NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment.

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

Stimulated thyroglobulin and pre-ablation antithyroglobulin antibody products can predict the response to radioiodine therapy of TgAb-positive differentiated thyroid cancer patients: a retrospective study.

Objective: We aimed to explore the predictive value of stimulated thyroglobulin (sTg) and pre-ablation antithyroglobulin (pa-TgAb) products for the effect of radioiodine therapy (RAIT) on TgAb-positive differentiated thyroid cancer (DTC) patients. Methods: In this study, we enrolled 265 patients with TgAb-positive DTC who underwent RAIT after total thyroidectomy (TT). Based on the last follow-up result, the patients were divided into two groups: the excellent response (ER) group and the non-excellent response (NER) group. We analyzed the factors related to the effect of RAIT. Results: The ER group consisted of 197 patients. The NER group consisted of 68 patients. For the univariate analysis, we found that the maximal tumor diameter, whether with extrathyroidal extension (ETE), bilateral or unilateral primary lesion, multifocality, preoperative TgAb (preop-TgAb), pa-TgAb, sTg × pa-TgAb, initial RAIT dose, N stage, and surgical extent (modified radical neck dissection or not), showed significant differences between the ER group and NER group (all p-values <0.05). The receiver operating characteristic (ROC) curves showed that the cutoff value was 724.25 IU/ml, 424.00 IU/ml, and 59.73 for preop-TgAb, pa-TgAb, and sTg × pa-TgAb, respectively. The multivariate logistic regression analysis results indicated that pa-TgAb, sTg × pa-TgAb, initial RAIT dose, and N stage were independent risk factors for NER (all p-values <0.05). For the Kaplan-Meier analysis of disease-free survival (DFS), the median DFS of the patients with sTg × pa-TgAb < 59.73 and initial RAIT dose ≤ 100 mCi was significantly longer than that of the patients with sTg × pa-TgAb ≥ 59.73 (50.27 months vs. 48.59 months, p = 0.041) and initial RAIT dose >100 mCi (50.50 months vs. 38.00 months, p = 0.030). Conclusion: We found the sTg and pa-TgAb conducts is a good predictor of the efficacy of RAIT in TgAb-positive DTC patients. It can play a very positive and important role in optimizing treatment, improving prognosis, and reducing the burden of patients.

Modificaciones biométricas en paciente miopes con implante de la lente fáquica ACRIOL 128

Objetivo: Determinar las modificaciones biométricas en pacientes miopes con implante de la lente fáquica ACRIOL 128. Métodos: Se realizó un estudio transversal con 31 ojos (17 pacientes) con alta miopía tratados con implante de lente fáquica ACRIOL 128, entre septiembre 2016 y febrero 2019, los cuales tenían mediciones biométricas preoperatorias con el sistema IOL Master 3.0.2 y estabilidad refractiva posoperatoria (≤ 0,5 dioptrías) después de los tres meses del implante. Se les efectuaron las mediciones posoperatorias con el propio IOL Master 3.0.2 en modo lente fáquica y con el sistema Scheimpflug Pentacam AXL para compararlas, mediante la prueba t para datos pareados, con una significación del 95 %. Resultados: La edad promedio fue de 29,82 ± 5,99 años, el 82,4 % del sexo femenino. El equivalente esférico preoperatorio medio fue de -12,00 ± 4,10 dioptrías. La diferencia de longitud axial y profundidad de la cámara anterior en milímetros entre el pre- y posoperatorio fue significativa con IOL Master 3.0.2 (0,13 ± 0,33 y -0,08 ± 0,17) y Pentacam AXL (0,12 ± 0,32 y -0,10 ± 0,24), respectivamente. Sin embargo, las posoperatorias entre ambos equipos no fueron significativas (p>0,05) para estas variables, pero sí para las queratometrías. Conclusiones: El implante de la lente fáquica ACRIOL 128 modifica la medición de la longitud axial y la profundidad de la cámara anterior. El IOL Master 3.0.2 y el Pentacam AXL ofrecen mediciones de longitud axial y profundidad de cámara anterior posoperatorias similares, no así para las queratometrías.

Objective: To determine the biometric modifications in myopic patients with ACRIOL 128 phakic lens implantation. Methods: A cross-sectional study was performed on 31 eyes (17 patients) with high myopia treated with ACRIOL 128 phakic lens implant, between September 2016 and February 2019, which had preoperative biometric measurements with the IOL Master 3.0.2 system and postoperative refractive stability (≤ 0.5 diopters) after three months of implantation. Postoperative measurements were performed with the IOL Master 3.0.2 in phakic lens mode and with the Scheimpflug Pentacam AXL system for comparison, using the t-test for paired data, with 95% significance. Results: The average age was 29.82 ± 5.99 years, 82.4% female. The mean preoperative spherical equivalent was -12.00 ± 4.10 diopters. The difference in axial length and anterior chamber depth in millimeters between pre- and postoperative was significant with IOL Master 3.0.2 (0.13 ± 0,33 and -0.08 ± 0.17) and Pentacam AXL (0.12 ± 0.32 and -0.10 ± 0.24), respectively. However, postoperative between the two teams were not significant (p > 0.05) for these variables but significant for keratometries. Conclusions: Implantation of the ACRIOL 128 phakic lens modifies the measurement of axial length and anterior chamber depth. The IOL Master 3.0.2 and Pentacam AXL provide similar postoperative axial length and anterior chamber depth measurements, but not for keratometries.

FAM3D: A gut secreted protein and its potential in the regulation of glucose metabolism.

The number of diabetic patients is rising globally and concomitantly so do the diabetes associated complications. The gut secretes a variety of proteins to control blood glucose levels and/or food intake. As the drug class of GLP-1 agonists is based on a gut secreted peptide and the positive metabolic effects of bariatric surgery are at least partially mediated by gut peptides, we were interested in other gut secreted proteins which have yet to be explored. In this respect we identified the gut secreted protein FAM3D by analyzing sequencing data from L- and epithelial cells of VSG and sham operated as well as chow and HFD fed mice. FAM3D was overexpressed in diet induced obese mice via an adeno-associated virus (AAV), which resulted in a significant improvement of fasting blood glucose levels, glucose tolerance and insulin sensitivity. The liver lipid deposition was reduced, and the steatosis morphology was improved. Hyperinsulinemic clamps indicated that FAM3D is a global insulin sensitizer and increases glucose uptake into various tissues. In conclusion, the current study demonstrated that FAM3D controls blood glucose levels by acting as an insulin sensitizing protein and improves hepatic lipid deposition.

Perspectiva social del impacto de la miopía / Social perspective of the impact of myopia

La visión, el más dominante de los sentidos, tiene un papel esencial en cada aspecto y etapa de la vida. Se da por sentada la visión, pero sin ella, resulta difícil la realización de tareas cotidianas como aprender a caminar, leer, conducir y trabajar. La miopía es una alteración visual que se encuentra entre las cinco condiciones, donde su atención clínica ha sido calificada de prioridad inmediata para la Organización Mundial de la Salud. La prevalencia de la miopía y la miopía magna aumentan a nivel mundial a un ritmo alarmante. Existen diversos factores socioeconómicos, psicológicos y sociales que impactan en la calidad de vida de quienes la padecen. De ahí la motivación de realizar un acercamiento a dichas variables para comprender desde una perspectiva social las implicaciones de esta afección visual mediante una búsqueda actualizada de diversos artículos publicados, con el objetivo de identificar los problemas sociales relacionados a la miopía. Se utilizó la plataforma Infomed, específicamente la Biblioteca Virtual de Salud, con todos sus buscadores(AU)

The vision, the dominantest in the senses, has an essential paper in each aspect and stage of the life. It is given by sitting the vision, but without her, it is difficult the realization of daily tasks as learning how to walk, to read, to drive and to work. The myopia is a visual alteration that is between the five conditions where its clinical attention it has been described as immediate priority for the World Organization of the Health. The prevalencia of the myopia and the great myopia increase at world level to an alarming rhythm. Diverse socioeconomic, psychological and social factors that impact in the quality of life of who you/they suffer it, exist of there the motivation of carrying out an approach to this variables to understand from a social perspective the implications of this visual affection by means of a modernized search of diverse published articles, with the objective of identifying the social problems related to the myopia. The platform Infomed was used, specifically the Virtual Library of Health, with all its searchers(AU)

Efficacy evaluation and influencing factor analysis of postoperative 131I for the treatment of primary hyperthyroidism combined with differentiated thyroid cancer (DTC)-a retrospective cohort study.

Background: 131I treatment is one of the important methods of comprehensive postoperative treatment for patients with hyperthyroidism complicated with differentiated thyroid cancer (DTC). Early identification of patients with poor treatment efficacy of 131I is particularly important. Current studies mainly focus on the relationship between hyperthyroidism and the occurrence and development of DTC, and there are few studies on the factors affecting the curative effect. The purpose of this study was to find the influencing factors of efficacy evaluation and provide evidence for early identification of patients with poor efficacy in DTC combined with primary hyperthyroidism patients. Methods: This was a retrospective analysis of DTC patients with primary hyperthyroidism who received 131I treatment in our department from 2012 to 2021. Follow-up intervals were 3 months within 1 year, 6 months within 1 to 2 years, and annual follow-up thereafter, the median follow-up time was 12.0 (3.0, 24.0) months. Serological examination and imaging examination were used to evaluate the efficacy. Patients were classified into an excellent response (ER) group and a non-ER group based on treatment response more than 6 months after 131I treatment. Univariate analysis and multivariate logistic regression analysis were performed on the basic clinical characteristics, pathological characteristics and curative effect of the patients, in order to find independent risk factors affecting the curative effect. Results: Eighty-nine patients were mostly female (80.9%), the average age was 43.47±11.88 years old, and tumor size was 1.2 (0.75, 1.80) cm, 56 patients (62.9%) in the ER group. psTg [odds ratio (OR): 1.325; 95% confidence interval (CI): 1.135-1.547; P<0.001], maximum tumor diameter (OR: 2.428; 95% CI: 1.392-4.235; P=0.002) and pathology-confirmed combined HT (OR: 8.669; 95% CI: 1.877-40.038; P=0.006) were independent risk factors for predicting ER. Conclusions: Our findings demonstrate that most hyperthyroidism combined with DTC patients could get favorable clinical outcomes from 131I treatment. The tumor diameter, pathology-confirmed diagnosis of combined HT, and psTg level can be used to identify patients who can get ER by the effect of 131I in hyperthyroidism combined with DTC at an early stage.

The influence of stimulated thyroglobulin and lymphocyte subsets before radioiodine therapy on the therapeutic response in patients with intermediate- and high-risk papillary thyroid carcinoma.

The aim of the present study was to investigate the factors influencing the short-term response to the initial radioiodine therapy (RT) course in patients with intermediate- and high-risk papillary thyroid carcinoma (PTC). A total of 182 patients with intermediate- and high-risk PTC who underwent RT in our hospital from March 2018 to October 2020 were retrospectively enrolled. The patients were divided into incomplete response (IR) and nonincomplete response (Non-IR) groups according to the response observed in clinical follow-up within 6-12 months after RT. Univariate and multivariate logistic regression analyses were used to investigate the effects of 15 observed factors on the response to RT. Receiver operating characteristic (ROC) curve analysis was used to determine the value of factors found to be significant in multivariate analyses for predicting an IR. A total of 182 patients with intermediate- and high-risk PTC were analyzed; the percentage of patients with a Non-IR was 61.54% (112/182), and the percentage of patients with an IR was 38.46% (70/182). The CD4+ T-cell percentage (t = 4.757, P = 0.000), CD4/CD8 (z = - 2.632, P = 0.008), stimulated thyroglobulin (sTg) level (z = - 8.273, P = 0.000) and M stage (χ2 = 17.823, P = 0.000) of the two groups were significantly different. Multivariate analysis showed that only the sTg level (OR: 1.116, 95% CI 1.068-1.165, P < 0.001) and CD4+ T-cell percentage (OR: 0.909, 95% CI 0.854-0.968, P = 0.003) were independent factors associated with the therapeutic response to RT. The cutoff sTg level and CD4+ T-cell percentage for predicting an IR were 7.62 µg/L and 40.95%, respectively. The sTg level and CD4+ T-cell percentage were verified to be independent predictive factors of RT response. Higher sTg levels and lower CD4+ T-cell percentages were related to an IR in patients with intermediate- and high-risk PTC.

Current Progress of CAR-NK Therapy in Cancer Treatment.

CD8+ T cells and natural killer (NK) cells eliminate target cells through the release of lytic granules and Fas ligand (FasL)-induced target cell apoptosis. The introduction of chimeric antigen receptor (CAR) makes these two types of cells selective and effective in killing cancer cells. The success of CAR-T therapy in the treatment of acute lymphoblastic leukemia (ALL) and other types of blood cancers proved that the immunotherapy is an effective approach in fighting against cancers, yet adverse effects, such as graft versus host disease (GvHD) and cytokine release syndrome (CRS), cannot be ignored for the CAR-T therapy. CAR-NK therapy, then, has its advantage in lacking these adverse effects and works as effective as CAR-T in terms of killing. Despite these, NK cells are known to be hard to transduce, expand in vitro, and sustain shorter in vivo comparing to infiltrated T cells. Moreover, CAR-NK therapy faces challenges as CAR-T therapy does, e.g., the time, the cost, and the potential biohazard due to the use of animal-derived products. Thus, enormous efforts are needed to develop safe, effective, and large-scalable protocols for obtaining CAR-NK cells. Here, we reviewed current progress of CAR-NK therapy, including its biological properties, CAR compositions, preparation of CAR-NK cells, and clinical progresses. We also discussed safety issues raised from genetic engineering. We hope this review is instructive to the research community and a broad range of readers.

Gene therapy of Csf2ra deficiency in mouse fetal monocyte precursors restores alveolar macrophage development and function.

Tissue-resident macrophage-based immune therapies have been proposed for various diseases. However, generation of sufficient numbers that possess tissue-specific functions remains a major handicap. Here, we showed that fetal liver monocytes cultured with GM-CSF (CSF2-cFLiMo) rapidly differentiated into a long-lived, homogeneous alveolar macrophage-like population in vitro. CSF2-cFLiMo retained the capacity to develop into bona fide alveolar macrophages upon transfer into Csf2ra-/- neonates and prevented development of alveolar proteinosis and accumulation of apoptotic cells for at least 1 year in vivo. CSF2-cFLiMo more efficiently engrafted empty alveolar macrophage niches in the lung and protected mice from severe pathology induced by respiratory viral infection compared with transplantation of macrophages derived from BM cells cultured with M-CSF (CSF1-cBMM) in the presence or absence of GM-CSF. Harnessing the potential of this approach for gene therapy, we restored a disrupted Csf2ra gene in fetal liver monocytes and demonstrated their capacity to develop into alveolar macrophages in vivo. Altogether, we provide a platform for generation of immature alveolar macrophage-like precursors amenable for genetic manipulation, which will be useful to dissect alveolar macrophage development and function and for pulmonary transplantation therapy.

Seguridad del implante de lente fáquica ACR-128 tras un año de seguimiento / Safety of an ACR-128 phakic lens implant after one year's follow-up

Objetivo: Determinar la seguridad de los lentes fáquicos ACR-128 en la corrección de la alta miopía tras un año de implantados. Método: Se realizó un estudio transversal en 67 ojos de 36 pacientes con miopía corregida con lente fáquica ACR-128 (31 con ambos ojos y 5 con un solo ojo). Se determinó preoperatorio y posoperatorio: tensión ocular, pérdida celular endotelial según conteo, coeficiente de variación celular y hexagonalidad. Además de complicaciones posoperatorias y posición del lente respecto a endotelio y cristalino. El análisis estadístico se realizó con la prueba T para datos pareados, con una significación del 95 por ciento. Resultados: Edad media 28,06 ± 6,14 (25 mujeres y 11 hombres). Las complicaciones inmediatas fueron hipotonía OD: 1 (3,03 por ciento), OI: 1 (2,94 por ciento). La irregularidad de la pupila se presentó OD: 1 (3,03 por ciento), OI: 1 (2,94 por ciento) mediata y OD: 1 (3,03 por ciento), OI: 2 (5.88 por ciento) tardía. Tensión ocular promedio total preoperatorio 14,09 ± 2,51 y posoperatorio 14,22 ± 2,64 (p = 0,90). El conteo celular preoperatorio 2667,27 ± 228,72 y posoperatorio 2591,96 ± 301,21, con 2,94 por ciento pérdida endotelial total 75,31 ± 237,41 (p = 0,06). No hubo diferencias en el coeficiente de variación (p = 0,60) ni la hexagonalidad (p = 0,57). Posición del lente respecto al endotelio 2,09 mm y al cristalino 1,08 mm. Conclusiones: El implante de lente fáquica ACR-128 en la corrección de la alta miopía es un tratamiento seguro al no existir complicaciones posquirúrgico ni modificaciones en la tensión ocular y en el endotelio corneal tras un año del implante(AU)

Objective: Determine the safety of ACR-128 phakic lenses for high myopia correction one year after implantation. Method: A cross-sectional study was conducted of 67 eyes of 36 patients with myopia corrected with ACR-128 phakic lens implants (31 in both eyes and 5 in one eye). Pre- and postoperative determination was made of ocular tension, endothelial cell loss by count, cell variation coefficient and hexagonality, as well as of postoperative complications and lens position with respect to the endothelium and the crystalline lens. Statistical analysis was based on the paired T-test with a significance level of 95 percent Results: Mean age was 28.06 ± 6.14 (25 women and 11 men). An immediate complication was hypotonia: RE: 1 (3.03 percent), LE: 1 (2.94 percent). Pupil irregularity was mediate: RE: 1 (3.03 percent), LE: 1 (2.94 percent) and late: RE: 1 (3.03 percent), LE: 2 (5.88 percent). Total average ocular tension was 14.09 ± 2.51 preoperative and 14.22 ± 2.64 postoperative (p = 0.90). Cell count was 2667.27 ± 228.72 preoperative and 2591.96 ± 301.21 postoperative, with 2.94 percent total endothelial loss 75.31 ± 237.41 (p = 0.06). Differences were not found in the variation coefficient (p = 0.60) or in hexagonality (p = 0.57). Lens position was 2.09 mm with respect to the endothelium and 1.08 mm with respect to the crystalline lens. Conclusions: ACR-128 phakic lens implantation for high myopia correction is a safe procedure with no postoperative complications or modifications in ocular tension or the corneal endothelium after one year's follow-up(AU)

Calidad de vida relativa a la función visual en pacientes con implante de lente intraocular fáquico ACR-128 / Vision-related quality of life in patients undergoing ACR-128 phakic intraocular lens implantation

Introducción: El implante de una lente intraocular fáquico para corregir defectos de la refracción presenta una serie de ventajas respecto a otras técnicas como la cirugía refractiva corneal o la extracción de cristalino transparente. Objetivo: Describir los cambios en la calidad de vida relacionados con la función visual en la corrección de alta miopía con implante de lente fáquico ACR-128. Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo con análisis estadístico separado por ojos. La muestra total se correspondió con 91 ojos (46 derechos y 45 izquierdos) de 49 pacientes a los que se les implantó lente fáquico ACR-128 para la corrección de miopía. Mediante el test de Pelli-Robson se determinó la sensibilidad al contraste binocular a varias frecuencias espaciales y se les aplicó el cuestionario NEI-VFQ-25 antes de la cirugía (pretest) y a los tres meses de realizada la misma (postest). El análisis estadístico se realizó con la prueba T para datos pareados, con una significación del 95 por ciento. Resultados: Edad media 28,73 ± 5,85 años. Predominio del sexo femenino (71,43 por ciento). Hubo diferencias significativas en todas las frecuencias espaciales de la sensibilidad al contraste binocular entre el pre- y posoperatorio (p < 0,01). Al comparar el pretest y el postest (valoración retrospectiva de la calidad de vida prequirúrgica) no se encontraron diferencias significativas, lo que indicó que no hubo recalibración y que las diferencias con el postest que fueron significativas corroboren el verdadero cambio en la calidad de vida de estos pacientes tras la cirugía. Conclusiones: El implante de lentes fáquicos ACR-128 para la corrección de la alta miopía mejora la calidad de vida relacionada con la función visual sin cambios en su percepción antes y después de la cirugía(AU)

Introduction: Phakic intraocular lens implantation to correct refraction defects has a number of advantages with respect to techniques such as corneal refractive surgery or clear lens extraction. Objective: Describe the changes in vision-related quality of life resulting from high myopia correction by ACR-128 phakic lens implantation. Methods: A prospective longitudinal descriptive study was conducted with independent statistical analysis for each eye. The total sample was 91 eyes (46 right and 45 left) of 49 patients undergoing ACR-128 phakic lens implantation for myopia correction. The Pelli-Robson test was used to determine binocular contrast sensitivity at various spatial frequencies, and the NEI VFQ-25 questionnaire was applied before surgery (pre-test) and three months after surgery (post-test). Statistical analysis was based on the paired T-test with a significance level of 95 percent. Results: Mean age was 28.73 ± 5.85 years. Female sex prevailed (71.43 percent). Significant differences were found in all the spatial frequencies of binocular contrast sensitivity between the pre- and postoperative periods (p < 0.01). Comparison of pre- and post-test results (retrospective assessment of presurgical quality of life) did not find any significant differences, indicating that there was no recalibration. Significant differences with respect to the post-test confirm the actual change in these patients' quality of life after surgery. Conclusions: ACR-128 phakic lens implantation for high myopia correction improves vision-related quality of life without changes in its perception before and after surgery(AU)

Identification and functional characterization of odorant-binding proteins 69a and 76a of Drosophila suzukii.

The fruit fly Drosophila suzukii is a fruit crop pest that causes a severe economic threat to soft summer fruit worldwide. The male sex pheromone, cis-vaccenyl acetate (cVA) has multiple functions in intra-species communication in Drosophila melanogaster, which is required in male to suppress male-male courtship. D. suzukii males do not produce cVA; however, the odorant receptor for cVA (Or67d) is still functional. The lack of cVA in D. suzukii casts the question of whether this pheromone might have been replaced by another compound similar to cVA that disrupts mating in D. suzukii. In order to address this question, we cloned two D. suzukii adult antenna-specific odorant-binding proteins (OBPs) DsOBP69a and DsOBP76a and aligned with their D. melanogaster orthologues. Moreover, we examined the binding properties of the newly identified recombinant proteins against 26 potential ligands including cVA, using the fluorescence-based ligand binding assay. The alignment showed that DsOBP69a and DsOBP76a, have six conserved cysteines and belong to the classic OBP family. Furthermore, our results revealed that cVA did not bind to DsOBP69a or DsOBP76a proteins. Interestingly, the floral odorant ß-ionone and the bitter substance berberine chloride and coumarin displayed high binding ability. It is also worth noting that DsOBP69a and DsOBP76a have different affinities to (Z)-7-Tricosene that may reflect different functional roles. These findings suggest that DsOBP69a and DsOBP76a are potentially involved in olfaction and gustation of D. suzukii.

GM-CSF instigates a dendritic cell-T-cell inflammatory circuit that drives chronic asthma development.

BACKGROUND: Steroid-resistant asthma is often characterized by high levels of neutrophils and mixed TH2/TH17 immune profiles. Indeed, neutrophils are key drivers of chronic lung inflammation in multiple respiratory diseases. Their numbers correlate strongly with disease severity, and their presence is often associated with exacerbation of chronic lung inflammation. OBJECTIVE: What factors drive development of neutrophil-mediated chronic lung disease remains largely unknown, and we sought to study the role of GM-CSF as a potential regulator in chronic asthma. METHODS: Different experimental animal models of chronic asthma were used in combination with alveolar macrophage-reconstitution of global GM-CSF receptor knockout mice as well as cell-type-specific knockout animals to elucidate the role of GM-CSF signaling in chronic airway inflammation. RESULTS: We identify GM-CSF signaling as a critical factor regulating pulmonary accumulation of neutrophils. We show that although being not required for intrinsically regulating neutrophil migration, GM-CSF controls lung dendritic cell function, which in turn promotes T-cell-dependent recruitment of neutrophils to the airways. We demonstrate that GM-CSF regulates lung dendritic cell antigen uptake, transport, and TH2/TH17 cell priming in an intrinsic fashion, which in turn drives pulmonary granulocyte recruitment and contributes to development of airway hyperresponsiveness in chronic disease. CONCLUSIONS: We identify GM-CSF as a potentially novel therapeutic target in chronic lung inflammation, describing a GM-CSF-dependent lung conventional dendritic cell-T-cell-neutrophil axis that drives chronic lung disease.

Calidad de vida y visual en pacientes con implante de lente intraocular fáquico / Visual acuity and quality of life of patients undergoing phakic intraocular lens implantation

RESUMEN Los errores refractivos altos son difíciles de corregir óptica y quirúrgicamente. Los pacientes que los padecen se encuentran incómodos con las gafas, ya que la calidad de su visión es deficitaria. Las lentes de contacto proporcionan mejor agudeza visual; sin embargo, en ocasiones requieren diseños especiales para ser adaptadas y pueden asociarse a complicaciones severas. La cirugía refractiva como subespecialidad busca mejorar la agudeza visual no corregida y disminuir la dependencia a gafas o lentes de contacto. Las opciones van desde los procedimientos queratorrefractivos hasta el implante de una lente intraocular, ya sea con la extracción del cristalino transparente o en un ojo fáquico. Este último ofrece ventajas al mantener la acomodación, obtener una mejor calidad óptica y cierta reversibilidad. En el mundo se han realizado múltiples trabajos en pacientes con lentes fáquicos de diferentes modelos y estos han demostrado que son seguros y confiables, aunque no son muchos los estudios sobre la calidad de vida a largo plazo; de ahí la motivación para realizar una búsqueda actualizada de diversos artículos publicados, con el objetivo de describir los resultados visuales y la calidad de vida en pacientes con implante de lentes fáquicos. Se utilizó la plataforma Infomed, específicamente la Biblioteca Virtual de Salud, con todos sus buscadores(AU)

ABSTRACT High refractive errors are difficult to correct both optically and surgically. Patients suffering from them feel uncomfortable with their eyeglasses, since their visual quality is poor. Contact lenses provide better visual acuity, but they sometimes require special designs to be adjusted and may be associated to severe complications. The subspecialty of refractive surgery seeks to improve uncorrected visual acuity and reduce dependence on eyeglasses or contact lenses. Options range from keratorefractive procedures to intraocular lens implantation, be it with removal of the transparent crystalline lens or in phakic eyes. The latter provides the advantages of maintaining accommodation, obtaining better visual quality and affording a certain degree of reversibility. A great many studies have been conducted worldwide of patients with phakic lenses of various models, and these have proved to be safe and reliable. However, not many studies are available about long-term quality of life. Hence the motivation to perform an updated search for published papers about the subject, with the purpose of describing the visual results and quality of life of patients with phakic lens implants. Use was made of the Infomed platform, particularly the Virtual Health Library with all its search engines(AU)

Fetal monocytes possess increased metabolic capacity and replace primitive macrophages in tissue macrophage development.

Tissue-resident macrophages (MΦTR ) originate from at least two distinct waves of erythro-myeloid progenitors (EMP) arising in the yolk sac (YS) at E7.5 and E8.5 with the latter going through a liver monocyte intermediate. The relative potential of these precursors in determining development and functional capacity of MΦTR remains unclear. Here, we studied development of alveolar macrophages (AM) after single and competitive transplantation of different precursors from YS, fetal liver, and fetal lung into neonatal Csf2ra-/- mice, which lack endogenous AM. Fetal monocytes, promoted by Myb, outcompeted primitive MΦ (pMΦ) in empty AM niches and preferentially developed to mature AM, which is associated with enhanced mitochondrial respiratory and glycolytic capacity and repression of the transcription factors c-Maf and MafB. Interestingly, AM derived from pMΦ failed to efficiently clear alveolar proteinosis and protect from fatal lung failure following influenza virus infection. Thus, our data demonstrate superior developmental and functional capacity of fetal monocytes over pMΦ in AM development and underlying mechanisms explaining replacement of pMΦ in fetal tissues.

Innate-like Lymphocytes and Innate Lymphoid Cells in Asthma.

Asthma is a chronic pulmonary disease, highly associated with immune disorders. The typical symptoms of asthma include airway hyperresponsiveness (AHR), airway remodeling, mucus overproduction, and airflow limitation. The etiology of asthma is multifactorial and affected by genetic and environmental factors. Increasing trends toward dysbiosis, smoking, stress, air pollution, and a western lifestyle may account for the increasing incidence of asthma. Based on the presence or absence of eosinophilic inflammation, asthma is mainly divided into T helper 2 (Th2) and non-Th2 asthma. Th2 asthma is mediated by allergen-specific Th2 cells, and eosinophils activated by Th2 cells via the secretion of interleukin (IL)-4, IL-5, and IL-13. Different from Th2 asthma, non-Th2 asthma shows little eosinophilic inflammation, resists to corticosteroid treatment, and occurs mainly in severe asthmatic patients. Previous studies of asthma primarily focused on the function of Th2 cells, but, with the discovery of non-Th2 asthma and the involvement of innate lymphoid cells (ILCs) in the pathogenesis of asthma, tissue-resident innate immune cells in the lung have become the focus of attention in asthma research. Currently, innate-like lymphocytes (ILLs) and ILCs as important components of the innate immune system in mucosal tissues are reportedly involved in the pathogenesis of or protection against both Th2 and non-Th2 asthma. These findings of the functions of different subsets of ILLs and ILCs may provide clues for the treatment of asthma.

A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.

The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-ß) from latent complexes via integrin-αV activation. Using acute injury models in two different tissues, we found that by inducing TGF-ß activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration after acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation.

Selection and evaluation of reference genes for expression analysis using quantitative real-time PCR in the Asian Ladybird Harmonia axyridis (Coleoptera: Coccinellidae).

Harmonia axyridis (Coleoptera: Coccinellidae) is a polyphagous insect that is an important biological agent used to control agricultural and forestry pests. The role of functional genes in H. axyridis based on quantitative real-time PCR (qRT-PCR) is increasingly well understood to investigate biology, physiology, feeding behavior and the role of important genes in physiological processes. Quantitative real-time PCR (qRT-PCR) is a powerful and reliable technique to quantify gene expression. Using qRT-PCR, expression levels of target genes are determined based on the levels of internal reference genes; therefore, reference genes need to be stably expressed under specific experimental conditions. However, there have been no studies on the stability of reference genes used in H. axyridis. In this study, we systematically investigated expression profiles of nine candidate reference genes from H. axyridis, including ß-actin (ACTIN); elongation factor 1 α (EF1A); ribosomal proteins L10, L18, L28, S13, and S15 (RPL10, RPL18, RPL28, RPS13 and RPS15); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); and superoxide dismutase (SOD). Four analytical methods (geNorm, BestKeeper, NormFinder, and the ΔCt method) were used to evaluate the suitability of these genes as internal reference genes for three biotic factors (developmental stage, tissue, and sex) and two abiotic treatments (temperature and photoperiod). RefFinder, a comprehensive evaluation platform integrating the four analytical methods, was used to rank the overall stability of these reference genes. Among the nine candidate genes, different reference genes were identified as having the most stable expression across biotic and abiotic factors. Genes encoding ribosomal proteins typically had the most stable expression, though EF1A was the most stable across developmental stages and photoperiods. To validate the suitability of these reference genes, heat shock protein 90 (HSP90) was chosen as a target. Significant up-regulation in HSP90 expression level in response to both low and high temperature was observed when using the most suitable reference genes but not when using an arbitrarily selected reference gene. The reference genes identified in this study will provide the basis for future functional genomics research in H. axyridis and will also facilitate the establishment of a standardized qRT-PCR program for other related insects.

Effect of 131I 'clear residual thyroid tissue' after surgery on the function of parathyroid gland in differentiated thyroid cancer.

Thyroid cancer is a common malignant tumor of the endocrine glands. Although surgery is the optimal treatment utilized, the disease is characterized by recurrence and metastasis. The aim of the present study was to determine the effect of iodine-131 (131I) 'clear residual thyroid tissue' following surgery on the treatment of differentiated thyroid cancer (DTC) and its effect on the function of the parathyroid gland. A total of 160 patients diagnosed with DTC, who were consecutively admitted to our Hospital between June 2012 and June 2014 and underwent total thyroidectomy or subtotal resection, were included in the present study. After three months, the patients were administered 131I 'clear residual thyroid tissue' treatment and underwent a whole body scan after 1 week to determine whether 'clear residual thyroid tissue' treatment was successful or not. The treatment was repeated within 3 months if not successful. Of the 160 patients, 24 patients had cancer metastasis (15.0%). The average dose of 131I used for the first time was 6.4+1.2 GBq and the treatment was successful in 66 cases (41.3%). The average treatment time was 2.8±0.6 therapy sessions. The results showed that, prior to and following the first treatment and at the end of the follow up, levels of the parathyroid hormone, serum calcium and phosphorus were compared, and no statistically significant difference (P>0.05) was observed. There were 5 patients with persistent hypothyroidism and 8 patients with transient hypothyroidism. The levels of thyroglobulin were significantly decreased, and the difference was statistically significant (P<0.05). A total of 48 patients (30%) with hypothyroidism were identified. In conclusion, the results have shown that DTC resection and 131I 'clear residual thyroid tissue' treatment did not significantly impair the parathyroid function, thereby improving the treatment effect.

Overexpression of histone demethylase JMJD5 promotes metastasis and indicates a poor prognosis in breast cancer.

In this study, we showed the expression of JMJD5 was increased in breast cancer tissues and breast adenocarcinoma cell lines MCF-7 as well as triple negative breast cancer cell lines MDA-MB-231 compared with paired adjacent normal mammary tissues and normal mammary epithelial cell lines MCF-10A. The higher expression of JMJD5 was significantly corresponded with clinical stage, histological grade and lymph node metastasis. Overexpression of JMJD5 promoted cell invasion and induce EMT, while JMJD5 siRNA inhibits MDA-MB-231 cells invasion in vitro. Moreover, qChIP analysis revealed the Snail family proteins Snai1 was the direct target of JMJD5 in breast cancer cells. Luciferase reporter assays suggested that the overexpression of JMJD5 resulted in the activation of Snail1 promoter-driven luciferase reporter. The changes in the level of RNA and protein implied that the activation of Snail was the important mechanisms by which JMJD5 triggers metastasis. We also detected the higher expression of JMJD5 protein was an independent unfavorable biomarker for worse overall survival in breast cancer patients. Therefore, our results identified an important role for JMJD5 in breast cancer through the regulation of snail1.