•An immune-modulator was prepared by concentrating cytokines and growth factors in urine.•It can boost immunomodulatory responses in allergic and autoimmune disease patients.•The immune-modulator is ...administrated sublingually.•This strategy aims to boost the immunomodulatory response of the treated patients.
At “Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C.” in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an “immune-modulator” has been developed. In this study, we will refer to this treatment substance as the “immune-modulator.” In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator.
Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay.
Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1β, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65–70% of samples; IL5, IL-1B, and IL-17 in 50–60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20–30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1β, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment.
The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.
The objectives were to assess the following: (1) the relationship between sward height and chemical composition of four pasture types in association with grazing behaviour and body condition score ...(BCS) of dairy cows, and (2) the possibility of developing predictive equations of the nutrient intake and grazing behaviour within a continued grazing system. Pasture type had a significant (p < 0.01) effect on nutrient supply from January to June for all pastures investigated. Ryegrass–white clover pasture (RW) had the highest metabolizable protein and metabolizable energy, followed by kikuyu pasture (KP), which was significantly (p < 0.001) higher than native pastures 1 and 2 (NP1 and NP2). The highest values for effective grazing time, bite rate and BCS were found when dairy cows grazed RW followed by KP, NP2 and NP1. The results suggested that pasture type and sward height influenced grazing behaviour and BCS of dairy cows during the dry season. In the same vein, RW showed higher effective grazing time, bite rate, nutrient intake and BCS than the other three pastures suggesting that RW pastures that appear to be more expensive than native pastures could result in superior cow performance.
Background We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer ...(ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. Methods HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m.sup.2 DL0; 1,000 mg/m.sup.2 DL1) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. Results Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) greater than or equal to 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated greater than or equal to 6 months before progression. Fourteen patients reported grade greater than or equal to 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. Conclusion Pembrolizumab 200 mg and gemcitabine 1,250 mg/m.sup.2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for greater than or equal to 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. Trial registration ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively. Keywords: Pembrolizumab, Chemotherapy, HER2-negative, Advanced breast cancer, TILs, PD-L1, MDSCs
Although the importance of thermoregulation and plasticity as compensatory mechanisms for climate change has long been recognized, they have largely been studied independently. Thus, we know ...comparatively little about how they interact to shape physiological variation in natural populations. Here, we test the hypothesis that behavioral thermoregulation and thermal acclimatization interact to shape physiological phenotypes in a natural population of the diurnal lizard, Sceloporus torquatus. Every month for one year we examined thermoregulatory effectiveness and changes in the population mean in three physiological parameters: cold tolerance (Ctmin), heat tolerance (Ctmax), and the preferred body temperature (Tpref), to indirectly assess thermal acclimatization in population means. We discovered that S. torquatus is an active thermoregulator throughout the year, with body temperature varying little despite strong seasonal temperature shifts. Although we did not observe a strong signal of acclimatization in Ctmax, we did find that Ctmin shifts in parallel with nighttime temperatures throughout the year. This likely occurs, at least in part, because thermoregulation is substantially less effective at buffering organisms from selection on lower physiological limits than upper physiological limits. Active thermoregulation is effective at limiting exposure to extreme temperatures during the day, but is less effective at night, potentially contributing to greater plasticity in Ctmin than Ctmax. Importantly, however, Tpref tracked seasonal changes in temperature, which is one the factors contributing to highly effective thermoregulation throughout the year. Thus, behavior and physiological plasticity do not always operate independently, which could impact how organisms can respond to rising temperatures.
•Behavioral thermoregulation and plasticity shape physiological phenotypes.•We examined thermoregulation and plasticity in a wild lizard population.•Thermoregulation during the day potentially limits heat tolerance plasticity.•Limited thermoregulation at night potentially contributes to cold tolerance plasticity.•The preferred body temperature is labile across seasons, contributing to high thermoregulatory efficiency year-round.
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•Silicon nanowires for CO, NO, SO2 and NO2 sensing have been studied by using DFT.•Adsorption energies of gas molecules on silicon nanowires (SiNWs) were achieved.•Charge transfer ...between molecules and SiNWs were estimated by population analysis.•Electronic band structures and DOS of molecule-SiNW complexes were obtained.•The order of molecule-SiNW electronic band gaps are: NO2>SO2>CO>NO.
Silicon nanowires (SiNWs) have chemical sensitivity to molecules such as NH3 and NO2. Yet, SiNWs have not been considered for sensing harmful gases such as CO, CO2, NO, SO2, and HCN. In this work, we theoretically address the capability of SiNWs, grown along the 111 crystallographic direction and with a diameter of 1.5nm, as molecular sensors to detect these gases. The density functional theory calculations indicate that CO, NO, NO2, and SO2 molecules can be adsorbed on the SiNWs surface with energies ranging from 0.07eV to 3.41eV. However, we have also found that SiNWs are not good candidates for sensing CO2 and HCN molecules.
In recent years, there has been an increase in the descriptions of members of the lizard genus Lepidophyma. Herein, we describe a new species of Lepidophyma from the Huasteca Potosina region of ...Mexico, previously confused with L. gaigeae, from which it differs in lacking parietal spot, among other characteristics. We inferred its phylogenetic position and provide information on its thermal and hydric physiology, as well as on some other aspects of natural history. Molecular and morphological data supported the independent taxonomic status of the new species, indicating its placement as the sister taxon of L. gaigeae and a wide morphological separation between these species. Lepidophyma lusca sp. nov. has a diurnal-crepuscular activity period and occurs at lower elevations than L. gaigeae. Also, the new species differ from its sister taxon in its physiology, as reflected by its tendency toward higher thermal parameters and water loss rates. With the description of L. lusca sp. nov., the number of species in the genus Lepidophyma rises to 21.
An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes ...across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes. Our findings reveal significant taxonomic dissimilarity among biogeographical zones. Interestingly, despite this dissimilarity, species from different zones share similar higher-level phylogenetic groups and similar ecological and behavioural traits (i.e. functional traits), likely due to habitat filtering caused by perennial monoculture systems managed intensively for crop production. Honey bee species dominated orchard communities, while other managed/manageable and wild species were collected in lower numbers. Moreover, the presence of herbaceous, uncultivated open areas and organic management practices were associated with increased wild bee diversity. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic diversity, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures.
Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain “maternal-fetal ...tolerance”, SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.
El objetivo del presente estudio fue evaluar el efecto de un entrenamiento intenso en atletas de resistencia sobre el comportamiento de las colinesterasas (ChE) tras condiciones de fatiga y su ...relación con otros marcadores de carga interna. Participaron 18 atletas de sexo masculino especialistas en pruebas de resistencia. Se evaluó las ChE y dos índices de variabilidad de la frecuencia cardiaca en tres momentos diferentes, previo al protocolo (BASAL), 15 minutos posterior al protocolo (FINAL) y 24 horas después del entrenamiento (24H). Un ANOVA de una vía con post-hoc de Tukey HSD se utilizó para comparar las medias. Se encontraron cambios significativos en las variables analizadas (p < .001) con tamaños de efecto muy grandes (d > 0.9) en los diferentes momentos y correlaciones moderadas entre variables (p < .001). El comportamiento de las ChE muestra un cambio significativo (p < .001) posterior al ejercicio y una relación con otros indicadores de carga interna. Nuestros resultados indican que las ChE tienen relación con la fatiga en el caso de los deportistas estudiados, pudiendo ser una medida para determinar la carga de entrenamiento.
Purpose
Diabetes remission is a phenomenon described in the context of drastic weight loss due to bariatric surgery or low-calorie diets. Evidence suggests that increasing the intake of plant protein ...could reduce the risk of type 2 diabetes. We sought for association between changes in plant protein intake in the context of 2 healthy diets without weight loss nor glucose-lowering medication, and diabetes remission in coronary heart disease patients from the CORDIOPREV study.
Methods
Newly diagnosed type 2 diabetes participants without glucose-lowering treatment were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was assessed with a median follow-up of 60 months according to the ADA recommendation. Information on patient's dietary intake was collected using food-frequency questionnaires. At first year of intervention, 177 patients were classified according to changes in plant protein consumption into those who increased or decreased its intake, in order to perform an observational analysis on the association between protein intake and diabetes remission.
Results
Cox regression showed that patients increasing plant protein intake were more likely to remit from diabetes than those who decreased its intake (HR = 1.71(1.05–2.77)). The remission occurred mainly at first and second year of follow-up with diminished number of patients achieving remission in the third year onwards. The increase in plant protein was associated with lower intake of animal protein, cholesterol, saturated fatty acids, and fat, and with higher intake of whole grains, fibre, carbohydrates, legumes, and tree nuts.
Conclusion
These results support the need to increase protein intake of vegetal origin as dietary therapy to reverse type 2 diabetes in the context of healthy diets without weight loss.
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