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1.
Nano Lett ; 24(8): 2457-2464, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38373157

RESUMEN

The ability of living objects to respond rapidly en masse to various stimuli or stress is an important function in response to externally applied changes in the local environment. This occurs across many length scales, for instance, bacteria swarming in response to different stimuli or stress and macromolecular crowding within cells. Currently there are few mechanisms to induce similar autonomous behaviors within populations of synthetic protocells. Herein, we report a system in which populations of individual objects behave in a coordinated manner in response to changes in the energetic environment by the emergent self-organization of large object swarms. These swarms contain protocell populations of approximately 60 000 individuals. We demonstrate the dissipative nature of the hierarchical constructs, which persist under appropriate UV stimulation. Finally, we identify the ability of the object populations to change behaviors in an adaptive population-wide response to the local energetic environment.


Asunto(s)
Células Artificiales , Humanos , Sustancias Macromoleculares
2.
Int Microbiol ; 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38206524

RESUMEN

Pseudomonas spp., such as P. fluorescens group, P. fragi, and P. putida, are the major psychrophilic spoilage bacteria in the food industry. Bacteriophages (phages) are a promising tool for controlling food-spoilage and food-poisoning bacteria; however, there are few reports on phages effective on food-spoilage bacteria such as Pseudomonas spp. In this study, 12 Pseudomonas phages were isolated from chicken and soil samples. Based on the host range and lytic activity at 30 °C and 4 °C and various combinations of phages, phages vB_PflP-PCS4 and vB_PflP-PCW2 were selected to prepare phage cocktails to control Pseudomonas spp. The phage cocktail consisting of vB_PflP-PCS4 and vB_PflP-PCW2 showed the strongest lytic activity and retarded regrowth of P. fluorescens and P. putida at 30 °C, 8 °C, and 4 °C at a multiplicity of infection of 100. Nucleotide sequence analysis of the genomic DNA indicated that vB_PflP-PCS4 and vB_PflP-PCW2 phages were lytic phages of the Podoviridae family and lacked tRNA, toxin, or virulence genes. A novel endolysin gene was found in the genomic DNA of phage vB_PflP-PCS4. The results of this study suggest that the phage cocktail consisting of vB_PflP-PCS4 and vB_PflP-PCW2 is a promising tool for the biocontrol of psychrophilic food-spoilage pseudomonads during cold storage and distribution.

3.
J Appl Microbiol ; 135(1)2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38142224

RESUMEN

AIMS: The study was to identify the genes involved in phage resistance and to develop an effective biocontrol method to improve the lytic activity of phages against foodborne pathogens. METHODS AND RESULTS: A total of 3,909 single gene-deletion mutants of Escherichia coli BW25113 from the Keio collection were individually screened for genes involved in phage resistance. Phage S127BCL3 isolated from chicken liver, infecting both E. coli BW25113 and O157: H7, was characterized and used for screening. The 10 gene-deletion mutants showed increased susceptibility to phage S127BCL3. Among them, priA gene-deletion mutant strain showed significant susceptibility to the phages S127BCL3 and T7. Furthermore, we investigated the substances that have been reported to inhibit the function of primosomal protein A (PriA) and were used to confirm increased phage susceptibility in E. coli BW25113 (Parent strain) and O157: H7. CONCLUSION: PriA inhibitors at a low concentration showed combined effects with phage against E. coli O157: H7 and delayed the regrowth rate of phage-resistant cells.


Asunto(s)
Bacteriófagos , Escherichia coli O157 , Proteínas de Escherichia coli , Bacteriófagos/genética , Proteína Estafilocócica A , ADN Helicasas , Proteínas de Escherichia coli/genética
4.
Int J Med Sci ; 21(5): 949-957, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38616998

RESUMEN

Background: Tonsillectomy is a common surgery in the US, with possible postoperative complications. While small studies indicate postoperative depressive symptoms may occur, large-scale evidence is lacking on the tonsillectomy-depression link. Methods: We conducted a retrospective cohort study using the TriNetX US collaborative network, offering de-identified electronic health data from 59 collaborative healthcare organizations (HCOs) in the United States. In this study, people being diagnosed of chronic tonsillitis between January 2005 and December 2017 were enrolled. Patients deceased, with previous record of cancers or psychiatric events before index date were excluded. 14,874 chronic tonsillitis patients undergoing tonsillectomy were propensity score matched 1:1 to controls for age, sex, and race. New-onset depression risks were evaluated over 5 years post-tonsillectomy and stratified by age and sex. Confounders were adjusted for including demographics, medications, comorbidities and socioeconomic statuses. Results: After matching, the difference of key baseline characteristics including age, sex, comedications status and obesity status was insignificant between tonsillectomy and non-tonsillectomy groups. Tonsillectomy had a 1.29 times higher 5-year depression risk versus matched controls (95% CI, 1.19-1.40), with elevated risks seen at 1 year (HR=1.51; 95% CI, 1.28-1.79) and 3 years (HR=1.30; 95% CI, 1.18-1.43). By stratifications, risks were increased for both males (HR=1.30; 95% CI, 1.08-1.57) and females (HR=1.30; 95% CI, 1.18-1.42), and significantly higher in ages 18-64 years (HR=1.37; 1.26-1.49), but no significance observed for those 65 years and older. After performing sensitivity analyses and applying washout periods of 6, 12, and 36 months, the outcome remained consistent with unadjusted results. Conclusion: This real-world analysis found tonsillectomy was associated with a 30% higher 5-year depression risk versus matched non-tonsillectomy patients with chronic tonsillitis. Further mechanistic research is needed to clarify the pathophysiologic association between depression and tonsillectomy. Depression is not commonly mentioned in the current post-tonsillectomy care realm; however, the outcome of our study emphasized the possibility of these suffering condition after operation. Attention to psychological impacts following tonsillectomy is warranted to support patient well-being, leading to better management of post-tonsillectomy individuals.


Asunto(s)
Depresión , Tonsilectomía , Femenino , Masculino , Humanos , Depresión/epidemiología , Depresión/etiología , Estudios Retrospectivos , Tonsilectomía/efectos adversos , Ansiedad , Enfermedad Crónica
5.
Int J Med Sci ; 21(2): 299-305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38169580

RESUMEN

Background: Cross-sectional evidence has suggested a high prevalence of atopic diseases in patients with hidradenitis suppurativa (HS). However, there is a lack of evidence based on longitudinal studies. This study aimed to assess the risk of different atopic diseases, including asthma, atopic dermatitis, and allergic rhinitis, in patients with HS. Methods: In this retrospective cohort study, data from the TriNetX research network were obtained. Patients with HS were enrolled, and a 1:1 propensity score matching was performed to select a non-HS control group. Matching covariates included age, sex, race, comorbidities, comedications, socioeconomic status, lab data, and medical utilization status. Hazard ratios (HR) for atopic diseases were assessed. Results: Over a 15-year follow-up period, patients with HS were found to be at a higher risk for atopic dermatitis (HR = 1.65; 95% CI, 1.44-1.90), asthma (HR = 1.41; 95% CI, 1.33-1.49), and allergic rhinitis (HR = 1.08; 95% CI, 1.03-1.13). A similar trend was observed in shorter follow-up periods. The association between HS, atopic dermatitis, and asthma was consistent across different age and sex subgroups. Conclusion: Atopic diseases including atopic dermatitis, asthma and allergic rhinitis are associated with HS. Further investigation is needed to assess the necessity of early screening for atopic diseases in patients with HS.


Asunto(s)
Asma , Dermatitis Atópica , Hidradenitis Supurativa , Rinitis Alérgica , Humanos , Dermatitis Atópica/complicaciones , Dermatitis Atópica/epidemiología , Estudios de Cohortes , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/epidemiología , Estudios Retrospectivos , Estudios Transversales , Puntaje de Propensión , Asma/epidemiología , Rinitis Alérgica/complicaciones , Rinitis Alérgica/epidemiología
6.
Int J Med Sci ; 21(5): 874-881, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617008

RESUMEN

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with systemic symptoms. Periodontitis, a prevalent dental disease, shares immune-mediated inflammatory characteristics with HS. This cohort study aims to evaluate the association between HS and periodontitis. Methods: Using the TriNetX research network, a global-federated database of electronic health records, we conducted a retrospective cohort study. People being diagnosed of HS were identified and propensity score matching was performed to identify proper control group, via balancing critical covariates Within the follow-up time of 1 year, 3 year and 5 years, hazard ratios were calculated to assess the risk of periodontitis in HS patients compared to controls. Results: Within the 53,968 HS patients and the same number of matched controls, the HS patients exhibited a significantly increased risk of developing periodontitis compared to controls after 3 years of follow-up (HR: 1.64, 95% CI: 1.11, 2.44) and 5 years of follow-up (HR: 1.64, 95% CI: 1.21, 2.24) of follow-up. Sensitivity analyses supported these findings under various matching models and washout periods. While comparing with patients with psoriasis, the association between HS and periodontitis remained significant (HR: 1.73, 95% CI: 1.23, 2.44). Conclusion: The observed increased risk suggests the need for heightened awareness and potential interdisciplinary care for individuals with HS to address periodontal health.


Asunto(s)
Hidradenitis Supurativa , Periodontitis , Humanos , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/epidemiología , Estudios de Cohortes , Puntaje de Propensión , Estudios Retrospectivos , Periodontitis/complicaciones , Periodontitis/epidemiología , Factores de Riesgo
7.
Nucleic Acids Res ; 50(12): 7048-7066, 2022 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-35736218

RESUMEN

DICER1 syndrome is a cancer pre-disposition disorder caused by mutations that disrupt the function of DICER1 in miRNA processing. Studying the molecular, cellular and oncogenic effects of these mutations can reveal novel mechanisms that control cell homeostasis and tumor biology. Here, we conduct the first analysis of pathogenic DICER1 syndrome allele from the DICER1 3'UTR. We find that the DICER1 syndrome allele, rs1252940486, abolishes interaction with the PUMILIO RNA binding protein with the DICER1 3'UTR, resulting in the degradation of the DICER1 mRNA by AUF1. This single mutational event leads to diminished DICER1 mRNA and protein levels, and widespread reprogramming of miRNA networks. The in-depth characterization of the rs1252940486 DICER1 allele, reveals important post-transcriptional regulatory events that control DICER1 levels.


Asunto(s)
MicroARNs , ARN Mensajero , MicroARNs/genética
8.
Cancer Invest ; : 1-10, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36657101

RESUMEN

MT-3724 is an engineered direct-kill immunotoxin comprised of a CD20-specific scFv fused to a Shiga-like toxin subunit. In this phase IIa study, eight patients with relapsed diffuse large B-cell lymphoma were treated with MT-3724 combined with gemcitabine and oxaliplatin (GEMOX). The objective response rate was 85.7%, with a median duration of response of 2.2 months. The 12-month overall survival and progression-free survival were 71.4% and 28.6%, respectively. Two patients experienced grade 2 capillary leak syndrome (CLS). Combination therapy with MT-3724 and GEMOX demonstrated an early efficacy signal but was limited by the incidence of CLS.

9.
BMC Ophthalmol ; 23(1): 360, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37596535

RESUMEN

BACKGROUND: To report a case of simultaneous occurrence of acute exacerbation of ocular graft-versus-host disease (GVHD) and anterior uveitis following coronavirus disease 2019 (COVID-19) vaccination. CASE PRESENTATION: A 60-year-old man with primary myelofibrosis and GVHD after receiving allogeneic hematopoietic stem cell transplantation (HSCT), developed acute exacerbation of ocular GVHD and anterior uveitis after receiving first dose of COVID-19 vaccine. The patient developed erythema of the eyelids, conjunctival hyperemia, superficial punctate keratopathy, and prominent anterior chamber inflammation in both eyes. The ocular GVHD and anterior uveitis were managed with mainly topical corticosteroids, antibiotics, lubricants, and systemic corticosteroids, but were difficult to control. Intravitreal injection of dexamethasone was administered, and the inflammation gradually subsided 6 months after the onset of initial symptoms. CONCLUSIONS: Clinicians should be aware of rare refractory anterior uveitis and acute exacerbation of ocular GVHD after COVID-19 vaccination in patients undergoing HSCT. Early diagnosis and aggressive treatment should be considered to reduce the likelihood of severe complications.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Enfermedad Injerto contra Huésped , Uveítis Anterior , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Aguda , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Párpados , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Inflamación , Uveítis Anterior/diagnóstico , Uveítis Anterior/etiología
10.
Int J Mol Sci ; 24(16)2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37629106

RESUMEN

The plant-specific RWP-RK transcription factor family plays a central role in the regulation of nitrogen response and gametophyte development. However, little information is available regarding the evolutionary relationships and characteristics of the RWP-RK family genes in cassava, an important tropical crop. Herein, 13 RWP-RK proteins identified in cassava were unevenly distributed across 9 of the 18 chromosomes (Chr), and these proteins were divided into two clusters based on their phylogenetic distance. The NLP subfamily contained seven cassava proteins including GAF, RWP-RK, and PB1 domains; the RKD subfamily contained six cassava proteins including the RWP-RK domain. Genes of the NLP subfamily had a longer sequence and more introns than the RKD subfamily. A large number of hormone- and stress-related cis-acting elements were found in the analysis of RWP-RK promoters. Real-time quantitative PCR revealed that all MeNLP1-7 and MeRKD1/3/5 genes responded to different abiotic stressors (water deficit, cold temperature, mannitol, polyethylene glycol, NaCl, and H2O2), hormonal treatments (abscisic acid and methyl jasmonate), and nitrogen starvation. MeNLP3/4/5/6/7 and MeRKD3/5, which can quickly and efficiently respond to different stresses, were found to be important candidate genes for further functional assays in cassava. The MeRKD5 and MeNLP6 proteins were localized to the cell nucleus in tobacco leaf. Five and one candidate proteins interacting with MeRKD5 and MeNLP6, respectively, were screened from the cassava nitrogen starvation library, including agamous-like mads-box protein AGL14, metallothionein 2, Zine finger FYVE domain containing protein, glyceraldehyde-3-phosphate dehydrogenase, E3 Ubiquitin-protein ligase HUWE1, and PPR repeat family protein. These results provided a solid basis to understand abiotic stress responses and signal transduction mediated by RWP-RK genes in cassava.


Asunto(s)
Manihot , Manihot/genética , Peróxido de Hidrógeno , Filogenia , Verduras , Biblioteca de Genes
11.
J Immunol ; 205(10): 2694-2706, 2020 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-33077646

RESUMEN

Myeloid phagocytes, neutrophils in particular, are easily consumed when they fight against a large number of invading microbes. Hence, they require efficient and constant replenishment from their progenitors via the well-orchestrated emergency myelopoiesis in the hematopoietic organs. The cellular and molecular details of the danger-sensing and warning processes to activate the emergency myelopoiesis are still under debate. In this study, we set up a systemic infection model in zebrafish (Danio rerio) larvae via circulative administration of LPS. We focused on the cross-talk of macrophages with myeloid progenitors in the caudal hematopoietic tissue. We revealed that macrophages first detected LPS and sent out the emergency message via il1ß The myeloid progenitors, rather than hematopoietic stem and progenitor cells, responded and fulfilled the demand to adapt myeloid expansion through the synergistic cooperation of NF-κB and C/ebpß. Our study unveiled a critical role of macrophages as the early "whistle blowers" to initiate emergency myelopoiesis.


Asunto(s)
Infecciones Bacterianas/inmunología , Interleucina-1beta/metabolismo , Mielopoyesis/inmunología , Proteínas de Pez Cebra/metabolismo , Animales , Animales Modificados Genéticamente , Proteína beta Potenciadora de Unión a CCAAT/genética , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Modelos Animales de Enfermedad , Embrión no Mamífero , Humanos , Interleucina-1beta/genética , Lipopolisacáridos/inmunología , Macrófagos/enzimología , Macrófagos/metabolismo , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Pez Cebra , Proteínas de Pez Cebra/genética
12.
Int J Mol Sci ; 24(1)2022 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-36613644

RESUMEN

Numerous recent advancements in T-cell based immunotherapies have revolutionized the treatment of hematologic malignancies. In the race towards the first approved allogeneic cellular therapy product, there is growing interest in utilizing natural killer (NK) cells as a platform for off-the-shelf cellular therapies due to their scalable manufacturing potential, potent anti-tumor efficacy, and superior safety profile. Allogeneic NK cell therapies are now being actively explored in the setting of hematopoietic stem cell transplantation and adoptive transfer. Increasingly sophisticated gene editing techniques have permitted the engineering of chimeric antigen receptors, ectopic cytokine expression, and tumor recognition signals to improve the overall cytotoxicity of NK cell therapies. Furthermore, the enhancement of antibody-dependent cellular cytotoxicity has been achieved through the use of NK cell engagers and combination regimens with monoclonal antibodies that act synergistically with CD16-expressing NK cells. Finally, a greater understanding of NK cell biology and the mechanisms of resistance have allowed the preclinical development of NK checkpoint blockade and methods to modulate the tumor microenvironment, which have been evaluated in early phase trials. This review will discuss the recent clinical advancements in NK cell therapies in hematologic malignancies as well as promising avenues of future research.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Humanos , Células Asesinas Naturales , Neoplasias/metabolismo , Inmunoterapia Adoptiva/métodos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/metabolismo , Inmunidad Innata , Microambiente Tumoral
13.
Int J Mol Sci ; 23(21)2022 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-36362179

RESUMEN

Low-intensity pulsed ultrasound (LIPUS), a therapeutic type of ultrasound, is known to enhance bone fracture repair processes and help some tissues to heal. Here, we investigated the therapeutic potential of LIPUS for the treatment of chronic kidney disease (CKD) in two CKD mouse models. CKD mice were induced using both unilateral renal ischemia/reperfusion injury (IRI) with nephrectomy and adenine administration. The left kidneys of the CKD mice were treated using LIPUS with the parameters of 3 MHz, 100 mW/cm2, and 20 min/day, based on the preliminary experiments. The mice were euthanized 14 days after IRI or 28 days after the end of adenine administration. LIPUS treatment effectively alleviated the decreases in the body weight and albumin/globulin ratio and the increases in the serum renal functional markers, fibroblast growth factor-23, renal pathological changes, and renal fibrosis in the CKD mice. The parameters for epithelial-mesenchymal transition (EMT), senescence-related signal induction, and the inhibition of α-Klotho and endogenous antioxidant enzyme protein expression in the kidneys of the CKD mice were also significantly alleviated by LIPUS. These results suggest that LIPUS treatment reduces CKD progression through the inhibition of EMT and senescence-related signals. The application of LIPUS may be an alternative non-invasive therapeutic intervention for CKD therapy.


Asunto(s)
Transición Epitelial-Mesenquimal , Insuficiencia Renal Crónica , Ratones , Animales , Riñón/metabolismo , Insuficiencia Renal Crónica/metabolismo , Fibrosis , Biomarcadores/metabolismo , Adenina/metabolismo
14.
J Cell Physiol ; 236(9): 6481-6495, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33580514

RESUMEN

AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45+ intratumoral infiltrating lymphocytes (TILs) and memory CD45RO+ TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , Estrés del Retículo Endoplásmico , Proteínas de Choque Térmico/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Anciano , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Femenino , Homeostasis/efectos de los fármacos , Humanos , Muerte Celular Inmunogénica/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Ratones Endogámicos BALB C , Modelos Biológicos , Análisis Multivariante , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Unión Proteica/efectos de los fármacos , Estabilidad Proteica/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología
15.
Breast Cancer Res Treat ; 187(2): 397-405, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34076801

RESUMEN

BACKGROUND: Clinical and genomic data from patients with early-stage breast cancer suggest more aggressive disease in premenopausal women. However, the association between age, disease course, and molecular profile from liquid biopsy in metastatic breast cancer (MBC) is not well characterized. METHODS: Patients were classified as premenopausal (< 45 years), perimenopausal (45-55 years), or postmenopausal (> 55 years). Cohort 1 consisted of patients with MBC who consented for prospective serial evaluation of circulating tumor cells (CTCs) using CellSearch™. Cohort 2 included patients who, as part of routine care, had circulating tumor DNA (ctDNA) sequenced by the Guardant360™ assay. Clinicopathologic data were collected from retrospective review to compare disease features between premenopausal and postmenopausal women. RESULTS: Premenopausal women represented 26% of 138 patients in Cohort 1 and 21% of 253 patients in Cohort 2. In Cohort 1, younger patients had a shorter time to metastases and a higher prevalence of lung and brain metastases. Overall, there were similar rates of ≥ 5 CTCs/7.5 mL, HER2 + CTC expression, and CTC clusters between pre- and postmenopausal women. However, for those with triple negative breast cancer, premenopausal women had a higher proportion of ≥ 5 CTCs/7.5 mL. In Cohort 2, premenopausal women had a higher incidence of FGFR1 (OR 2.75, p = 0.022) and CCND2 (OR 6.91, p = 0.024) alterations. There was no difference in the ctDNA mutant allele frequency or the number of detected alterations between these age groups. CONCLUSIONS: Our data reveal that premenopausal women diagnosed with MBC have unique clinical, pathologic, and molecular features when compared to their postmenopausal counterparts. Our results highlight FGFR1 inhibitors as potential therapeutics of particular interest among premenopausal women.


Asunto(s)
Neoplasias de la Mama , ADN Tumoral Circulante , Células Neoplásicas Circulantes , Biomarcadores de Tumor/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , ADN Tumoral Circulante/genética , Femenino , Humanos , Biopsia Líquida , Estudios Prospectivos , Estudios Retrospectivos
16.
Small ; 17(23): e2101162, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33977654

RESUMEN

The development of synthetic systems that enable the sustained active self-assembly of molecular blocks to mimic the complexity and dynamic behavior of living systems is of great interest in elucidating the origins of life, understanding the basic principles behind biological organization, and designing active materials. However, it remains a challenge to construct microsystems with dynamic behaviors and functions that are connected to molecular self-assembly processes driven by external energy. Here, an active self-assembly of microdroplet protocells with dynamic structure and high structural complexity through living radical polymerization under constant energy flux is reported. The active microdroplet protocells exhibit nonlinear behaviors including oscillatory growth and shrinkage. This relies on the transient stabilization of molecular assembly, which can channel the inflow of energy through noncovalent interactions of pure synthetic components. The intercommunication of microdroplet protocells through stochastic fusion leads to the formation of a variety of dynamic and higher-order biomimetic microstructures. This work constitutes an important step toward the realization of autonomous and dynamic microsystems and active materials with life-like properties.


Asunto(s)
Células Artificiales , Biomimética , Polimerizacion
17.
Cancer Invest ; 39(10): 871-879, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34643126

RESUMEN

Novel therapeutics are needed for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Everolimus is an mTOR pathway inhibitor with synergistic anti-tumor activity when combined with histone deacetylase inhibitors, such as panobinostat, in preclinical lymphoma models. In this Phase II study, we evaluated overall response rate to single and combination everolimus and panobinostat in R/R DLBCL. Fifteen patients were enrolled to single-agent and 18 to combination. One patient responded to everolimus, while none responded to panobinostat. Though 25% of patients responded to combination therapy, responses were not durable with significant toxicity. We demonstrated minimal single-agent activity and prohibitive toxicity with combination therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Everolimus/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Panobinostat/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Everolimus/administración & dosificación , Everolimus/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Panobinostat/administración & dosificación , Panobinostat/efectos adversos , Estudios Prospectivos , Recurrencia
18.
Nucleic Acids Res ; 47(11): 5490-5501, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-31076772

RESUMEN

RNA is an essential player in almost all biological processes, and has an ever-growing number of roles in regulating cellular growth and organization. RNA functions extend far beyond just coding for proteins and RNA has been shown to function in signaling events, chromatin organization and transcriptional regulation. Dissecting how the complex network of RNA-binding proteins (RBPs) and regulatory RNAs interact with their substrates within the cell is a real, but exciting, challenge for the RNA community. Investigating these biological questions has fueled the development of new quantitative technologies to measure how RNA and RBPs interact both locally and on a global scale. In this review, we provide an assessment of available approaches to enable researchers to select the protocol most applicable for their experimental question.


Asunto(s)
Proteínas de Unión al ARN/genética , ARN/genética , Sitios de Unión , Reactivos de Enlaces Cruzados , Regulación de la Expresión Génica , Procesos Fotoquímicos/efectos de la radiación , Dominios Proteicos , ARN/metabolismo , Proteínas de Unión al ARN/metabolismo , Rayos Ultravioleta
19.
Nanomedicine ; 33: 102348, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33321215

RESUMEN

Atherosclerosis can lead to most cardiovascular diseases. Although some biomimetic nanomaterials coated by macrophage membranes have been reported in previous studies of atherosclerosis, to our knowledge, no studies regarding the detection of early lesions of atherosclerosis (foam cells) using such a strategy have yet been reported. In the present study, Fe3O4 biomimetic nanoparticles coated with a macrophage membrane (Fe3O4@M) were prepared to investigate the imaging effect on the early lesions of atherosclerosis (foam cells). The results showed that the Fe3O4@M particles are spheres with average diameters of approximately 300 nm. T1 and T2 relaxation values showed that the ratio of r2 to r1 was 26.09. The protein content accounted for approximately 27% of the total weight in Fe3O4@M, and Fe3O4@M nanoparticles exhibited high biosafety. Further testing showed that Fe3O4@M effectively targets early atherosclerotic lesions by the specific recognition of integrin α4ß1 to VCAM-1. Taken together, Fe3O4@M is a promising contrast agent for the diagnosis of early stage atherosclerosis.


Asunto(s)
Materiales Biomiméticos/química , Medios de Contraste/química , Nanopartículas de Magnetita/química , Animales , Aterosclerosis , Permeabilidad de la Membrana Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Macrófagos/química , Macrófagos/metabolismo , Imagen por Resonancia Magnética , Ratones , Células RAW 264.7 , Propiedades de Superficie , Molécula 1 de Adhesión Celular Vascular/metabolismo
20.
Hu Li Za Zhi ; 68(1): 54-63, 2021 Feb.
Artículo en Zh | MEDLINE | ID: mdl-33521919

RESUMEN

BACKGROUND: Failure to follow the "Five Rights" and interruptions during medication administration are the two most common factors underlying nurse-related medication errors. PURPOSE: This study was designed to examine the effectiveness in terms of improving nurses' medication administration self-efficacy and recognition of medication errors of an online objective structured video examination (OSVE) intervention focused on the "Five Rights" and "management of interruptions during medication administration". METHODS: A quasi-experimental pretest-posttest research design with a respondent-driven sampling method was employed. One hundred and twelve nurses finished the online survey. Instruments included the self-efficacy of medication administration questionnaire and four online medication error OSVEs addressing the issue of medication error recognition. The intervention was an acute medication behavior OSVE. Paired t-tests were used to assess the pre-test / post-test differences between variables. RESULTS: The mean age of the 112 survey respondents was 27.21 years, and the mean years of working experience was 4.67. The mean self-efficacy of medication administration score, which was 38.88 (SD = 4.45) at baseline, increased significantly to 41.69 (SD = 4.58) at post-test (t = 7.11, p < .001). Similarly, the mean score for recognition of medication errors was 10.71 (SD = 7.16) at pre-test and significantly higher (15.32; SD = 4.94) at post-test (t = 5.90, p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The online OSVE may be used to improve the recognition of medication errors and self-efficacy of medication administration in nurses. Future research is needed to examine the effect of this intervention in enhancing the safety of medication administration in actual clinical practice settings.


Asunto(s)
Errores de Medicación , Autoeficacia , Adulto , Humanos , Enfermeras y Enfermeros , Encuestas y Cuestionarios
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