Patients with genital ambiguity referred without a sex definition: the relationship between clinical picture and defined sex of rearing.

OBJECTIVE: It was to verify the association between the definition of sex of rearing and, clinical and cytogenetic features among patients with genital ambiguity referred without a sex assignment. METHODS: The sample consisted of 133 patients with genital ambiguity seen at a single reference service. These patients did not have a defined social sex at the first consultation and their etiological diagnosis was obtained during follow-up. RESULTS: A total of 133 cases were included, 74 of which were reared as males and 59 as females. No correlation was found between the year of birth and the year of the first consultation with the definition of sex of rearing. However, the definition of sex of rearing was associated with age at the first consultation, severity of genital ambiguity, presence of palpable gonad(s), presence of uterus on ultrasound, karyotype, and diagnosis. Palpable gonad(s), more virilized genitalia, absence of a uterus on ultrasound, 46, XY karyotype, or a karyotype with sex chromosome abnormalities emerged as strong predictors for defining male sex. All 77 (58 %) patients over 18 years old had a gender identity in accordance with the sex of rearing; though 9 of 77 (12 %) had homo or bisexual orientation, especially girls with Congenital Adrenal Hyperplasia. CONCLUSIONS: Clinical and cytogenetic data were strongly associated with the definition of the sex of rearing of children with genital ambiguity referred to a DSD center without sex assignment. Management in a specialized center allows the establishment of a gender identity in accordance with the sex of rearing.

Predictors for liver fibrosis in non-alcoholic patients with psoriatic diseases: A multicenter cross sectional-study.

Psoriasis has been related to metabolic dysfunction-associated fatty liver disease and, liver fibrosis. This study aimed to evaluate the prevalence of liver fibrosis in psoriasis and identify predictors for fibrosis. This is a cross-sectional study conducted from December 2012 to June 2016 assessing psoriasis and psoriatic arthritis patients attended at four centers in Mexico City. Data regarding history of the skin disease, previous and current medication, and previously diagnosed liver disease was collected. Liver fibrosis was assessed with four different non-invasive methods (FIB4, APRI, NAFLD score and elastography). We compared data based on the presence of fibrosis. Adjusted-logistic regression models were performed to estimate OR and 95% CI. A total of 160 patients were included. The prevalence of significant fibrosis using elastography was 25% (n = 40), and 7.5% (n = 12) for advanced fibrosis. Patients with fibrosis had higher prevalence of obesity (60% vs 30.8%, P = 0.04), type 2 diabetes (40% vs 27.5%, P = 0.003), gamma-glutamyl transpeptidase levels (70.8±84.4 vs. 40.1±39.2, P = 0.002), and lower platelets (210.7±58.9 vs. 242.8±49.7, P = 0.0009). Multivariate analysis showed that body mass index (OR1.11, 95%CI 1.02-1.21), type 2 diabetes (OR 3.44, 95%CI 1.2-9.88), and gamma-glutamyl transpeptidase (OR 1.01, 95%CI1-1.02) were associated with the presence of fibrosis. The use of methotrexate was not associated. Patients with psoriasis are at higher risk of fibrosis. Metabolic dysfunction, rather than solely the use of hepatotoxic drugs, likely plays a major role; it may be beneficial to consider elastography regardless of the treatment used. Metabolic factors should be assessed, and lifestyle modification should be encouraged.

Dental Stem Cells and Lipopolysaccharides: A Concise Review.

Dental tissue stem cells (DTSCs) are well known for their multipotent capacity and regenerative potential. They also play an important role in the immune response of inflammatory processes derived from caries lesions, periodontitis, and gingivitis. These oral diseases are triggered by toxins known as lipopolysaccharides (LPS) produced by gram-negative bacteria. LPS present molecular patterns associated with pathogens and are recognized by Toll-like receptors (TLRs) in dental stem cells. In this review, we describe the effect of LPS on the biological behavior of DTSCs. We also focus on the molecular sensors, signaling pathways, and emerging players participating in the interaction of DTSCs with lipopolysaccharides. Although the scientific advances generated provide an understanding of the immunomodulatory potential of DTSCs, there are still new reflections to explore with regard to their clinical application in the treatment of oral inflammatory diseases.

MicroRNAs as Diagnostic Biomarkers and Predictors of Antidepressant Response in Major Depressive Disorder: A Systematic Review.

Despite the hardships of major depressive disorder (MDD), biomarkers for the diagnosis and pharmacological management of this condition are lacking. MicroRNAs are epigenetic mechanisms that could provide promising MDD biomarkers. Our aim was to summarize the findings and provide validation for the selection and use of specific microRNAs as biomarkers in the diagnosis and treatment of MDD. A systematic review was conducted using the PubMed/Medline, Cochrane, PsycINFO, Embase, and LILACS databases from March 2022 to November 2023, with clusters of terms based on "microRNA" and "antidepressant". Studies involving human subjects, animal models, and cell cultures were included, whereas those that evaluated herbal medicines, non-pharmacological therapies, or epigenetic mechanisms other than miRNA were excluded. The review revealed differences in the expression of various microRNAs when considering the time of assessment (before or after antidepressant treatment) and the population studied. However, due to the heterogeneity of the microRNAs investigated, the limited size of the samples, and the wide variety of antidepressants used, few conclusions could be made. Despite the observed heterogeneity, the following microRNAs were determined to be important factors in MDD and the antidepressant response: mir-1202, mir-135, mir-124, and mir-16. The findings indicate the potential for the use of microRNAs as biomarkers for the diagnosis and treatment of MDD; however, more homogeneous studies are needed.

A quorum-sensing regulatory cascade for siderophore-mediated iron homeostasis in Chromobacterium violaceum.

Iron is a transition metal used as a cofactor in many biochemical reactions. In bacteria, iron homeostasis involves Fur-mediated de-repression of iron uptake systems, such as the iron-chelating compounds siderophores. In this work, we identified and characterized novel regulatory systems that control siderophores in the environmental opportunistic pathogen Chromobacterium violaceum. Screening of a 10,000-transposon mutant library for siderophore halos identified seven possible regulatory systems involved in siderophore-mediated iron homeostasis in C. violaceum. Further characterization revealed a regulatory cascade that controls siderophores involving the transcription factor VitR acting upstream of the quorum-sensing (QS) system CviIR. Mutation of the regulator VitR led to an increase in siderophore halos, and a decrease in biofilm, violacein, and protease production. We determined that these effects occurred due to VitR-dependent de-repression of vioS. Increased VioS leads to direct inhibition of the CviR regulator by protein-protein interaction. Indeed, insertion mutations in cviR and null mutations of cviI and cviR led to an increase of siderophore halos. RNA-seq of the cviI and cviR mutants revealed that CviR regulates CviI-dependent and CviI-independent regulons. Classical QS-dependent processes (violacein, proteases, and antibiotics) were activated at high cell density by both CviI and CviR. However, genes related to iron homeostasis and many other processes were regulated by CviR but not CviI, suggesting that CviR acts without its canonical CviI autoinducer. Our data revealed a complex regulatory cascade involving QS that controls siderophore-mediated iron homeostasis in C. violaceum.IMPORTANCEThe iron-chelating compounds siderophores play a major role in bacterial iron acquisition. Here, we employed a genetic screen to identify novel siderophore regulatory systems in Chromobacterium violaceum, an opportunistic human pathogen. Many mutants with increased siderophore halos had transposon insertions in genes encoding transcription factors, including a novel regulator called VitR, and CviR, the regulator of the quorum-sensing (QS) system CviIR. We found that VitR is upstream in the pathway and acts as a dedicated repressor of vioS, which encodes a direct CviR-inhibitory protein. Indeed, all QS-related phenotypes of a vitR mutant were rescued in a vitRvioS mutant. At high cell density, CviIR activated classical QS-dependent processes (violacein, proteases, and antibiotics production). However, genes related to iron homeostasis and type-III and type-VI secretion systems were regulated by CviR in a CviI- or cell density-independent manner. Our data unveil a complex regulatory cascade integrating QS and siderophores in C. violaceum.

Erythropoietin effects on cryopreserved/transplanted cat ovarian tissue: A comparison of two incubation methods.

Many feline species are currently threatened with extinction. Therefore, germplasm bank establishment has become imperative. However, cryoinjury and ischemia-reperfusion injury pose significant obstacles to both cryopreservation and xenotransplantation. In this regard, erythropoietin (Epo) represents a potential alternative strategy due to its properties. This study aimed to assess the incubation of domestic cat ovarian tissue in Epo, both before and after cryopreservation, and investigate its effectiveness in promoting revascularization following xenotransplantation. Sixteen ovaries from 8 healthy cats were sliced following elective bilateral ovariohysterectomy (OHE). Subsequently, 8 fragments measuring 3 mm³ each were obtained from the cortical region of each ovary. The fragments were allocated into 3 treatment groups: Cryo group, fragments were cryopreserved, thawed and immediately transplanted; Cryo + Epo group, fragments were first cryopreserved in nitrogen, thawed, incubated in Epo (100 IU) for 2h and transplanted; and the Epo + Cryo group, in which fragments were first incubated in Epo (100 IU) for 2h, cryopreserved, thawed and immediately transplanted. The fragments were then xenotransplanted into the dorsal subcutaneous region of ovariectomized female nude mice and retrieved at 7, 14, 21, and 28 days post-transplantation. The results indicated that Epo effectively enhanced follicular survival, preservation of viability, and tissue revascularization. The Epo + Cryo group displayed better revascularization rates on D14 and D21 post-transplantation and an increase in primordial and growing follicles on D28, the Cryo + Epo group exhibited significantly more follicles on D14 and D21, with fewer degenerated follicles.

RNA interference of NADPHcytochrome P450 increased deltamethrin susceptibility in a resistant strain of the Chagas disease vector Triatoma infestans.

The enzyme NADPH-cytochrome P450 reductase (CPR) plays a central role in cytochromes P450 activity. Gene expression analysis of cytochromes P450 and CPR in deltamethrin-resistant and susceptible populations revealed that P450s genes are involved in the development of insecticide resistance in Triatoma infestans. To clarify the role of cytochromes P450 in insecticide resistance, it was proposed to investigate the effect of CPR gene silencing by RNA interference (RNAi) in a pyrethroid resistant population of T. infestans. Silencing of the CPR gene showed a significant increase in susceptibility to deltamethrin in the population analysed. This result support the hypothesis that the metabolic process of detoxification mediated by cytochromes P450 contributes to the decreased deltamethrin susceptibility observed in the resistant strain of T. infestans.

Risk Factors Associated with Intensive Care Admission in Children with Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome (MIS-C) in Latin America: A Multicenter Observational Study of the REKAMLATINA Network.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 varies widely in its presentation and severity, with low mortality in high-income countries. In this study in 16 Latin American countries, we sought to characterize patients with MIS-C in the pediatric intensive care unit (PICU) compared with those hospitalized on the general wards and analyze the factors associated with severity, outcomes, and treatment received. Study Design: An observational ambispective cohort study was conducted including children 1 month to 18 years old in 84 hospitals from the REKAMLATINA network from January 2020 to June 2022. Results: A total of 1239 children with MIS-C were included. The median age was 6.5 years (IQR 2.5-10.1). Eighty-four percent (1043/1239) were previously healthy. Forty-eight percent (590/1239) were admitted to the PICU. These patients had more myocardial dysfunction (20% vs 4%; P < 0.01) with no difference in the frequency of coronary abnormalities (P = 0.77) when compared to general ward subjects. Of the children in the PICU, 83.4% (494/589) required vasoactive drugs, and 43.4% (256/589) invasive mechanical ventilation, due to respiratory failure and pneumonia (57% vs 32%; P = 0.01). On multivariate analysis, the factors associated with the need for PICU transfer were age over 6 years (aOR 1.76 95% CI 1.25-2.49), shock (aOR 7.06 95% CI 5.14-9.80), seizures (aOR 2.44 95% CI 1.14-5.36), thrombocytopenia (aOR 2.43 95% CI 1.77-3.34), elevated C-reactive protein (aOR 1.89 95% CI 1.29-2.79), and chest x-ray abnormalities (aOR 2.29 95% CI 1.67-3.13). The overall mortality was 4.8%. Conclusions: Children with MIS-C who have the highest risk of being admitted to a PICU in Latin American countries are those over age six, with shock, seizures, a more robust inflammatory response, and chest x-ray abnormalities. The mortality rate is five times greater when compared with high-income countries, despite a high proportion of patients receiving adequate treatment.

Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.

Affinin, Isolated from Heliopsis longipes, Induces an Antihypertensive Effect That Involves CB1 Cannabinoid Receptors and TRPA1 and TRPV1 Channel Activation.

In previous studies, we demonstrated that the ethanolic extract of Heliopsis longipes roots and its main alkamide, affinin, elicit a vasorelaxant effect through a mechanism involving activation of the gasotransmitter pathways and stimulation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels. However, it has not yet been demonstrated whether the EEH and affinin are capable of lowering high blood pressure. Therefore, the aim of the present study was to determine the effect of the oral administration of the EEH and affinin on the systolic blood pressure of NG-nitro-L-arginine methyl ester-induced hypertensive rats and to explore the participation of cannabinoid receptors and transient receptor potential channels in the mechanism of action of this alkamide. Our results showed that the ethanolic extract of H. longipes and affinin significantly lowered systolic blood pressure and induced an improvement in endothelial function, which is associated with increased serum nitric oxide levels. Inhibition of cannabinoid type 1 receptors by rimonabant (3 mg/kg), transient receptor potential ankyrin 1 channels by HC-030031 (8 mg/kg), and transient receptor potential vanilloid 1 channels by capsazepine (5 mg/kg) significantly decreased the antihypertensive effect induced by affinin, suggesting that the blood pressure-lowering effect of this alkamide involves activation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels.

Profile of lactic acid bacteria (MALDI-TOF-MS) and physico-chemical and microbiological characteristics of the raw milk and fresh artisanal cheese from Serra Geral, Minas Gerais, Brazil.

Artisanal cheese from Serra Geral, Minas Gerais, Brazil, stands out for its cultural asset and socio-economic relevance. However, standards of identity and quality and the peculiar terroir associated with the edaphoclimatic conditions have not been established. Therefore, the production flow diagram and the physico-chemical and microbiological quality of the raw milk, pingo (natural starter culture), production benches, water and fresh cheese were investigated for the first time. In addition, lactic acid bacteria (LAB) from cheese and its production environment were identified by MALDI-TOF. For that, 12 cheese making facilities were selected. The raw milk and pingo showed adequate physico-chemical characteristics for cheesemaking; however, high microbial counts were found. In the water, total and thermotolerant coliforms were also identified. The fresh cheeses were classified as 'high moisture and fat' and 'soft mass'. Most physico-chemical parameters were satisfactory; however, there were high counts of total coliforms, Staphylococcus spp. and coagulase-positive staphylococci. There were high counts of LAB in the raw milk, pingo, bench surface and fresh cheese. A total of 84 microbial biotypes from MRS agar were isolated. Lactococcus lactis was the predominant LAB, followed by Lactococcus garvieae. Leuconostoc mesenteroides (benches), Leuconostoc pseudomesenteroides (fresh cheese), and Enterococcus faecium (pingo) were identified sporadically. These results indicate the risks to public health associated with the consumption of the fresh cheese, and measures to improve its safety are needed.

The use of toxic baits for the suppression of Mediterranean fruit fly in mango orchards.

Ceratitis capitata (Wiedemann, 1824) is an insect of major economic importance in the mango orchards of the submedium of the São Francisco River Valley, the main area of mango production and exportation in Brazil. To provide alternatives for the management of C. capitata, toxic baits based on alpha-cypermethrin (Gelsura®) and spinosad (Success® 0.02 CB) were evaluated in three commercial mango experiments during two consecutive harvests: 2016/2017 (experiment 1 - area 1) and 2017/2018 (experiment 2 -area 2 and experiment 3 - area 3). According to the results, there was a large reduction in the infestation of C. capitata after five sequential applications of the alpha-cypermethrin (6 g.ha-1) and spinosad (0.38 g.ha-1) toxic baits performed at seven-day intervals during mango fruit ripening in all experiments and years (harvest) evaluated. Compared with the untreated plots, the plots with alpha-cypermethrin and spinosad applications showed a significant reduction in the damage induced (fallen fruits and/or on trees) by C. capitata. The management of C. capitata in mango orchards can include the use of the toxic bait based on alpha-cypermethrin, which represents an alternative to rotate with spinosad toxic bait in the São Francisco River Valley.

Extracorporeal Shock Wave Therapy for the Treatment of Musculoskeletal Pain: A Narrative Review.

Extracorporeal shock waves are high-intensity mechanical waves (500-1000 bar) of a microsecond duration with a morphology characterized by a rapid positive phase followed by a negative phase. BACKGROUND: Extracorporeal shock waves have been used for pain treatment for various sub-acute and chronic musculoskeletal (MSK) problems since 2000. The aim of this article is to update information on the role of extracorporeal shock wave therapy (ESWT) in the treatment of various pathologies that cause MSK pain. METHODS: Given that in the last two years, articles of interest (including systematic reviews and meta-analyses) have been published on less known indications, such as low back pain, nerve entrapments, osteoarthritis and bone vascular diseases, a literature search was conducted in PubMed, the Cochrane Database, EMBASE, CINAHL and PEDro, with the aim of developing a narrative review of the current literature on this topic. The purposes of the review were to review possible new mechanisms of action, update the level of evidence for known indications and assess possible new indications that have emerged in recent years. RESULTS: Although extracorporeal shock waves have mechanical effects, their main mechanism of action is biological, through a phenomenon called mechanotransduction. There is solid evidence that supports their use to improve pain in many MSK pathologies, such as different tendinopathies (epicondylar, trochanteric, patellar, Achilles or calcific shoulder), plantar fasciitis, axial pain (myofascial, lumbar or coccygodynia), osteoarthritis and bone lesions (delayed union, osteonecrosis of the femoral head, Kienbock's disease, bone marrow edema syndrome of the hip, pubis osteitis or carpal tunnel syndrome). Of the clinical indications mentioned in this review, five have a level of evidence of 1+, eight have a level of evidence of 1-, one indication has a level of evidence of 2- and two indications have a level of evidence of 3. CONCLUSIONS: The current literature shows that ESWT is a safe treatment, with hardly any adverse effects reported. Furthermore, it can be used alone or in conjunction with other physical therapies such as eccentric strengthening exercises or static stretching, which can enhance its therapeutic effect.

Solid-State Fermented Pineapple Peel: A Novel Food Ingredient with Antioxidant and Anti-Inflammatory Properties.

It has been reported that pineapple (Ananas comosus) contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. However, a substantial amount of pineapple residue is produced due to a lack of valorization applications at the industrial scale, resulting in the loss of valuable nutrients. Solid-state fermentation (SSF) is proposed as an innovative strategy to enhance the release of bound phenolics from pineapple residues. In this work, the effects of SSF of pineapple peels with Lactobacillus plantarum, Lactobacillus rhamnosus, and Aspergillus oryzae on the release of phenolic compounds and their antioxidant and anti-inflammatory activities were evaluated, respectively. Pineapple peel extracts after SSF showed an increase in the release of phenolic compounds (248.11% with L. plantarum, 182% with A. oryzae, and 180.10% with L. rhamnosus), which led to an increase in the cellular antioxidant (81.94% with L. rhamnosus) and anti-inflammatory potential (nitric oxide inhibition of 62% with L. rhamnosus) compared to non-fermented extracts. Therefore, SSF of pineapple peels with L. plantarum, L. rhamnosus, and A. oryzae thrives as a new approach for the production of secondary metabolites with remarkable biological benefits, which can be the precursors for novel biofortified and nutraceutical-enriched foods that meet the needs of the most demanding and health-conscious consumers.

The DEAD-box RNA helicase RhlB is required for efficient RNA processing at low temperature in Caulobacter.

IMPORTANCE: One of the most important control points in gene regulation is RNA stability, which determines the half-life of a transcript from its transcription until its degradation. Bacteria have evolved a sophisticated multi-enzymatic complex, the RNA degradosome, which is dedicated mostly to RNA turnover. The combined activity of RNase E and the other RNA degradosome enzymes provides an efficient pipeline for the complete degradation of RNAs. The DEAD-box RNA helicases are very often found in RNA degradosomes from phylogenetically distant bacteria, confirming their importance in unwinding structured RNA for subsequent degradation. This work showed that the absence of the RNA helicase RhlB in the free-living Alphaproteobacterium Caulobacter crescentus causes important changes in gene expression and cell physiology. These are probably due, at least in part, to inefficient RNA processing by the RNA degradosome, particularly at low-temperature conditions.

Glycemic and Satiety Response to Three Mexican Honey Varieties.

Honey is considered one of the last untreated natural food substances, with a complex composition. It is produced by bees (Apis mellifera) from nectar. The glycemic index (GI) is a physiological assessment of a food's carbohydrate content via its effect on postprandial blood glucose concentrations. This study evaluated the GI and the satiety response to three Mexican types of honey administered to 26 healthy volunteers. The fructose values ranged from 272.40 g/kg to 395.10 g/kg, while the glucose value ranged from 232.20 g/kg to 355.50 g/kg. The fructose/glucose (F/G) ratio of honey was 1.45, 1.00, and 1.17 for highland, multifloral, and avocado honey, respectively. Highland and avocado honey were classified as medium-GI (69.20 ± 4.07 and 66.36 ± 5.74, respectively), while multifloral honey was classified as high-GI (74.24 ± 5.98). Highland honey presented a higher satiety values response than glucose. The difference in GI values and the satiety response effect of highland honey could be explained by its different carbohydrate composition and the possible presence of other honey components such as phytochemicals. Honey, especially avocado, could therefore be used as a sweetener without altering significantly the blood glucose concentration.

Oncogenic Ras and ΔNp63α cooperate to recruit immunosuppressive polymorphonuclear myeloid-derived suppressor cells in a mouse model of squamous cancer pathogenesis.

Introduction: Amplification of human chromosome 3q26-29, which encodes oncoprotein ΔNp63 among other isoforms of the p63 family, is a feature common to squamous cell carcinomas (SCCs) of multiple tissue origins. Along with overexpression of ΔNp63, activation of the protooncogene, RAS, whether by overexpression or oncogenic mutation, is frequently observed in many cancers. In this study, analysis of transcriptome data from The Cancer Genome Atlas (TCGA) demonstrated that expression of TP63 mRNA, particularly ΔNp63 isoforms, and HRAS are significantly elevated in advanced squamous cell carcinomas of the head and neck (HNSCCs), suggesting pathological significance. However, how co-overexpressed ΔNp63 and HRAS affect the immunosuppressive tumor microenvironment (TME) is incompletely understood. Methods: Here, we established and characterized an immune competent mouse model using primary keratinocytes with retroviral-mediated overexpression of ΔNp63α and constitutively activated HRAS (v-rasHa G12R) to evaluate the role of these oncogenes in the immune TME. Results: In this model, orthotopic grafting of wildtype syngeneic keratinocytes expressing both v-rasHa and elevated levels of ΔNp63α consistently yield carcinomas in syngeneic hosts, while cells expressing v-rasHa alone yield predominantly papillomas. We found that polymorphonuclear (PMN) myeloid cells, experimentally validated to be immunosuppressive and thus representing myeloid-derived suppressor cells (PMN-MDSCs), were significantly recruited into the TME of carcinomas arising early following orthotopic grafting of ΔNp63α/v-rasHa-expressing keratinocytes. ΔNp63α/v-rasHa-driven carcinomas expressed higher levels of chemokines implicated in recruitment of MDSCs compared to v-rasHa-initiated tumors, providing a heretofore undescribed link between ΔNp63α/HRAS-driven carcinomas and the development of an immunosuppressive TME. Conclusion: These results support the utilization of a genetic carcinogenesis model harboring specific genomic drivers of malignancy to study mechanisms underlying the development of local immunosuppression.

New frontiers of soil fungal microbiome and its application for biotechnology in agriculture.

The fungi-based technology provided encouraging scenarios in the transition from a conventionally based economic system to the potential security of sources closely associated with the agricultural sphere such as the agriculture. In recent years, the intensification of fungi-based processes has generated significant gains, additionally to the production of materials with significant benefits and strong environmental importance. Furthermore, the growing concern for human health, especially in the agriculture scenario, has fostered the investigation of organisms with high biological and beneficial potential for use in agricultural systems. Accordingly, this study offered a comprehensive review of the diversity of the soil fungal microbiome and its main applications in a biotechnological approach aimed at agriculture and food chain-related areas. Moreover, the spectrum of opportunities and the extensive optimization platform for obtaining fungi compounds and metabolites are discussed. Finally, future perspectives regarding the insurgency of innovations and challenges on the broad rise of visionary solutions applied to the biotechnology context are provided.

Nutritional assessment of nixtamalized maize tortillas produced from dry masa flour, landraces, and high yield hybrids and varieties.

In the scientific literature there are different analyses of the nutritional profiles of maize tortillas, whether they are landraces or hybrid maize versus those made with dry masa flour (DMF). In general terms, there is agreement in the reported content of moisture. However, for the other nutrients, a great disparity is reported for each type of tortilla which may be due to various factors such as the type of maize or processing methods. In this study, the nutritional aspects of maize tortillas made with different genotypes (five hybrids, two varieties, five landraces, six hybrid mixtures and six dry masa flours) under controlled conditions, were compared. More than 30 characteristics were analyzed. High performance hybrids and varieties (HPHV) and landraces had the highest (p < 0.05) antioxidant capacity (58.8% free, 150.2% bound). In terms of vitamins contents, the tortillas produced from DMF contained 11.2 and 3.5 times more B1, 18.6 and 7.8 times more B2, and 2.7 and 5.3 times more B3 than HPHV and landraces respectively; and only in these samples was detected folic acid. DMF tortilla samples contained 1.75 times more sodium and 2.75 times more iron than the other groups, and 0.75 times less calcium than HPHV. Zinc was present in higher concentration (p < 0.05) in DMF tortilla samples. The landraces had the highest protein content (average 10.28%), but the tortillas produced from DMF presented the highest protein quality evaluated by protein digestibility-corrected amino acid score (PDCAAS) (p < 0.05) that represents 27, 25 and 19% more than hybrids mixture, HPHV and landraces, respectively. This work gives valuable information on how different types of grains differ in the nutritional quality affecting the final product to provide more elements in the decision-making of processors. There is no a perfect maize, but there are genotypes that can be combined as mixtures and the processing method to design superior nutritional tortillas and related products for populations that highly consume them and improve their human health.

Disposable electrochemical platform based on solid-binding peptides and carbon nanomaterials: an alternative device for leishmaniasis detection.

Neglected tropical diseases are those caused by infectious agents or parasites and are considered endemic in low-income populations. These diseases also have unacceptable indicators and low investment in research, drug production, and control. Tropical diseases such as leishmaniasis are some of the main causes of morbidity and mortality around the globe. Electrochemical immunosensors are promising tools for diagnostics against these diseases. One such benefit is the possibility of assisting diagnosis in isolated regions, where laboratory infrastructure is lacking. In this work, different peptides were investigated to detect antibodies against Leishmania in human and canine serum samples. The peptides evaluated (395-KKG and 395-G) have the same recognition site but differ on their solid-binding domains, which ensure affinity to spontaneously bind to either graphene oxide (GO) or graphene quantum dots (GQD). Cyclic voltammetry and differential pulse voltammetry were employed to investigate the electrochemical behavior of each assembly step and the role of each solid-binding domain coupled to its anchoring material. The graphene affinity peptide (395-G) showed better reproducibility and selectivity when coupled to GQD. Under the optimized set of experimental conditions, negative and positive human serum samples responses were distinguished based on a cut-off value of 82.5% at a 95% confidence level. The immunosensor showed selective behavior to antibodies against Mycobacterium leprae and Mycobacterium tuberculosis, which are similar antibodies and potentially sources of false positive tests. Therefore, the use of the graphene affinity peptide as a recognition site achieved outstanding performance for the detection of Leishmania antibodies.