Plant hormesis: Revising of the concepts of biostimulation, elicitation and their application in a sustainable agricultural production.

Current research in basic and applied knowledge of plant science has aimed to unravel the role of the interaction between environmental factors and the genome in the physiology of plants to confer the ability to overcome challenges in a climate change scenario. Evidence shows that factors causing environmental stress (stressors), whether of biological, chemical, or physical origin, induce eustressing or distressing effects in plants depending on the dose. The latter suggests the induction of the "hormesis" phenomenon. Sustainable crop production requires a better understanding of hormesis, its basic concepts, and the input variables to make its management feasible. This implies that acknowledging hormesis in plant research could allow specifying beneficial effects to effectively manage environmental stressors according to cultivation goals. Several factors have been useful in this regard, which at low doses show beneficial eustressing effects (biostimulant/elicitor), while at higher doses, they show distressing toxic effects. These insights highlight biostimulants/elicitors as tools to be included in integrated crop management strategies for reaching sustainability in plant science and agricultural studies. In addition, compelling evidence on the inheritance of elicited traits in plants unfolds the possibility of implementing stressors as a tool in plant breeding.

A Timeline of Perezone, the First Isolated Secondary Metabolite in the New World, Covering the Period from 1852 to 2020.

This chapter covers a sesquiterpene quinone, commonly named perezone. This molecule is documented as the first secondary metabolite isolated in crystalline form in the New World in 1852. An introduction, with its structure, the IUPAC nomenclature, and the most recent physical and spectroscopic characterizations are firstly described initially. Alongside this, a timeline and scheme with summarized information of the history of this molecule is given including the "Códice Badiano de la Cruz, 1552, highlighting the year of its isolation culminating with information up to 2005. Subsequently, in a chronological order the most recent advances of the target molecule are included and organized in subsections covering the last 15-year period 2006-2020. Finally, recently submitted contributions from the laboratory of the authors are described. It is important to note that the details provided highlight the importance and relevance of perezone.

Diagnostic Accuracy of the Panbio Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Rapid Test Compared with Reverse-Transcriptase Polymerase Chain Reaction Testing of Nasopharyngeal Samples in the Pediatric Population.

We conducted a multicenter clinical validity study of the Panbio coronavirus disease 2019 Antigen Rapid Test of nasopharyngeal samples in pediatric patients with coronavirus disease 2019-compatible symptoms of ≤5 days of evolution. Our study showed limited accuracy in nasopharyngeal antigen testing: overall sensitivity was 45.4%, and 99.8% of specificity, positive-predictive value was 92.5%.

The TGF-ß profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.

Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-ß and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-ß on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-ß results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-ß with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-ß was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-ß in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-ß cascade and is a traceable marker of progressive DN.

Intraglomerular Monocyte/Macrophage Infiltration and Macrophage-Myofibroblast Transition during Diabetic Nephropathy Is Regulated by the A2B Adenosine Receptor.

Diabetic nephropathy (DN) is considered the main cause of kidney disease in which myofibroblasts lead to renal fibrosis. Macrophages were recently identified as the major source of myofibroblasts in a process known as macrophage-myofibroblast transition (MMT). Adenosine levels increase during DN and in vivo administration of MRS1754, an antagonist of the A2B adenosine receptor (A2BAR), attenuated glomerular fibrosis (glomerulosclerosis). We aimed to investigate the association between A2BAR and MMT in glomerulosclerosis during DN. Kidneys/glomeruli of non-diabetic, diabetic, and MRS1754-treated diabetic (DM+MRS1754) rats were processed for histopathologic, transcriptomic, flow cytometry, and cellular in vitro analyses. Macrophages were used for in vitro cell migration/transmigration assays and MMT studies. In vivo MRS1754 treatment attenuated the clinical and histopathological signs of glomerulosclerosis in DN rats. Transcriptomic analysis demonstrated a decrease in chemokine-chemoattractants/cell-adhesion genes of monocytes/macrophages in DM+MRS1754 glomeruli. The number of intraglomerular infiltrated macrophages and MMT cells increased in diabetic rats. This was reverted by MRS1754 treatment. In vitro cell migration/transmigration decreased in macrophages treated with MRS1754. Human macrophages cultured with adenosine and/or TGF-ß induced MMT, a process which was reduced by MRS1754. We concluded that pharmacologic blockade of A2BAR attenuated some clinical signs of renal dysfunction and glomerulosclerosis, and decreased intraglomerular macrophage infiltration and MMT in DN rats.

Primary antiphospholipid syndrome, Addison disease, and adrenal incidentaloma.

Primary adrenal failure comprises an insufficient production of mineralocorticoids and glucocorticoids in the adrenal cortex. A rare manifestation of antiphospholipid syndrome (APS) is adrenal failure. The majority of patients with adrenal involvement in APS develop an irreversible cortisol deficiency and atrophy of the adrenal glands. Adrenal incidentalomas are adrenal masses larger than 1 cm that are discovered in the course of diagnostic evaluation or treatment for another medical condition. Its prevalence is calculated in 1.5-9% of individuals. We describe an exceptional case of a 23-year-old male patient with APS with persistent high levels of antiphospholipid antibodies (aPL) from the time of diagnosis, who developed Addison's disease as a manifestation of APS with atrophy of the adrenal glands, in whom an adrenal incidentaloma was developed later and was corroborated as an aldosterone-producing adenoma. Currently, the patient is asymptomatic and without manifestations of tumor recurrence. The protumoral effect of elevated and persistent aPL is discussed.

Left thoracotomy approach for off-pump coronary artery bypass grafting surgery: 15 years of experience in 2500 consecutive patients.

OBJECTIVES: Our goal was to describe the experience at 2 centres with off-pump coronary artery bypass grafting using a left thoracotomy. METHODS: From January 2002 to December 2017, a total of 2528 consecutive patients (578 women, mean age 62.3 ± 9.1 years) were operated on using this technique. Data were collected prospectively and analysed retrospectively. RESULTS: There were no conversions to median sternotomy and 6 patients (0.2%) were converted to on-pump CABG. The mean number of grafts per patient was 2.8 ± 0. 9. The 30-day mortality rate was 1.0% (25 patients). Most patients were extubated in the operating theatre (97.3%), and 47 patients (1.9%) needed re-exploration for bleeding. Seven patients (0.3%) experienced a cerebrovascular event; 4 (0.3%) had a postoperative myocardial infarction; and 84 (3.4%) had new-onset atrial fibrillation. A total of 1510 patients (61.1%) were discharged from the hospital in the first 48 h after surgery. Long-term survival rates were 98.8%, 93.6% and 69.1% at 1, 5 and 10 years, respectively (central image). During the follow-up period, 60 patients (2.9%) were re-examined for recurrence of angina with a new coronary angiogram; of those, 24 (1.2%) required percutaneous coronary intervention and 11 (0.5%) had redo surgery. CONCLUSIONS: A left thoracotomy is a safe alternative to a median sternotomy for coronary artery bypass grafting on the beating heart, with low early complications and good mid- and long-term results.

Probiotics' effectiveness on symptoms, histological features and feeding tolerance in ulcerative colitis / Efectividad de probióticos sobre síntomas, histología y tolerancia alimentaria en colitis ulcerativa

Background: Probiotics have been used in the adjuvant treatment of Ulcerative Colitis (UC). Objective: To evaluate the role of a combination of probiotics on the clinical, histological changes and feeding tolerance in patients with UC. Methods: An open UC patients with mild to moderate activity and clinical trial was conducted. Patients were randomized to receive or a combination of 6 strains of probiotics for 3 months while continuing their drug treatment established. UC activity was assessed by Truelove and Witts scale and histological findings by Gupta index. Descriptive statistics, Chi square test and Student t test for comparison of the two groups was performed. Results: In each group 17 patients were included. An improvement was found in the disease activity (52.9% vs. 23.5%, p = 0.07) and in histologic index (82.3% vs. 41.1%, p = 0.03) in patients treated with probiotics compared to the control group. Improved food tolerance was also observed in patients treated with probiotics. Conclusion: The study shows a beneficial short-term effect on symptoms, histological findings and feeding tolerance with the administration of a combination of 6 strains of probiotics in patients with UC.

Introducción: los probióticos han sido utilizados en el tratamiento adyuvante de la colitis ulcerativa (CU). Objetivo: evaluar el papel de una combinación de probióticos sobre las manifestaciones clínicas, cambios histológicos y tolerancia alimentaria en pacientes con CU. Métodos: se realizó un ensayo clínico abierto de pacientes con CU y actividad leve a moderada. Los pacientes se aleatorizaron para recibir, o no, una combinación de 6 cepas de probióticos durante 3 meses, mientras continuaban con el tratamiento farmacológico establecido. Se evaluó la actividad de la CU mediante la escala de Truelove and Witts, y los hallazgos histológicos mediante el índice de Gupta. Se realizó estadística descriptiva, prueba de Chi cuadrada y t de Student para la comparación de ambos grupos. Resultados: se incluyeron 17 pacientes por grupo. Se encontró una mejoría en la actividad de la enfermedad (52.9% frente a 23.5%, p = 0.07) y en el índice histológico (82.3% frente a 41.1%, p = 0.03) en los pacientes tratados con probióticos en comparación con el grupo control. También se observó una mejor tolerancia alimentaria en los pacientes tratados con probióticos. Conclusión: el estudio muestra un efecto benéfico a corto plazo sobre los síntomas, hallazgos histológicos y tolerancia alimentaria con la administración de una combinación de 6 cepas de probióticos en pacientes con CU.

Púrpura de Henoch-Schönlein como manifestación inicial de mieloma múltiple / Henoch-Schonlein purpura as initial manifestation of multiple myeloma

Resumen La púrpura de Henoch-Schönlein como vasculitis paraneoplásica de tumores sólidos se encuentra en 9 a 11% de los casos reportados en adultos con carcinoma de estómago, mama, pulmón, próstata o riñón; es poco frecuente como paraneoplásico de mieloma múltiple. Se comunica el caso de una paciente que padeció púrpura de Henoch-Schönlein como manifestación inicial de mieloma múltiple.

Abstract Henoch-Schonlein purpura as paraneoplasic vasculitis of solid tumors is found in 9-11% of cases reported in adults with stomach, breast, lung, prostate and kidney carcinomas; it is little frequent as paraneoplastic of multiple myeloma. This paper reports the case of a patient that suffered from Henoch-Schonlein purpura as initial manifestation of multiple myeloma.

Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration.

The early endosome protein Rab5 was recently shown to promote cell migration by enhancing focal adhesion disassembly through mechanisms that remain elusive. Focal adhesion disassembly is associated to proteolysis of talin, in a process that requires calpain2. Since calpain2 has been found at vesicles and endosomal compartments, we hypothesized that Rab5 stimulates calpain2 activity, leading to enhanced focal adhesion disassembly in migrating cells. We observed that calpain2 co-localizes with EEA1-positive early endosomes and co-immunoprecipitates with EEA1 and Rab5 in A549 lung carcinoma cells undergoing spreading, whereas Rab5 knock-down decreased the accumulation of calpain2 at early endosomal-enriched fractions. In addition, Rab5 silencing decreased calpain2 activity, as shown by cleavage of the fluorogenic substrate tBOC-LM-CMAC and the endogenous substrate talin. Accordingly, Rab5 promoted focal adhesion disassembly in a calpain2-dependent manner, as expression of GFP-Rab5 accelerated focal adhesion disassembly in nocodazole-synchronized cells, whereas pharmacological inhibition of calpain2 with N-acetyl-Leu-Leu-Met prevented both focal adhesion disassembly and cell migration induced by Rab5. In summary, these data uncover Rab5 as a novel regulator of calpain2 activity and focal adhesion proteolysis leading to cell migration.

The salivary peptide histatin-1 promotes endothelial cell adhesion, migration, and angiogenesis.

Saliva is a key factor that contributes to the high efficiency of wound healing in the oral mucosa. This is not only attributed to physical cues but also to the presence of specific peptides in the saliva, such as histatins. Histatin-1 is a 38 aa antimicrobial peptide, highly enriched in human saliva, which has been previously reported to promote the migration of oral keratinocytes and fibroblasts in vitro However, the participation of histatin-1 in other crucial events required for wound healing, such as angiogenesis, is unknown. Here we demonstrate that histatin-1 promotes angiogenesis, as shown in vivo, using the chick chorioallantoic membrane model, and by an in vitro tube formation assay, using both human primary cultured endothelial cells (HUVECs) and the EA.hy926 cell line. Specifically, histatin-1 promoted endothelial cell adhesion and spreading onto fibronectin, as well as endothelial cell migration in the wound closure and Boyden chamber assays. These actions required the activation of the Ras and Rab interactor 2 (RIN2)/Rab5/Rac1 signaling axis, as histatin-1 increased the recruitment of RIN2, a Rab5-guanine nucleotide exchange factor (GEF) to early endosomes, leading to sequential Rab5/Rac1 activation. Accordingly, interfering with either Rab5 or Rac1 activities prevented histatin-1-dependent endothelial cell migration. Finally, by immunodepletion assays, we showed that salivary histatin-1 is required for the promigratory effects of saliva on endothelial cells. In conclusion, we report that salivary histatin-1 is a novel proangiogenic factor that may contribute to oral wound healing.-Torres, P., Díaz, J., Arce, M., Silva, P., Mendoza, P., Lois, P., Molina-Berríos, A., Owen, G. I., Palma, V., Torres, V. A. The salivary peptide histatin-1 promotes endothelial cell adhesion, migration, and angiogenesis.

ATP Induces IL-1ß Secretion in Neisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis.

Neisseria gonorrhoeae (Ngo) has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses. Recent findings have reported that Ngo reduces the IL-1ß secretion of infected human monocyte-derived macrophages (MDM). Here, we investigate the role of adenosine triphosphate (ATP) in production and release of IL-1ß in Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1ß levels about ten times compared with unexposed Ngo-infected MDM (P < 0.01). However, we did not observe any changes in inflammasome transcriptional activation of speck-like protein containing a caspase recruitment domain (CARD) (ASC, P > 0.05) and caspase-1 (CASP1, P > 0.05). In addition, ATP was not able to modify caspase-1 activity in Ngo-infected MDM but was able to increase pyroptosis (P > 0.01). Notably ATP treatment defined an increase of positive staining for IL-1ß with a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1ß secretion by a mechanism not related to the NLRP3/ASC/caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation.

Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.

Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis.

[Atrophy in the mucosa neighboring an intestinal-type gastric adenocarcinoma by comparing the Sydney vs. OLGA systems]. / Atrofia circundante al adenocarcinoma gástrico tipo intestinal. Rendimiento diagnóstico de Sídney y Olga.

BACKGROUND: Gastric carcinoma causes about 700 000 deaths worldwide per year. Is feasible detect it in earlier stages. The aim of this article is to assess the atrophy in the mucosa neighboring an intestinal-type gastric adenocarcinoma by comparing the Sydney vs. OLGA systems. METHODS: Twenty-eight individuals with intestinal-type gastric adenocarcinoma (Lauren) were compared with 32 non-neoplastic cases. Both groups had undergone total gastrectomy. Two pathologists made a consensus-based assessment of the atrophy in non-neoplastic corpus and antral epithelium using the Sydney and OLGA Systems. The mean, median, and distribution of the frequencies were obtained using the measuring and distribution scales of the study variables. The sensitivity, specificity, and predictive values, both positive and negative, for gastric cancer were calculated through the dichotomy of advanced atrophy-positive and advanced atrophy-negative scales. RESULTS: Twenty-four of the 28 cases with intestinal-type gastric carcinoma showed an advanced atrophy with the OLGA system, with a sensitivity and specificity of 77 and 85 %, respectively. Conversely, 4 of the 28 individuals showed an advanced atrophy with the Sydney system, with a sensitivity and specificity of 14 and 100 %, respectively. CONCLUSIONS: The OLGA system has a high sensitivity and specificity (77 y 85 % respectively) for the recognition of preneoplastic changes in the mucosa neighboring a gastric carcinoma.

Introducción: el carcinoma gástrico ocasiona al año unas 700 000 muertes en el mundo. El objetivo de este artículo es evaluar la atrofia en la mucosa vecina al adenocarcinoma gástrico tipo intestinal comparando los sistemas Sídney y OLGA. Diferencias en el rendimiento diagnóstico impulsarían el empleo de alguno. Métodos: estudiamos 28 sujetos con adenocarcinoma gástrico tipo intestinal (Lauren), que comparamos con 32 casos sin neoplasia, ambos grupos con gastrectomía total. Dos patólogos evaluaron la atrofia en el epitelio de cuerpo y antro no neoplásico con los sistemas Sídney y OLGA. Se obtuvieron la media, mediana y distribución de frecuencias por escala de medición, así como la distribución de las variables del estudio. Se calculó la sensibilidad, especificidad y los valores predictivos para cáncer gástrico gracias a dicotomizar las escalas con resultado positivo y negativo para atrofia avanzada. Resultados: veinticuatro de 28 casos con adenocarcinoma gástrico tipo intestinal mostraron atrofia avanzada con OLGA con una sensibilidad y especificidad de 77 y 85 % respectivamente. Con el sistema Sídney, 4 de 28 mostraron atrofia avanzada con una sensibilidad y especificidad de 14 y 100 % respectivamente. Conclusiones: el sistema OLGA tiene elevada sensibilidad y especificidad (77 y 85 % respectivamente) para reconocer cambios preneoplásicos en la mucosa vecina al cáncer gástrico. Empero, OLGA no mostró atrofia avanzada en adenomas foveolares con displasia de alto grado, ni en adenocarcinomas en las porciones proximales del estómago.

Anal intraepithelial neoplasia among HIV-positive men who have sex with men.

Neoplasia is the second most common cause of mortality in HIV patients. The prevalence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of antiretroviral therapy. We screened 94 HIV-infected MSM patients. We found high-grade squamous intraepithelial lesions (HSIL) in six of the patients. The calculated prevalence of HSIL was 6.4% (95% confidence interval: 2.9-13.2). The study and implementation of screening programs for high-risk groups is a priority.

Down-regulation of Rab5 decreases characteristics associated with maintenance of cell transformation.

The early endosomal protein Rab5 is highly expressed in tumor samples, although a causal relationship between Rab5 expression and cell transformation has not been established. Here, we report the functional effects of targeting endogenous Rab5 with specific shRNA sequences in different tumor cell lines. Rab5 down-regulation in B16-F10 cells decreased tumor formation by subcutaneous injection into C57/BL6 mice. Accordingly, Rab5 targeting in B16-F10 and A549, but not MDA-MB-231 cells was followed by decreased cell proliferation, increased apoptosis and decreased anchorage-independent growth. These findings suggest that Rab5 expression is required to maintain characteristics associated with cell transformation.

Accuracy of body mass index for age to diagnose obesity in Mexican schoolchildren.

OBJECTIVE: To compare the accuracy of three BMI-forage references (World Health Organization reference, WHO; the updated International Obesity Task Force reference, IOTF; and Centers for Disease Control and Prevention (CDC) growth charts) to diagnose obesity in Mexican children. METHODS: A convenience sample of Mexican schoolchildren (n = 218) was assessed. The gold standard was the percentage of body fat estimated by deuterium dilution technique. Sensitivity and specificity of the classical cutoff point of BMI-for-age to identify obesity (i.e. > 2.00 standard deviation, SD) were estimated. The accuracy (i.e. area under the curve, AUC) of three BMI-for-age references for the diagnosis of obesity was estimated with the receiver operating characteristic (ROC) curves method. The optimal cutoff point (OCP) was determined. RESULTS: The cutoff points to identify obesity had low (WHO reference: 57.6%, CDC: 53.5%) to very low (IOTF reference: 40.4%) sensitivities, but adequate specificities (91.6%, 95.0%, and, 97.5%, respectively). The AUC of the three references were adequate (0.89). For the IOTF reference, the AUC was lower among the older children. The OCP for the CDC reference (1.24 SD) was lower than the OCP for WHO (1.53 SD) and IOTF charts (1.47 SD). CONCLUSIONS: The classical cutoff point for obesity has low sensitivity--especially for the IOTF reference. The accuracy of the three references was similar. However, to obtain comparable diagnosis of obesity different cutoff points should be used depending of the reference.

Objetivo: comparar la exactitud de tres referencias del IMC para la edad (de la Organización Mundial de la Salud, OMS; de la International Obesity Task Force, IOTF; y de los Centros para el Control y Prevención de Enfermedades (CDC) de las tablas de crecimiento) para diagnosticar obesidad en niños mexicanos. Métodos: se evaluó una muestra por conveniencia de escolares de la ciudad de México (n = 218). El estándar de oro fue el porcentaje de grasa corporal estimado por la técnica de dilución de deuterio. Se estimaron la sensibilidad y la especificidad del punto de corte clásico del IMC para la edad para identificar obesidad (i.e. > 2.0 desviaciones estándar, DE). La exactitud (i.e., área bajo la curva, ABC) de las tres referencias del IMC para el diagnóstico de la obesidad se estimó con el método de curvas ROC. Se identificó el punto de corte óptimo (PCO). Resultados: los puntos de corte para identificar obesidad tuvieron baja (OMS: 57.6% y CDC: 53.5%) o muy baja (IOTF referencia: 40,4%) sensibilidad, pero especificidades adecuadas (91.6%, 95.0% y 97.5%, respectivamente). El ABC de las tres referencias fueron adecuadas (0.89). Entre los niños mayores la referencia de la IOTF tuvo el menor ABC. El PCO para la referencia de los CDC (1.24 DE) fue menor que el PCO para la de la OMS (1.53 DE) y la de la IOTF (1.47 DE). Conclusiones: el punto de corte clásico para la obesidad tiene baja sensibilidad, especialmente para la referencia de la IOTF. La exactitud de las tres referencias fue similar. Sin embargo, para obtener el diagnóstico comparable de obesidad en diferentes puntos de corte se debe utilizar en función de la referencia seleccionada.

Rab5 activation as a tumor cell migration switch.

Increased cell migration is an acquired feature of metastatic cancer cells and relies on derailed signal transduction pathways. Intracellular vesicular trafficking plays a key role in cell migration due to its intricate involvement in cargo transport and membrane composition. In the last decade, endocytosis has been implicated in cell migration and found to be responsible for the internalization of membrane receptors at the plasma membrane, where integrin trafficking and fine-tuning of receptor tyrosine kinase signaling by internalization are major mechanisms. Accumulating evidence has suggested a link between endosome dynamics, cell migration, and invasion, in which small GTPases of the Rab family have central roles. We have recently determined that Rab5 activation is a crucial event in promoting focal adhesion disassembly, which is concomitant with the migration and invasion of metastatic cancer cells. The mechanisms underlying this novel role for Rab5 are currently unclear, and their elucidation will provide insight into the role of Rab5 function in cancer cell metastasis.

Rab5 activation as a tumor cell migration switch.

Increased cell migration is an acquired feature of metastatic cancer cells and relies on derailed signal transduction pathways. Intracellular vesicular trafficking plays a key role in cell migration due to its intricate involvement in cargo transport and membrane composition. In the last decade, endocytosis has been implicated in cell migration and found to be responsible for the internalization of membrane receptors at the plasma membrane, where integrin trafficking and fine-tuning of receptor tyrosine kinase signaling by internalization are major mechanisms. Accumulating evidence has suggested a link between endosome dynamics, cell migration, and invasion, in which small GTPases of the Rab family have central roles. We have recently determined that Rab5 activation is a crucial event in promoting focal adhesion disassembly, which is concomitant with the migration and invasion of metastatic cancer cells. The mechanisms underlying this novel role for Rab5 are currently unclear, and their elucidation will provide insight into the role of Rab5 function in cancer cell metastasis.

Rab5 activation promotes focal adhesion disassembly, migration and invasiveness in tumor cells.

Migration and invasion are essential steps associated with tumor cell metastasis and increasing evidence points towards endosome trafficking being essential in this process. Indeed, the small GTPase Rab5, a crucial regulator of early endosome dynamics, promotes cell migration in vitro and in vivo. Precisely how Rab5 participates in these events remains to be determined. Considering that focal adhesions represent structures crucial to cell migration, we specifically asked whether Rab5 activation promoted focal adhesion disassembly and thereby facilitated migration and invasion of metastatic cancer cells. Pulldown and biosensor assays revealed that Rab5-GTP loading increased at the leading edge of migrating tumor cells. Additionally, targeting of Rab5 by different shRNA sequences, but not control shRNA, decreased Rab5-GTP levels, leading to reduced cell spreading, migration and invasiveness. Re-expression in knockdown cells of wild-type Rab5, but not the S34N mutant (GDP-bound), restored these properties. Importantly, Rab5 association with the focal adhesion proteins vinculin and paxillin increased during migration, and expression of wild-type, but not GDP-bound Rab5, accelerated focal adhesion disassembly, as well as FAK dephosphorylation on tyrosine 397. Finally, Rab5-driven invasiveness required focal adhesion disassembly, as treatment with the FAK inhibitor number 14 prevented Matrigel invasion and matrix metalloproteinase release. Taken together, these observations show that Rab5 activation is required to enhance cancer cell migration and invasion by promoting focal adhesion disassembly.