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1.
J Clin Immunol ; 44(5): 118, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758417

RESUMEN

Deficiency of Adenosine Deaminase 2 (DADA2) patients presenting with primary immunodeficiency are at risk of uncontrolled EBV infection and secondary malignancies including EBV-related lymphoproliferative disorders (LPD). This paper describes the first case of EBV related diffuse large B-cell lymphoma in a patient with DADA2 and uncontrolled EBV infection. Consideration should be given to monitoring for EBV viraemia and to preventative EBV specific therapy in DADA2 and patients with at risk primary immunodeficiencies. A type I interferon (IFN) gene signature is associated with DADA2 though its association with immune dysregulation is unclear.


Asunto(s)
Adenosina Desaminasa , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/etiología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Femenino , Enfermedades Autoinflamatorias Hereditarias
2.
J Chem Phys ; 161(6)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39136663

RESUMEN

X-ray photoelectron spectroscopy, reflection-absorption infrared spectroscopy, and temperature-programmed reaction/desorption have been employed to investigate the reaction of CH3-CHCl-C(=O)Cl on Cu (100), with the aid of density functional theory (DFT) calculations. Experimentally, CH3-CH=C=O (methylketene) is found to be the product from the dechlorination of CH3-CHCl-C(=O)Cl on Cu(100) at 120 K. The CH3-CH=C=O generated on the surface would dimerize to form 2,4-dimethylcyclobutane-1,3-dione below 180 K. In agreement with the experimental findings, our DFT molecular dynamics simulations demonstrate that the dechlorination of CH3-CHCl-C(=O)Cl, resulting in CH3-CH=C=O and two Cl atoms, occurs readily, completing within 0.6 ps at 300 K. The simulations also indicate that the cleavage of the CH-Cl bond precedes that of the C(=O)-Cl bond. The static DFT calculations suggest that the dimerization of CH3-CH=C=O primarily occurs through the coupling of two C=C bonds, which has a lower barrier of 38.08 kJ mol-1 compared to the 69.05 kJ mol-1 barrier for C=C + C=O coupling.

3.
Pain Manag Nurs ; 25(3): 308-315, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38278750

RESUMEN

BACKGROUND: Despite the significant impact of chemotherapy-induced peripheral neuropathy on the quality of life for breast cancer survivors, there is a notable lack of comprehensive research. Therefore, a crucial need exists for further systematic investigation and inquiry into this matter. AIMS: This study examined predictors of quality of life in breast cancer survivors with chemotherapy-induced peripheral neuropathy. DESIGN: A cross-sectional, correlational design. SETTINGS: This study was conducted at a medical center in northern Taiwan and a teaching hospital in northeastern Taiwan. PARTICIPANTS/SUBJECTS: One hundred and thirty adult women with breast cancer, who have undergone chemotherapy and obtained a Total Neuropathy Scale-Clinical Version score>0, were enrolled. METHODS: Neuropathic pain, sleep disturbances, depression, and quality of life were evaluated using multiple regression analysis to identify quality of life predictors. Clinical importance was established using the minimally important difference of Functional Assessment of Cancer Therapy-Breast. RESULTS: The study indicated that improving depression (B = -10.87, p < .001) and neuropathic pain (B = -8.33, p = .004) may enhance the quality of life of breast cancer survivors with chemotherapy-induced peripheral neuropathy. Moreover, the individual's marital status and family history of breast cancer were identified as predictive factors. CONCLUSIONS: This study illuminates quality of life determinants for breast cancer survivors with chemotherapy-induced peripheral neuropathy, advocating comprehensive care and addressing depression and neuropathic pain for better outcomes.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Supervivientes de Cáncer , Neuralgia , Calidad de Vida , Humanos , Femenino , Calidad de Vida/psicología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/psicología , Estudios Transversales , Persona de Mediana Edad , Neuralgia/psicología , Neuralgia/inducido químicamente , Supervivientes de Cáncer/psicología , Supervivientes de Cáncer/estadística & datos numéricos , Taiwán , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Anciano , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/psicología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Encuestas y Cuestionarios
4.
J Formos Med Assoc ; 123(3): 325-330, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38097427

RESUMEN

AIMS: Advanced maternal age (AMA) is correlated with higher risk of adverse pregnancy outcomes while the pathophysiology remains unclear. Our study aimed to investigate whether AMA is linked to the clustering of metabolic abnormalities, which in turn is associated with an increased risk of adverse pregnancy outcomes. METHOD: A total of 857 pregnant woman were recruited in a prospective cohort at National Taiwan University Hospital, from November 2013 to April 2018. Metabolic abnormalities during pregnancy were defined as following: fasting plasma glucose ≥92 mg/dl, body mass index (BMI) ≥24 kg/m2, plasma high-density lipoprotein cholesterol <50 mg/dl, hyper-triglyceridemia (≥140 mg/dl in the first trimester or ≥220 mg/dl in the second trimester), and blood pressure ≥130/85 mmHg. RESULT: Incidence of large for gestational age (LGA), primary caesarean section (CS), and the presence of any adverse pregnancy outcome increased with age. The advanced-age group tended to have more metabolic abnormalities in both the first and the second trimesters. There was a significant association between the number of metabolic abnormalities in the first and the second trimesters and the incidence of LGA, gestational hypertension or preeclampsia, primary CS, preterm birth, and the presence of any adverse pregnancy outcome, adjusted for maternal age. CONCLUSION: AMA is associated with clustering of metabolic abnormalities during pregnancy, and clustering of metabolic abnormalities is correlated with increased risk of adverse pregnancy outcomes.


Asunto(s)
Resultado del Embarazo , Nacimiento Prematuro , Embarazo , Recién Nacido , Humanos , Femenino , Resultado del Embarazo/epidemiología , Estudios Prospectivos , Edad Materna , Cesárea , Nacimiento Prematuro/epidemiología
5.
Int J Mol Sci ; 25(14)2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39063198

RESUMEN

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau (MAPT) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort.


Asunto(s)
Moléculas de Adhesión Celular Neuronal , Inmunoglobulina G , Humanos , Moléculas de Adhesión Celular Neuronal/inmunología , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Tauopatías/inmunología , Tauopatías/genética , Tauopatías/metabolismo , Animales , Proteínas tau/inmunología , Proteínas tau/metabolismo , Proteínas tau/genética , Autoanticuerpos/inmunología
6.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38339136

RESUMEN

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.


Asunto(s)
Melanoma , Animales , Femenino , Humanos , Células Endoteliales/metabolismo , Macrófagos/metabolismo , Melanoma/metabolismo , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Microambiente Tumoral , Ratones
7.
Mol Pain ; 19: 17448069231210423, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37845039

RESUMEN

Traumatic neuropathic pain (TNP) is caused by traumatic damage to the somatosensory system and induces the presentation of allodynia and hyperalgesia. Mitochondrial dysfunction, neuroinflammation, and apoptosis are hallmarks in the pathogenesis of TNP. Recently, mitochondria-based therapy has emerged as a potential therapeutic intervention for diseases related to mitochondrial dysfunction. However, the therapeutic effectiveness of mitochondrial transplantation (MT) on TNP has rarely been investigated. Here, we validated the efficacy of MT in treating TNP. Both in vivo and in vitro TNP models by conducting an L5 spinal nerve ligation in rats and exposing the primary dorsal root ganglion (DRG) neurons to capsaicin, respectively, were applied in this study. The MT was operated by administrating 100 µg of soleus-derived allogeneic mitochondria into the ipsilateral L5 DRG in vivo and the culture medium in vitro. Results showed that the viable transplanted mitochondria migrated into the rats' spinal cord and sciatic nerve. MT alleviated the nerve ligation-induced mechanical and thermal pain hypersensitivity. The nerve ligation-induced glial activation and the expression of pro-inflammatory cytokines and apoptotic markers in the spinal cord were also repressed by MT. Consistently, exogenous mitochondria reversed the capsaicin-induced reduction of mitochondrial membrane potential and expression of pro-inflammatory cytokines and apoptotic markers in the primary DRG neurons in vitro. Our findings suggest that MT mitigates the spinal nerve ligation-induced apoptosis and neuroinflammation, potentially playing a role in providing neuroprotection against TNP.


Asunto(s)
Capsaicina , Neuralgia , Ratas , Animales , Capsaicina/farmacología , Capsaicina/uso terapéutico , Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Neuralgia/metabolismo , Nervios Espinales/metabolismo , Hiperalgesia/metabolismo , Ganglios Espinales/metabolismo , Ligadura/efectos adversos , Citocinas/metabolismo , Apoptosis
8.
Am J Obstet Gynecol ; 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38036165

RESUMEN

BACKGROUND: Whether myomectomy increases the risk of placenta accreta spectrum in the following pregnancies remains controversial. OBJECTIVE: This study aimed to investigate the effect of myomectomy on the risk of placenta accreta spectrum in the following pregnancies. Moreover, different methods of myomectomy on the risk of placenta accreta spectrum were explored. STUDY DESIGN: A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database, including all pregnant patients in Taiwan who gave birth between January 2008 and December 2017. A 1:1 propensity score estimation matching was performed for the analysis of myomectomy on the risk of placenta accreta spectrum. Among pregnant patients who received myomectomy, different methods of myomectomy on the risk of placenta accreta spectrum were compared with the control group. RESULTS: Among the 1,371,458 pregnant patients in this study, 11,255 pregnant patients had a history of myomectomy. The risk of placenta accreta spectrum was higher in pregnant patients with a history of myomectomy than in pregnant patients without a history of myomectomy (incidence: 0.96% vs 0.20%; adjusted odds ratio, 2.28; 95% confidence interval, 1.85-2.81; P<.01). Among pregnant patients with a history of myomectomy, 5045 (46.87%) received laparotomic myomectomy, 3973 (36.93%) received laparoscopic myomectomy, and 1742 (16.20%) received hysteroscopic myomectomy. The incidence of placenta accreta spectrum was higher in the hysteroscopic group than in the laparotomic group or the laparoscopic group (1.89% [hysteroscopic group] vs 0.71% [laparotomic group] and 0.81% [laparoscopic group]; P<.05). Compared with patients without a history of myomectomy, the adjusted odds ratio for placenta accreta spectrum was 3.88 (95% confidence interval, 2.68-5.63; P<.05) in the hysteroscopic group. CONCLUSION: Myomectomy, especially hysteroscopic myomectomy, is associated with an increased risk of placenta accreta spectrum in the subsequent pregnancy.

9.
Support Care Cancer ; 32(1): 40, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38110567

RESUMEN

PURPOSE: This study explored symptom clusters (SCs) and predominant symptoms in lymphoma survivorships at least 1 month after treatment. METHODS: A cross-sectional trend study design was adopted. Inclusion criteria were participants who were over the age of 20, diagnosed with lymphoma, and 1 month after treatment concluded. The symptoms were assessed by the Functional Assessment of Cancer Therapy Scale-Lymphoma Subscale. Data were analyzed using descriptive statistics, latent profile analysis (LPA), and comparisons of means and frequencies of each symptom in each SC. RESULTS: A total of 234 lymphoma survivors completed this study. Three SCs were identified at < 2 and > 5 years and two SCs at 2-5 years. Worrying about getting new symptoms and infections emerged as predominant symptoms across all SCs over time. This study provides insights into the symptom experiences of survivors of lymphoma and highlights the significant role of worry-related symptoms in their survivorship. CONCLUSION: Through the use of LPA and a trend study design, we identified distinct SCs in lymphoma survivors, providing valuable insights into their longitudinal symptom experiences. The findings emphasize the complexity of symptomatology in lymphoma survivorship and underscore the importance of employing advanced statistical methods to explore and understand these clusters comprehensively, informing targeted interventions and improved care strategies.


Asunto(s)
Linfoma , Supervivencia , Humanos , Estudios Transversales , Síndrome , Linfoma/terapia , Sobrevivientes , Calidad de Vida
10.
Int J Mol Sci ; 24(14)2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37511415

RESUMEN

Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral Sinularia flexibilis and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFß, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFß-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFß and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFß-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFß activities. In addition, SC-1 inhibits TGFß-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis.


Asunto(s)
Antozoos , Carcinoma , Animales , FN-kappa B/metabolismo , Interleucina-6/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta/genética , Antozoos/metabolismo
11.
Molecules ; 28(4)2023 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-36838713

RESUMEN

Cancer stemness is the process by which cancer cells acquire chemoresistance and self-renewal in the tumor microenvironment. Glucose-regulated protein 78 (GRP78) is a biomarker for gastric cancer and is involved in cancer stemness. By inducing cancer stemness in various types of cancer, the polarization of macrophages into tumor-associated macrophages (TAMs) controls tumor progression. Betulinic acid (BA) is a bioactive natural compound with anticancer properties. However, whether GRP78 regulates TAM-mediated cancer stemness in the tumor microenvironment and whether BA inhibits GRP78-mediated cancer stemness in gastric cancer remain unknown. In this study, we investigated the role of GRP78 in gastric cancer stemness in a tumor microenvironment regulated by BA. The results indicated that BA inhibited not only GRP78-mediated stemness-related protein expression and GRP78-TGF-ß-mediated macrophage polarization into TAMs, but also TAM-mediated cancer stemness. Therefore, BA is a promising candidate for clinical application in combination-chemotherapy targeting cancer stemness.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Ácido Betulínico , Chaperón BiP del Retículo Endoplásmico , Factor de Crecimiento Transformador beta1/metabolismo , Transducción de Señal , Macrófagos/metabolismo , Microambiente Tumoral
12.
Curr Issues Mol Biol ; 44(12): 6145-6157, 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36547080

RESUMEN

Exosomes containing glucose-regulated protein 78 (GRP78) are involved in cancer malignancy. GRP78 is thought to promote the tumor microenvironment, leading to angiogenesis. No direct evidence for this role has been reported, however, mainly because of difficulties in accurately measuring the GRP78 concentration in the exosomes. Recently, exosomal GRP78 concentrations were successfully measured using an ultrasensitive ELISA. In the present study, GRP78 concentrations in exosomes collected from gastric cancer AGS cells with overexpression of GRP78 (OE), knockdown of GRP78 (KD), or mock GRP78 (mock) were quantified. These three types of exosomes were then incubated with vascular endothelial cells to examine their effects on endothelial cell angiogenesis. Based on the results of a tube formation assay, GRP78-OE exosomes accelerated angiogenesis compared with GRP78-KD or GRP78-mock exosomes. To investigate the mechanisms underlying this effect, we examined the Ser473 phosphorylation state ratio of AKT, which is involved in the angiogenesis process, and found that AKT phosphorylation was increased by GRP78-OE exosome application to the endothelial cells. An MTT assay showed that GRP78-OE exosome treatment increased the proliferation rate of endothelial cells, and a wound healing assay showed that this treatment increased the migration capacity of the endothelial cells. These findings demonstrated that GRP78-containing exosomes promote the tumor microenvironment and induce angiogenesis.

13.
Scand J Immunol ; 95(4): e13133, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34942025

RESUMEN

INTRODUCTION: Anti-Golgi antibodies (AGAs) are rare antibodies that are found as distinct, polarised cytoplasmic staining on the HEp-2 substrate. METHODS: We performed a review of patients that demonstrated this autoantibody in a large laboratory cohort in Australia. Over a 24-month period, all patients that had a sample submitted for routine antinuclear antibodies (ANAs) that had AGA staining were retrospectively identified. Medical records were perused to identify clinical associations. RESULTS: There were 23 813 ANAs identified with 34 patients (0.14%) demonstrating AGA staining. AGAs were found in a variety of inflammatory disorders, malignancies and liver diseases. They did not associate with any other significant ANA, and in contrast with previous studies, we did not find any association with systemic autoimmune rheumatic diseases. CONCLUSIONS: Anti-Golgi antibodies are rare, non-specific and possibly a bystander phenomenon. Future studies are required to study the origin and longitudinal clinical associations of these autoantibodies.


Asunto(s)
Anticuerpos Antinucleares , Enfermedades Autoinmunes , Autoanticuerpos , Estudios de Cohortes , Aparato de Golgi , Humanos , Estudios Retrospectivos
14.
Anal Biochem ; 654: 114831, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35921878

RESUMEN

Exosomes transfer molecules horizontally to surrounding cells and therefore have a key role in cancer progression. To clarify the role of exosomes in cancer progression, trace amounts of proteins in their lumen and membrane fractions should be analyzed separately. For this purpose, an adequate and easy-to-use method of separating the lumen and membrane fractions of exosomes must be developed. Further, because exosomes contain only trace amounts of proteins, an ultrasensitive protein detection method is necessary. To develop an adequate and easy-to-use lumen and membrane fraction separation method, we applied a commercially available kit originally developed for cells to exosomes and examined the validity of the results compared with those obtained using a conventional, complicated Na2CO3 method. To develop an ultrasensitive protein detection method, we designated GRP78, which is upregulated in cancer cells and contributes to cancer progression, as the target protein and detected it at the subattomolar level using an ultrasensitive ELISA combined with thio-NAD cycling. By applying these methods together, GRP78 was successfully quantified in both the lumen and membrane fractions of exosomes obtained from cultured cancer cells. The present results will facilitate studies to broaden our understanding of the tumor microenvironment.


Asunto(s)
Exosomas , Neoplasias , Ensayo de Inmunoadsorción Enzimática/métodos , Exosomas/metabolismo , Membranas , Neoplasias/metabolismo
15.
Int J Med Sci ; 19(6): 1036-1046, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35813297

RESUMEN

Background: Acute lung injuries (ALI) cause disruption of the alveolar-capillary barrier and is the leading cause of death in critically ill patients. This study tested the hypothesis that the administration of freshly isolated viable allogeneic mitochondria can prevent alveolar-capillary barrier injuries at the endothelial level, as mitochondrial dysfunction of the pulmonary endothelium is a critical aspect of ALI progression. Methods: ALI was induced by intratracheal lipopolysaccharide instillation (LPS, 1mg/kg) in anesthetized rats. Mitochondria (100 µg) were isolated from the freshly harvested soleus muscles of naïve rats and stained with a green fluorescence MitoTracker™ dyne. A mitochondria or placebo solution was randomly administered into the jugular veins of the rats at 2 h and 4 h after ALI induction. An arterial blood gas analysis was done 20 h later. The animals were then sacrificed and lung tissues were harvested for analysis. Results: An IVIS Spectrum imaging system was used to obtain ex vivo heart-lung block images and track the enhancement of MitoTracker™ fluorescence in the lungs. Mitochondria transplantation significantly improved arterial oxygen contents (PaO2 and SaO2) and reduced CO2 tension in rats with ALI. Animals with mitochondrial transplants had significantly higher ATP concentrations in their lung tissues. Allogeneic mitochondria transplantation preserved alveolar-capillary barrier function, as shown by a reduction in protein levels in the bronchoalveolar lavage fluid and decreased extravasated Evans blue dyne and hemoglobin content in lung tissues. In addition, relaxation responses to acetylcholine and eNOS expression were potentiated in injured pulmonary arteries and inflammatory cells infiltration into lung tissue was reduced following mitochondrial transplantation. Conclusions: Transplantation of viable mitochondria protects the integrity of endothelial lining of the alveolar-capillary barrier, thereby improving gas exchange during the acute stages of endotoxin-induced ALI. However, the long-term effects of mitochondrial transplantation on pulmonary function recovery after ALI requires further investigation.


Asunto(s)
Lesión Pulmonar Aguda , Trasplante de Células Madre Hematopoyéticas , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/terapia , Animales , Permeabilidad Capilar , Endotoxinas , Lipopolisacáridos/metabolismo , Pulmón , Mitocondrias/metabolismo , Ratas
16.
Gut ; 70(2): 243-250, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32792335

RESUMEN

OBJECTIVE: Although mass eradication of Helicobacter pylori has been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear. DESIGN: Mass eradication of H. pylori infection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalent H. pylori infection. Test positives for the 13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively. RESULTS: After six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates of H. pylori fell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, p<0.001) and 25% (95% CI -14% to 51%, p=0.18), respectively. No significant changes were noted in the incidence rates of other digestive tract cancers or the antibiotic resistance rate of H. pylori. CONCLUSION: Population-based eradication of H. pylori has significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period. TRIAL REGISTRATION NUMBER: NCT00155389.


Asunto(s)
Erradicación de la Enfermedad , Infecciones por Helicobacter/prevención & control , Helicobacter pylori , Neoplasias Gástricas/prevención & control , Antibacterianos/uso terapéutico , Erradicación de la Enfermedad/métodos , Femenino , Gastroscopía , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Humanos , Incidencia , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/mortalidad , Taiwán/epidemiología
17.
Curr Issues Mol Biol ; 44(1): 63-72, 2021 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-35723384

RESUMEN

Chemotherapy is the treatment of choice for gastric cancer, but the currently available therapeutic drugs have limited efficacy. Studies have suggested that gastric cancer stem cells may play a key role in drug resistance in chemotherapy. Therefore, new agents that selectively target gastric cancer stem cells in gastric tumors are urgently required. Sirtuin-3 (SIRT3) is a deacetylase that regulates mitochondrial metabolic homeostasis to maintain stemness in glioma stem cells. Targeting the mitochondrial protein SIRT3 may provide a novel therapeutic option for gastric cancer treatment. However, the mechanism by which stemness is regulated through SIRT3 inhibition in gastric cancer remains unknown. We evaluated the stemness inhibition ability of the SIRT3 inhibitor 4'-bromo-resveratrol (4-BR), an analog of resveratrol in human gastric cancer cells. Our results suggested that 4-BR inhibited gastric cancer cell stemness through the SIRT3-c-Jun N-terminal kinase pathway and may aid in gastric cancer stem-cell-targeted therapy.

18.
J Clin Immunol ; 41(8): 1915-1935, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34657246

RESUMEN

PURPOSE: Deficiency of adenosine deaminase type 2 (ADA2) (DADA2) is a rare inborn error of immunity caused by deleterious biallelic mutations in ADA2. Clinical manifestations are diverse, ranging from severe vasculopathy with lacunar strokes to immunodeficiency with viral infections, hypogammaglobulinemia and bone marrow failure. Limited data are available on the phenotype and function of leukocytes from DADA2 patients. The aim of this study was to perform in-depth immunophenotyping and functional analysis of the impact of DADA2 on human lymphocytes. METHODS: In-depth immunophenotyping and functional analyses were performed on ten patients with confirmed DADA2 and compared to heterozygous carriers of pathogenic ADA2 mutations and normal healthy controls. RESULTS: The median age of the patients was 10 years (mean 20.7 years, range 1-44 years). Four out of ten patients were on treatment with steroids and/or etanercept or other immunosuppressives. We confirmed a defect in terminal B cell differentiation in DADA2 and reveal a block in B cell development in the bone marrow at the pro-B to pre-B cell stage. We also show impaired differentiation of CD4+ and CD8+ memory T cells, accelerated exhaustion/senescence, and impaired survival and granzyme production by ADA2 deficient CD8+ T cells. Unconventional T cells (i.e. iNKT, MAIT, Vδ2+ γδT) were diminished whereas pro-inflammatory monocytes and CD56bright immature NK cells were increased. Expression of the IFN-induced lectin SIGLEC1 was increased on all monocyte subsets in DADA2 patients compared to healthy donors. Interestingly, the phenotype and function of lymphocytes from healthy heterozygous carriers were often intermediate to that of healthy donors and ADA2-deficient patients. CONCLUSION: Extended immunophenotyping in DADA2 patients shows a complex immunophenotype. Our findings provide insight into the cellular mechanisms underlying some of the complex and heterogenous clinical features of DADA2. More research is needed to design targeted therapy to prevent viral infections in these patients with excessive inflammation as the overarching phenotype.


Asunto(s)
Agammaglobulinemia/inmunología , Linfocitos B/inmunología , Inmunodeficiencia Combinada Grave/inmunología , Linfocitos T/inmunología , Adenosina Desaminasa/sangre , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Adolescente , Adulto , Agammaglobulinemia/sangre , Agammaglobulinemia/genética , Anciano , Diferenciación Celular , Niño , Preescolar , Células Dendríticas/inmunología , Humanos , Lactante , Péptidos y Proteínas de Señalización Intercelular/sangre , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Péptidos y Proteínas de Señalización Intercelular/genética , Células Asesinas Naturales/inmunología , Persona de Mediana Edad , Inmunodeficiencia Combinada Grave/sangre , Inmunodeficiencia Combinada Grave/genética , Adulto Joven
19.
J Gastroenterol Hepatol ; 36(3): 671-679, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32671873

RESUMEN

BACKGROUND AND AIM: The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. METHODS: Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. RESULTS: Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). CONCLUSIONS: After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.


Asunto(s)
Gastritis/tratamiento farmacológico , Gastritis/microbiología , Infecciones por Helicobacter , Helicobacter pylori , Medición de Riesgo/métodos , Neoplasias Gástricas/etiología , Biomarcadores/metabolismo , Metilación de ADN , Reacciones Falso Negativas , Femenino , Mucosa Gástrica/metabolismo , Gastritis/diagnóstico , Gastritis/genética , Humanos , Masculino , MicroARNs/metabolismo , Pepsinógeno A/metabolismo , Riesgo , Factores de Riesgo , Pruebas Serológicas , Índice de Severidad de la Enfermedad
20.
Support Care Cancer ; 29(6): 2959-2971, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33025227

RESUMEN

PURPOSE: This study aimed to prospectively explore severity and prevalence of chemotherapy-induced peripheral neuropathy (CIPN) and examine the correlation between clinician-assessed (objective) and patient-reported (subjective) CIPN in breast cancer survivors receiving taxane. METHODS: This was a prospective, longitudinal study. Purposive sampling was adapted to enroll women newly diagnosed with breast cancer and about to receive taxane. The CIPN was assessed after breast cancer diagnosed and before chemotherapy (T1), before cycle 1 to 4 taxane infusion (T2 to T5), and after chemotherapy completion (T6 to T8). Total Neuropathy Score-clinical version (TNSc), Identification Pain Questionnaire (ID pain), Functional Assessment of Cancer Therapy-Taxane subscale (FACT-Tax), and Peripheral Neuropathy Scale (PNS) were utilized for measuring CIPN. Descriptive statistics, Pearson correlation coefficient, and generalized estimating equation were used to analyze data. RESULTS: A total of 88 participants were included. Both clinician-assessed and patient-reported CIPN gradually increased between T1 and T6 and mildly decreased at T7 and T8. Fifty-five participants (62.5%) experienced CIPN at T8. Weak-to-moderate correlations between subjective and objective CIPN were found at T6 to T8 (r = 0.272-0.533, p < 0.05). The change of TNSc, FACT-Tax, and PNS were significant over time. However, the significant change of neuropathic pain was only found at T6. CONCLUSION: The change of CIPN prevalence and severity were significant over time in survivors newly diagnosed with breast cancer. Specifically, the severest and highest CIPN was detected at chemotherapy completion. Survivors remained suffering from CIPN 3 months after chemotherapy completion. Besides, mild to moderate correlations between clinician-assessed and patient-reported CIPN were identified.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Hidrocarburos Aromáticos con Puentes/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Taxoides/efectos adversos , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Supervivientes de Cáncer , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Estudios Prospectivos
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