Intestinal Dysbiosis: Exploring Definition, Associated Symptoms, and Perspectives for a Comprehensive Understanding - a Scoping Review.

Dysbiosis is a clinical condition marked by altered gut microbiota resulting from external and internal host factors. It is strongly associated with gastrointestinal and extraintestinal alterations, so its symptomatology is broad and nonspecific. To date, gaps remain that limit professionals from making a timely diagnosis and prescribing the appropriate treatment. We aim to synthesize existing literature regarding clinical parameters for the early detection of patients with intestinal dysbiosis and the clinical events in which the use of probiotics as adjuvant therapy is most frequently reported. A scoping review of the literature was conducted in PubMed, Embase, Cochrane, and BVS (Biblioteca Virtual en Salud in Spanish) databases for articles published in the last 5 years. Primary studies and literature reviews related to clinical presentation, dysbiosis screening, and probiotics as adjuvant therapy for adult and pediatric patients were included. Twenty-three articles were retrieved in which the most frequently reported symptoms were abdominal distension, abdominal pain, and diarrhea. Chronic and metabolic diseases where the conditions most strongly associated with dysbiosis. Depending on symptomatology and etiology, dysbiosis is often treated with probiotics. Dysbiosis, often linked to diarrhea, should be considered with other symptoms like abdominal distension and pain, along with predisposing conditions and patient risk factors. Probiotics are commonly used as co-adjuvant treatments for antibiotic-associated diarrhea, irritable bowel syndrome, and childhood allergic diseases. The most commonly used probiotics were Weizmannia coagulans (formerly B. coagulans), Alkalihalobacillus clausii (formerly Bacillus clausii), Lacticaseibacillus rhamnosus, Limosilactobacillus reuteri, and Saccharomyces boulardii.

Diagnostic potential of combining plasma biomarkers of tissue damage and inflammation in pediatric TB.

INTRODUCTION: Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children. METHODS: We analyzed 17 biomarkers in 15 non-M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead-based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups. RESULTS: Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non-MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p < 0.001) and a significant correlation between IL-2 and IL-1ra (r = 0.92), IL-21 (r = 0.91), MCP-3 (r = 0.84), and MMP-1 (r = 0.85). The IFN-γ/MCP-1 ratio was the most accurate biomarker combination for differentiating between MTB-infected and non-MTB-infected children (AUC, 0.82; sensitivity, 87.9%; specificity, 66.6%; p < 0.001) and between active TB and non-MTB-infected children (AUC 0.82; sensitivity 88.0%; specificity 60.0%; p < 0.001). None of the biomarkers investigated were able to discriminate between LTBI and active TB. CONCLUSION: Our data suggest that combining the analyses of multiple biomarkers in plasma has the potential to enhance diagnosis of TB in children and, thus, warrants additional investigation. In particular, the diagnostic potential of IFN-γ/MCP-1 ratios should be further explored in larger pediatric cohorts.

Impact of genetic variants in the solute carrier (SLC) genes encoding drug uptake transporters on the response to anticancer chemotherapy.

Cancer drug resistance constitutes a severe limitation for the satisfactory outcome of these patients. This is a complex problem due to the co-existence in cancer cells of multiple and synergistic mechanisms of chemoresistance (MOC). These mechanisms are accounted for by the expression of a set of genes included in the so-called resistome, whose effectiveness often leads to a lack of response to pharmacological treatment. Additionally, genetic variants affecting these genes further increase the complexity of the question. This review focuses on a set of genes encoding members of the transportome involved in drug uptake, which have been classified into the MOC-1A subgroup of the resistome. These proteins belong to the solute carrier (SLC) superfamily. More precisely, we have considered here several members of families SLC2, SLC7, SLC19, SLC22, SLCO, SLC28, SLC29, SLC31, SLC46, and SLC47 due to the impact of their expression and genetic variants in anticancer drug uptake by tumor cells or, in some cases, general bioavailability. Changes in their expression levels and the appearance of genetic variants can contribute to the Darwinian selection of more resistant clones and, hence, to the development of a more malignant phenotype. Accordingly, to address this issue in future personalized medicine, it is necessary to characterize both changes in resistome genes that can affect their function. It is also essential to consider the time-dependent dimension of these features, as the genetic expression and the appearance of genetic variants can change during tumor progression and in response to treatment.

Secretome Analysis Using Affinity Proteomics and Immunoassays: A Focus on Tumor Biology.

The study of the cellular secretome using proteomic techniques continues to capture the attention of the research community across a broad range of topics in biomedical research. Due to their untargeted nature, independence from the model system used, historically superior depth of analysis, as well as comparative affordability, mass spectrometry-based approaches traditionally dominate such analyses. More recently, however, affinity-based proteomic assays have massively gained in analytical depth, which together with their high sensitivity, dynamic range coverage as well as high throughput capabilities render them exquisitely suited to secretome analysis. In this review, we revisit the analytical challenges implied by secretomics and provide an overview of affinity-based proteomic platforms currently available for such analyses, using the study of the tumor secretome as an example for basic and translational research.

Unveiling the impact of circulating tumor cells: Two decades of discovery and clinical advancements in solid tumors.

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required. CTCs serve as versatile biomarkers, offering insights into tumor biology, metastatic progression, and treatment response. This review summarizes the latest advancements in CTC research and highlights future directions of investigation. Special attention is given to concurrent evaluations of CTCs and other circulating biomarkers, particularly circulating tumor DNA. Multi-analyte assessment holds the potential to unlock the full clinical capabilities of liquid biopsy. In conclusion, CTCs represent a transformative biomarker in precision oncology, offering extraordinary opportunities to translate scientific discoveries into tangible improvements in patient care.

Moderate Aerobic Exercise Induces Homeostatic IgA Generation in Senile Mice.

A T-cell-independent (TI) pathway activated by microbiota results in the generation of low-affinity homeostatic IgA with a critical role in intestinal homeostasis. Moderate aerobic exercise (MAE) provides a beneficial impact on intestinal immunity, but the action of MAE on TI-IgA generation under senescence conditions is unknown. This study aimed to determine the effects of long-term MAE on TI-IgA production in young (3 month old) BALB/c mice exercised until adulthood (6 months) or aging (24 months). Lamina propria (LP) from the small intestine was obtained to determine B cell and plasma cell sub-populations by flow cytometry and molecular factors related to class switch recombination [Thymic Stromal Lymphopoietin (TSLP), A Proliferation-Inducing Ligand (APRIL), B Cell Activating Factor (BAFF), inducible nitric oxide synthase (iNOS), and retinal dehydrogenase (RDH)] and the synthesis of IgA [α-chain, interleukin (IL)-6, IL-21, and Growth Factor-ß (TGF-ß)]; and epithelial cells evaluated IgA transitosis [polymeric immunoglobulin receptor (pIgR), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-4] by the RT-qPCR technique. The results were compared with data obtained from sedentary age-matched mice. Statistical analysis was computed with ANOVA, and p < 0.05 was considered to be a statistically significant difference. Under senescence conditions, MAE promoted the B cell and IgA+ B cells and APRIL, which may improve the intestinal response and ameliorate the inflammatory environment associated presumably with the downmodulation of pro-inflammatory mediators involved in the upmodulation of pIgR expression. Data suggested that MAE improved IgA and downmodulate the cytokine pro-inflammatory expression favoring homeostatic conditions in aging.

Genotypic and phenotypic characterisation of a nosocomial outbreak of Candida auris in Spain during 5 years.

OBJECTIVES: The investigation of Candida auris outbreaks is needed to provide insights into its population structure and transmission dynamics. We genotypically and phenotypically characterised a C. auris nosocomial outbreak occurred in Consorcio Hospital General Universitario de Valencia (CHGUV), Spain. METHODS: Data and isolates were collected from CHGUV from September 2017 (first case) until September 2021. Thirty-five isolates, including one from an environmental source, were randomly selected for whole genome sequencing (WGS), and the genomes were analysed along with a database with 335 publicly available genomes, assigning them to one of the five major clades. In order to identify polymorphisms associated with drug resistance, we used the fully susceptible GCA_003014415.1 strain as reference sequence. Known mutations in genes ERG11 and FKS1 conferring resistance to fluconazole and echinocandins, respectively, were investigated. Isolates were classified into aggregating or non-aggregating. RESULTS: All isolates belonged to clade III and were from an outbreak with a single origin. They clustered close to three publicly available genomes from a hospital from where the first patient was transferred, being the probable origin. The mutation VF125AL in the ERG11 gene, conferring resistance to fluconazole, was present in all the isolates and one isolate also carried the mutation S639Y in the FKS1 gene. All the isolates had a non-aggregating phenotype (potentially more virulent). CONCLUSIONS: Isolates are genotypically related and phenotypically identical but one with resistance to echinocandins, which seems to indicate that they all belong to an outbreak originated from a single isolate, remaining largely invariable over the years. This result stresses the importance of implementing infection control practices as soon as the first case is detected or when a patient is transferred from a setting with known cases.

How Does Nerve Mechanical Interface Treatment Impact Pre-Surgical Carpal Tunnel Syndrome Patients? A Randomized Controlled Trial.

BACKGROUND: Carpal tunnel syndrome (CTS) presents a high burden on the healthcare system. However, no alternative treatments are provided during the waiting period. In addition, the incidence of severe patients with comorbidities is underestimated. The aim of this study was to determine whether nerve mechanical interface treatment improves the symptoms, function, and quality of life in pre-surgical CTS patients. METHODS: A randomized controlled trial and intention-to-treat analysis were carried out. Forty-two patients with an electrodiagnosis of carpal tunnel syndrome, included on the surgery waiting list of a public healthcare system, were analyzed. The intervention group (n = 20) received a 45 min session/per week of instrument-assisted manual therapy (diacutaneous fibrolysis) for 3 weeks. The Boston Carpal Tunnel Questionnaire (BCTQ) was the primary outcome. The symptoms, mechanical threshold, grip strength, mechanosensitivity of the median nerve, quality of life, and patient satisfaction were included as secondary outcomes. The control group (n = 22) remained on the waiting list. RESULTS: The intervention seems to be beneficial for the BCTQ score (function and symptoms scale), pain, and mechanosensitivity after treatment, at the 3 and 6 months follow-up (p < 0.05). Kinesiophobia was improved at 6 months (p = 0.043; η2 = 0.10) and the mechanical threshold at the 3-month follow-up (p = 0.048; η2 = 0.10). No differences were identified for grip strength. At 6 months, the intervention group patients were satisfied (100%), as opposed to the controls, who felt that they had experienced a worsening of their condition (50.1%). CONCLUSIONS: Nerve mechanical interface treatment improved the symptoms, function, and quality of life in pre-surgical CTS patients. One hundred percent of the treated patients, characterized as moderate and severe CTS with associated comorbidities, were satisfied.

Eculizumab as Salvage Treatment for Thrombotic Microangiopathy After Lung Transplantation.

BACKGROUND: Thrombotic microangiopathy (TMA) is a rare complication after lung transplantation (LT) that has seldom been characterized in detail. Recent evidence has linked TMA other than primary atypical hemolytic uremic syndrome (aHUS) with hyperactivation of the complement alternative pathway. The focus of this investigation was to analyze the treatment response with eculizumab in TMA after LT. METHODS: Case series where we have studied 11 patients with TMA after LT from 2 Spanish tertiary healthcare centers. Clinical data and response rates to eculizumab are provided. RESULTS: The main indication for lung transplant was chronic obstructive pulmonary disease (COPD) (36%) and most cases (82%) received bilateral LT. The median time to TMA diagnosis was 11.6 months (4.7-28.9) and the TMA trigger in the majority of cases (73%) was immunosuppressive drugs. Platelet and hemoglobin nadir were 58 × 103/µL (24-108) and 7.7 g/dL (7.1-7.9), respectively. All cases presented acute kidney injury (AKI) with a median creatinine of 4 mg/dL (3.2-4.8) and 54.5% required acute dialysis. Eculizumab was started after a median time of 8 days (6-14) with a median duration of 3 weeks (2-8). Complete TMA response was observed in 7 (63.6%) cases and hematologic response in 10 (90.9%). The time to hematologic and renal response was 23 days (13-29) and 28 days (14-46), respectively. CONCLUSIONS: TMA after LT is infrequent but potentially devastating. Our findings suggest that short cycles of eculizumab may be effective for severe TMA after LT.

The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease.

Early diagnosis and treatment of chronic kidney disease (CKD) is a worldwide challenge. Subjects with albumin-to-creatinine ratio (ACR) ≥ 30 mg/g and preserved renal function are considered to be at no cardiorenal risk in clinical practice, but prospective clinical studies evidence increased risk, even at the high-normal (HN) ACR range (10-30 mg/g), supporting the need to identify other molecular indicators for early assessment of patients at higher risk. Following our previous studies, here we aim to stratify the normoalbuminuria range according to cardiorenal risk and identify the glycoproteins and N-glycosylation sites associated with kidney damage in subclinical CKD. Glycoproteins were analyzed in urine from hypertensive patients within the HN ACR range compared to control group (C; ACR < 10 mg/g) by mass spectrometry. A different cohort was analyzed for confirmation (ELISA) and sex perspective was evaluated. Patients' follow-up for 8 years since basal urine collection revealed higher renal function decline and ACR progression for HN patients. Differential N-glycopeptides and their N -glycosylation sites were also identified, together with their pathogenicity. N-glycosylation may condition pathological protein deregulation, and a panel of 62 glycoproteins evidenced alteration in normoalbuminuric subjects within the HN range. Haptoglobin-related protein, haptoglobin, afamin, transferrin, and immunoglobulin heavy constant gamma 1 (IGHG1) and 2 (IGHG2) showed increased levels in HN patients, pointing to disturbed iron metabolism and tubular reabsorption and supporting the tubule as a target of interest in the early progression of CKD. When analyzed separately, haptoglobin, afamin, transferrin, and IGHG2 remained significant in HN, in both women and men. At the peptide level, 172 N-glycopeptides showed differential abundance in HN patients, and 26 showed high pathogenicity, 10 of them belonging to glycoproteins that do not show variation between HN and C groups. This study highlights the value of glycosylation in subjects not meeting KDIGO criteria for CKD. The identified N-glycopeptides and glycosylation sites showed novel targets, for both the early assessment of individual cardiorenal risk and for intervention aimed at anticipating CKD progression.

The systemic cellular immune response against allogeneic mesenchymal stem cells is influenced by inflammation, differentiation and MHC compatibility: in vivo study in the horse.

The effectiveness and safety of allogeneic mesenchymal stem/stromal cells (MSCs) can be affected by patient's immune recognition. Thus, MSC immunogenicity and their immunomodulatory properties are crucial aspects for therapy. Immune responses after allogeneic MSC administration have been reported in different species, including equine. Interactions of allogenic MSCs with the recipient's immune system can be influenced by factors like matching or mismatching for the major histocompatibility complex (MHC) between donor-recipient, and by the levels of MHC expression in MSCs. The latter can vary upon MSC inflammatory exposure or differentiation, such as chondrogenic induction, making both priming and differentiation interesting therapeutic strategies. This study investigated the systemic in vivo immune cellular response against allogeneic equine MSCs in these situations. Either MSCs in basal conditions (MSC-naïve), pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were repeatedly administered subcutaneously into autologous, MHC-matched or MHC-mismatched allogeneic equine recipients. At different time-points after each administration, lymphocytes were obtained from recipient horses and exposed in vitro to the same type of MSCs to assess the proliferative response of different T cell subsets (cytotoxic, helper, regulatory), B cells, and interferon gamma (IFNγ) secretion. Higher proliferative response of helper and cytotoxic T lymphocytes and IFNγ secretion was observed in response to all types of MHC-mismatched MSCs over MHC-matched ones. MSC-primed produced the highest immune response, followed by MSC-naïve, and MSC-chondro. However, MSC-primed activated Treg and had a mild effect on B cells, and the response after their second administration was similar to the first one. On the other hand, both MSC-chondro and MSC-naïve barely induced Treg response but promoted B lymphocyte activation, and proportionally induced a higher cell response after the second administration. In conclusion, both the type of MSC conditioning and the MHC compatibility influenced systemic immune recognition of equine MSCs after single and repeated administrations, but the response was different. Selecting MHC-matched donors would be particularly recommended for MSC-primed and repeated MSC-naïve administrations. While MHC-mismatching in MSC-chondro would be less critical, B cell response should not be ignored. Comprehensively investigating the in vivo immune response against equine allogeneic MSCs is crucial for advancing veterinary cell therapies.

Effect of chronic stress on gel-forming mucins in the small intestine of BALB/c mice.

Intestinal homeostasis involves the collaboration of gut barrier components, such as goblet cells and IgA-microbiota complexes, that are under the control of stress that promotes inflammatory responses addressed primarily in the colon. The aim of this study was to evaluate the effect of stress on mucins, goblet cells, and proinflammatory parameters in the proximal and distal regions of the small intestine. A group (n = 6) of female 8-week-old BALB/c mice underwent board immobilization stress (2 h per day for 4 days) and were sacrificed with isoflurane. Samples from proximal and distal small segments were collected to analyze the following: 1) goblet cells stained with periodic acid-Schiff (PAS) and with alcian blue (AB) to visualize histologically neutral and acidic mucins, respectively; 2) IgA-microbiota complexes identified by flow cytometry in intestinal lavages; and 3) MUC2, MUC5AC, and IL-18 mRNA levels in whole mucosal scrapings by reverse transcription-qPCR. Regarding the unstressed group, in the proximal region of small intestine both PAS+ and AB+ goblet cells were unchanged; however, MUC5AC and IL-18 mRNA levels were increased, and the percentage of IgA-microbiota complexes was reduced. In the distal segment, the number of PAS+ goblet cells was increased, whereas the number of AB+ goblet cells was reduced and did not affect the remaining parameters. The data suggest that stress induces inflammation in the proximal small intestine; these findings may provide an experimental reference for human diseases that may affect the proximal small intestine, such as Crohn's disease, in which stress contributes to the progression of intestinal inflammation or relapse.

Wave Impedance Determination for PCB SIWs Considering Metal Roughness Loss Effects.

This paper presents an expression to determine the complex wave impedance of a substrate-integrated waveguide for the dominant TE10 propagation mode, notably enhancing the accuracy in modeling the corresponding imaginary part. This was accomplished by systematically identifying the need to consider additional conductor losses caused by the interaction of the propagating fields with the conductor material. In fact, by using the proposed expression, the complex impedance can straightforwardly be determined by combining propagation constant data, and the resistance that represents the loss associated with longitudinal currents occurring at the top and bottom walls, which are influenced by the conductor surface roughness. This allows for completely describing the characteristics of the waveguide when assuming uniform propagation along its length. Furthermore, since the voltage-current, the power-current, and the power-voltage impedances can easily be obtained from the wave impedance, the proposal enables representing the matching characteristics of the waveguide for circuit design purposes. An agreement between simulated and experimental insertion loss is achieved for substrate-integrated waveguides of two different widths when reconstructing the corresponding S-parameters using the determined wave impedance.

Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Understanding the Mechanosensitivity of the Median Nerve in Pre-Surgical Carpal Tunnel Syndrome Patients: A Correlational Study.

(1) Background: Neurodynamic tests are recommended for the diagnosis of entrapment neuropathies such as carpal tunnel syndrome (CTS). However, their association with clinical variables in severe patients or patients with associated comorbidities is poorly documented. This study aims to analyze the association between the mechanosensitivity of the median nerve and symptoms, function and psycho-social variables in moderate and severe carpal tunnel syndrome patients with comorbidities; (2) Methods: Correlational study. In total, 42 pre-surgical patients (24 females; 59.1 ± 12.7 years) included in the Spanish Public Healthcare System with an electrodiagnostic of CTS were selected. Sociodemographic variables and clinical features (symptoms, function, sensitivity and quality of life evaluated with the 36-item Short Form Survey (SF-36) and the Medical Outcomes Study Sleep Scale (MOS-sleep) were recorded. Upper Limb Neurodynamic Test 1 was used to evaluate neural mechanosensitivity; (3) Results: The 81% had a severe CTS and 78.6% had some comorbidity. The average time from the first medical visit to the surgeon's visit was 365.5 days. Median nerve mechanosensitivity correlated weakly with the SF-36 subscale, General Health, (Spearman's rho = 0.367) and MOS sleep scale, Awaken Short of Breath or with headache dimension (Spearman's rho = -0.353) and moderately with SF-36 subscale, Social Functioning (Spearman's rho = 0.553); (4) Conclusions: No associations were observed for median nerve mechanosensitivity, except for quality of life and sleep. Both social determinants and clinical variables should be considered when examining and treating these patients.

Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU.

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

Outcome of stress on G protein-coupled receptors and hypoxia inducible factor-1α.

Stress drives neuroendocrine signals with detrimental effects to the intestinal homeostasis. The aim of this study was to evaluate the effect of stress on intestinal hypoxia response elements, including G protein-coupled receptor 41 (GPR41), GPR43, and hypoxia inducible factor (HIF)-1α. Groups of five BALB/c mice were subjected to acute (2 h per day) and chronic (2 h per day for 4 days) stress induced by restraint, and the results were compared to those of an unstressed control group. Whole mucosal samples from the colon were collected to evaluate the expression of GPR41, GPR43 and HIF-1α using Western blot chemiluminescent analysis. Compared to the control group, in the chronic stress group the expression of GPR43 (P = 0.0092) and HIF-1α (P < 0.0001) were significantly lower and the expression of GPR41 was similar (P = 0.9184); acute stress significantly increased HIF-1α expression (P = 0.0030) and increased GPR41 expression (P = 0.0937), without affecting GPR43 (P = 0.9184). These findings offer insights into the modulation of hypoxia response elements under stress conditions and their pharmacological implications for developing drugs that mitigate the effects of stress on intestinal homeostasis.

Preharvest Elicitors as a Tool to Enhance Bioactive Compounds and Quality of Both Peel and Pulp of Yellow Pitahaya (Selenicereus megalanthus Haw.) at Harvest and during Postharvest Storage.

Yellow pitahaya is a tropical fruit that has gained popularity in recent years. Natural elicitors are compounds that can stimulate the resistance and quality of fruits. The objective of this study was to evaluate the effects of natural elicitors, methyl salicylate (MeSa), methyl jasmonate (JaMe), salicylic acid (SA) and oxalic acid (OA) at concentrations of 0.1 mM (MeSa and JaMe) and 5 mM (SA and OA), applied to the yellow pitahaya fruits under greenhouse conditions. After full blossom, four applications were made with a frequency of 15 days. At the time of harvest and after storage, the following variables were evaluated: firmness (whole fruit), total soluble solids (TSS), total acidity (TA), phenolics and carotenoids (in the pulp), while phenolics, carotenoids, macronutrients and micronutrients were determined in the peel. The results showed MeSa advanced the fruit maturation, according to higher TSS, lower TA and firmness than MeJa-treated fruits, for which a delayed ripening process was shown. All treatments induced a higher polyphenolic concentration during storage. Regarding the alternative use of the peel as a by-product, the application of natural elicitors significantly increased the content of polyphenols, carotenoids, macronutrients and micronutrients in the peel, especially MeSa, which can be used as a bioactive compound in the food industry. In conclusion, the results indicate that natural elicitors can be an alternative to improve the quality and shelf life of yellow pitahaya fruits.

Are physical activity and/or adherence to the Mediterranean diet determinants of the changes found in kinanthropometric variables, body composition and physical fitness in adolescents?

The practice of physical activity and adherence to the Mediterranean diet (AMD) have been extensively studied for their relationship with kinanthropometric, body composition and physical fitness variables. However, no previous study has analyzed whether these healthy habits are equally determinant for the differences found in kinanthropometric, body composition and physical fitness variables or, on the contrary, if one of them is more relevant. For this reason, the objectives of the present study were: (1) to analyze the differences in kinanthropometric, body composition, and physical fitness variables between adolescents with different levels of physical activity and AMD, and (2) to determine whether physical activity and/or AMD are predictors of differences in kinanthropometric variables, body composition or physical fitness in adolescents. The sample consisted of 791 adolescents (404 males and 387 females; mean age: 14.39±1.26 year-old) whose physical activity level, AMD, kinanthropometric variables, body composition and physical fitness, were measured. The results showed differences when considering the level of physical activity in kinanthropometric variables, body composition and physical fitness, but not the level of AMD, which was relevant only when it was poor, and the adolescents were inactive. Nevertheless, the AMD did not seem to exert such a determining effect as to produce significant differences on its own. On the other hand, the practice of physical activity did act as a predictor mainly of changes in the fitness variables. Therefore, the main novelty of the present study is the establishment of an order of importance of the healthy habits acquired by adolescents, concluding that the practice of physical activity is more determinant for the differences found in the study variables.