatable.

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