PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico.

BACKGROUND: Basal cell carcinoma (BCC) represents about 80% of all cases of skin cancer. The PTCH1 is a transmembrane protein of the Sonic Hedgehog signaling pathway that regulates cell proliferation. Genetic variants in PTCH1 gene have been previously described in association with BCC development. In addition, PTCH1 mRNA and protein expression analysis are also significant to understand its role in skin cancer physiopathology. METHODS: An analytical cross-sectional study was performed, and a total of 250 BCC patients and 290 subjects from the control group (CG) were included, all born in western Mexico. The genotypes and relative expression of the mRNA were determined by TaqMan® assay. The protein expression was investigated in 70 BCC paraffin-embedded samples with PTCH1 antibodies. Semi-quantitative analysis was performed to determine the expression level in the immunostained cells. RESULTS: We did not find evidence of an association between PTCH1 rs357564, rs2297086, rs2236405, and rs41313327 genetic variants and susceptibility to BCC. Likewise, no statistically significant differences were found in the comparison of the mRNA level expression between BCC and CG (p > 0.05). The PTCH1 protein showed a low expression in 6 of the analyzed samples and moderate expression in 1 sample. No association was found between genetic variants, protein expression, and demographic-clinical characteristics (p > 0.05). CONCLUSION: The studied PTCH1 variants may not be associated with BCC development in the Western Mexico population. The PTCH1 mRNA levels were lower in patients with BCC compared to the control group, but its protein was underexpressed in the tissue samples.

Diminished cortical bone density of long bones among children with haemophilic arthropathy.

INTRODUCTION: Children with haemophilia (CwH) have lower bone mineral density in the spine (trabecular bone) than healthy children. There are few studies focusing on bone mineral density in long bones (cortical bone). AIM: To evaluate bi-laterally the distal third of radius and midshaft tibias using quantitative ultrasound (QUS) and assess the speed of sound (SoS). METHODS: A cross-sectional study where 91 CwH and 91 age-matched healthy boys were included. Joint evaluation was determined with the Haemophilia Joint Health Score 2.1 and SoS values. The Z scores were measured with the Sunlight Omnisense 8000 S equipment. RESULTS: Ninety-one CwH (haemophilia A) were evaluated (26 mild form, 26 moderate, and 39 severe). Most patients were treated with on-demand factor replacement and had higher total HJHS scores according to severity (4.8, 14.8 and 14.1, respectively). Patients with moderate and severe disease showed a statistical difference in SoS values for both radius and tibias compared to controls. QUS Z-scores ≥-2 were more frequent in radius and tibias in CwH, but were statistically significant only in tibias when compared to controls (in 30% mild, 46% moderate, 28% severe, respectively). CONCLUSIONS: There was diminished cortical bone density in radius and tibias of CwH compared to healthy controls. Changes predominated in tibias, more frequently affected according to the severity of haemophilia. Early intervention with factor replacement combined with physical activity are key aspects to promote bone health.

Role of Bcl-2, p53, and Ki-67 expression in basal cell carcinoma and their association with aggressive and non-aggressive histological phenotypes.

Introduction: There is increasing evidence that immunohistochemical expression of p53, Ki-67, and Bcl-2 is associated with aggressive (aBCC) and less aggressive (nBCC) histological subtypes and may have a prognostic role. Aim: To investigate the clinicopathological features and immunohistochemical expressions of p53, Ki-67, and Bcl-2 in cutaneous basal cell carcinoma focusing on histological subtypes. Their roles and possible interactions in the development and progression of BCC are discussed. Material and methods: A total of 50 BCC samples from 50 patients from Western Mexico between June 2018 and June 2019 were included. Paraffin-embedded samples were immunostained with p53, Ki-67, and Bcl-2 antibodies. Semi-quantitative analysis was performed to determine the intensity and positivity of immunostained cells. Parametrical and non-parametrical tests were performed according to the sample's distribution. Results: Samples included 21 nBCC and 29 aBCC. The statistical analysis showed statistical association when grouped as non-aggressive and aggressive subtypes for p53 (p = 0.04) and Bcl-2 (p < 0.01). An inverse negative correlation was found between age and Bcl-2 expression. No statistical association was found between Ki-67 immunoreactivity and any of the other variables. Conclusions: We found that a high expression of Bcl-2 and a low expression of p53 was associated with more indolent histopathological features of BCC and therefore better outcomes. These findings suggest that examination of p53 and Bcl-2 expression in BCC patients may provide valuable prognostic information. These biomarkers may play a role in the development and progression of some cases of BCC.

Psoriatic arthritis in patients with psoriasis: A clinical-epidemiological study at a dermatology center in western Mexico.

BACKGROUND/OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory illness. Approximately, 15% of psoriasis patients have undiagnosed PsA. In Mexico, we found no related studies. Our objective was to investigate the clinical-epidemiological characteristics of PsA in psoriasis patients in western Mexico. METHODS: A cross-sectional study including Mexican patients with clinical and histopathological diagnosis of psoriasis. Physical examination, rheumatoid factor analysis and radiographies of axial and peripheral skeleton were performed. The prevalence of PsA using the CASPAR criteria, age, sex; clinical variants of PsA, psoriasis type and the Psoriasis Area and Severity Index (PASI), were assessed. Descriptive and inferential statistics were used. RESULTS: Of 90 patients with psoriasis, 48 met the criteria for PsA, with a prevalence of 53%, and average age of 50 ± 15 years. Predominating were, the female sex in 29 (60%), the axial variant of PsA in 24 (50%), and psoriasis plaques in 40 (83%). The average PASI was 12 ± 11. All cases were rheumatoid factor negative. These variables were not significantly different when comparing subjects with and without PsA, except for the female sex (60% vs. 7%; P < 0.001). CONCLUSIONS: Patients with psoriasis should intentionally be evaluated jointly Dermatologists and Rheumatologists searching joint involvement given the high prevalence of PsA previously undiagnosed.

In vitro evaluation of physicochemical variables on the nematophagous fungus Duddingtonia flagrans.

Duddingtonia flagrans is a biological alternative to the use of anthelmintic drugs in ruminants. This fungus must be ingested by the animal, pass through the cavities of the digestive tract and reach the feces where it develops traps that capture the nematodes. The severe conditions encountered in this process negatively affect the fungus, which is reflected in the low recovery rates compared to the amount administered. The aim of this study was to evaluate independently the in vitro effect of typical physical and chemical conditions of the gastrointestinal cavities of ruminants on the concentration, viability, and the in vitro nematode predatory ability of the chlamydospores of D. flagrans. The factors evaluated individually were pH (2, 6, and 8), temperature (28 ± 2°C and 39 ± 2°C), exposure to artificial saliva, and milling. The results showed that the concentration and viability of D. flagrans were not affected by the action of pH, temperature, milling, or exposure to artificial saliva. Regarding the in vitro nematode predatory ability, a reduction was observed after the milling process and the exposure for 24 h at different pH.

Telehealth-Based Health Coaching Increases m-Health Device Adherence and Rate of Weight Loss in Obese Participants.

Background: Healthy rate of weight loss (RWL) is defined as 1-2 lb of body weight loss per week. Objective: The objective of this study is to investigate changes in adherence to remote monitoring devices and RWL per week in response to a fully online, 12-week, medically monitored, weight management program incorporating weekly video-based health coaching (intervention group [INT]) versus self-guided (control group [CON]). Methods: Twenty-five obese participants (12 males, 13 females) were randomly assigned to either an INT (n = 13, 106.8 ± 25.46 kg, body mass index [BMI] = 35.19 ± 3.91 kg/m2) or CON group (n = 12, 99.8 ± 19.14 kg, BMI = 34.86 ± 4.43 kg/m2). Program related content was derived from inHealth Medical Services, Inc., Telehealth Enabled Approach to Multidisciplinary care (TEAM™) curriculum. All participants were given two wireless devices (Activity Pop and Body Scale; Withings®, Cambridge, MA) that connected them directly with the research team. The INT group connected via telehealth videoconferencing weekly for health coaching with the registered dietitian and monthly for medical monitoring with the physician, while the CON group did not. Both groups connected with the physician and registered dietitian at baseline to establish clinical goals and at the end to review progress. To analyze the data, independent samples t-tests and χ2 tests were performed via SPSS v24 with data displayed as average ± SD; significance set to p < 0.05. Results: The INT group had increased device adherence when compared with CON (92% ± 10% vs. 75% ± 15% scale [p < 0.05]) and (80% ± 14% vs. 49% ± 15% tracker [p < 0.05]). Furthermore, RWL per week was greater in the INT when compared with CON; -0.74 ± 1.8 kg versus 0.18 ± 1.8 kg per week, respectively (p < 0.05). Conclusions: Weekly health coaching via telehealth can be an effective tool to increase remote device adherence and may help to induce a healthy RWL.

Cutaneous melanoma in patients from western Mexico: Clinical pathology characteristics and their relationship to prognosis.

BACKGROUND/OBJECTIVE: Melanoma is the third most frequent malignant neoplasm in skin. The majority of information available comes from studies performed in Caucasian populations. Our objective was to investigate the clinico-pathological characteristics in Mexican patients with cutaneous melanoma and the relationship these characteristics had to prognosis. METHODS: A retrospective study included patients with a histopathological diagnosis of melanoma who were attended at a tertiary level Dermatology Institute over a 10-year period. Age, gender, anatomical location; histopathological subtype, Breslow thickness, Clark level; presence of ulceration, metastasis, anatomical-pathological stage and survival were investigated. To assess the data, descriptive statistics, chi-squared or the Fisher exact test and Kaplan-Meier curves were used. RESULTS: There were 323 patients included. The overall survival rate was 77% with an average follow-up of 7 years. The lowest survival was statistically related to the following: higher age (>65 years), localisation in palms/soles, histopathological nodular subtype, presence of ulceration, Breslow thickness >4.0 mm, Clark level V, the presence of metastasis and stage IV disease. CONCLUSIONS: Our results relay the characteristics and prognosis of patients with the diagnosis of cutaneous melanoma in western Mexico.

Depression and geriatric assessment in older people admitted for hip fracture.

BACKGROUND: Depression is common among older people with hip fracture. AIM: To assess depression scores and other mental and physical health variables in older people with and without depression, admitted to a traumatology ward for a hip fracture. MATERIAL AND METHODS: Cross sectional study of older patients admitted for surgical treatment of hip fracture. Demographic, clinical and laboratory variables were recorded. Twelve surveys were applied to assess general wellbeing, mental health, fall risk, nutritional status, basic and instrumental activities of daily living, social resources and depression (using Yesavage Depression Scale). RESULTS: We assessed 310 patients aged 78 (72-83) years, 72% women. Overall depression prevalence was 46% and its frequency was significantly higher in women, people over 81 years of age, diabetics and subjects with anxiety. The Yesavage score in patients with and without depression was 6.5 and 3, respectively. The median number of medications used by patients with and without depression was 3 and 2 (p < 0.01). CONCLUSIONS: There is a high frequency of depression in these patients, especially in women and subjects older than 81 years of age. Routine geriatric assessments should be performed in hospitalized older patients with hip fracture.

The Retinitis Pigmentosa-Linked Mutations in Transmembrane Helix 5 of Rhodopsin Disrupt Cellular Trafficking Regardless of Oligomerization State.

G protein-coupled receptors can exist as dimers and higher-order oligomers in biological membranes. The specific oligomeric assembly of these receptors is believed to play a major role in their function, and the disruption of native oligomers has been implicated in specific human pathologies. Computational predictions and biochemical analyses suggest that two molecules of rhodopsin (Rho) associate through the interactions involving its fifth transmembrane helix (TM5). Interestingly, there are several pathogenic loss-of-function mutations within TM5 that face the lipid bilayer in a manner that could potentially influence the dimerization of Rho. Though several of these mutations are known to induce misfolding, the pathogenic defects associated with V209M and F220C Rho remain unclear. In this work, we utilized a variety of biochemical and biophysical approaches to elucidate the effects of these mutations on the dimerization, folding, trafficking, and function of Rho in relation to other pathogenic TM5 variants. Chemical cross-linking, bioluminescence energy transfer, and pulsed-interleaved excitation fluorescence cross-correlation spectroscopy experiments revealed that each of these mutants exhibits a wild type-like propensity to self-associate within the plasma membrane. However, V209M and F220C each exhibit subtle defects in cellular trafficking. Together, our results suggest that the RP pathology associated with the expression of the V209M and F220C mutants could arise from defects in folding and cellular trafficking rather than the disruption of dimerization, as has been previously proposed.

Síndrome metabólico y aterosclerosis carotídea subclínica en niños y adolescentes mexicanos con acantosis nigricans.

INTRODUCCIÓN: La acantosis nigricans es un marcador de resistencia a la insulina, la cual se asocia con alteraciones metabólicas y cardiovasculares. OBJETIVO: Investigar la frecuencia de síndrome metabólico y aterosclerosis carotídea subclínica en niños y adolescentes mexicanos con acantosis nigricans y comparar los resultados entre sexos. MÉTODO: Estudio transversal. Se incluyeron 30 sujetos masculinos y 30 femeninos con diagnóstico de acantosis nigricans, menores de 18 años. Se investigó síndrome metabólico (criterios de Cook), riesgo cardiovascular (proteína C reactiva ultrasensible [PCRus]) y aterosclerosis carotídea (grosor íntima-media). Para el análisis de datos se utilizó estadística descriptiva e inferencial. RESULTADOS: La frecuencia de síndrome metabólico fue de 43 % (sexo masculino 42 % versus femenino 58 %, p = 0.58). Todos presentaron niveles anormales de PCRus: 67 % fue clasificado con riesgo cardiovascular moderado y 27 % con riesgo alto. Frecuencia de aterosclerosis carotídea 98 % (masculino 49 % versus femenino 51 %, p = 0.45). La severidad de la acantosis nigricans no influyó en los resultados. CONCLUSIONES: La búsqueda intencionada de síndrome metabólico y aterosclerosis carotídea subclínica en niños y adolescentes mexicanos con acantosis nigricans, independientemente del sexo o severidad de la enfermedad, permitirá implementar medidas para disminuir la morbimortalidad en la edad adulta. INTRODUCTION: Acanthosis nigricans is a marker of insulin resistance that is associated with metabolic and cardiovascular alterations. OBJECTIVE: To investigate the frequency of metabolic syndrome and subclinical carotid atherosclerosis in children and adolescents with acanthosis nigricans, and to compare the results between genders. METHOD: Cross-sectional study, where 30 male and 30 female subjects younger than 18 years of age diagnosed with acanthosis nigricans were included. The presence of metabolic syndrome (Cook's criteria), cardiovascular risk (ultrasensitive C-reactive protein and [us-CRP]), and carotid atherosclerosis (intima-media thickness [IMT]) was investigated. Descriptive and inferential statistics was used for data analysis. RESULTS: The frequency of metabolic syndrome was 43% (males 42 % versus females 58%, p = 0.58). All patients showed us-CRP abnormal levels: 67% were classified with moderate cardiovascular risk and 27% with high risk. The prevalence of carotid atherosclerosis was 98% (males 49% versus females 51%, p = 0.45). Acanthosis nigricans severity did not influence on the results. CONCLUSIONS: Intentional search for metabolic syndrome and subclinical carotid atherosclerosis in Mexican children and adolescents with acanthosis nigricans, regardless of gender or disease severity, will enable the implementation of measures to decrease the morbidity and mortality seen in adult age.

Psoriasis in Children and Adolescents: Epidemiological Study of 280 Patients from Mexico.

BACKGROUND: Psoriasis in children and adolescents has not been well studied in Mexico. OBJECTIVE: To study the epidemiological characteristics of psoriasis in this age group. METHODS: This is a retrospective study in an academic, tertiary care dermatology center from January 1999 to December 2014. We included patients ≤ 18 years of age, with clinical and histopathological diagnosis of psoriasis. We recorded the following information: gender, age, disease duration, clinical variant, nail involvement, treatment, and family history. Descriptive and inferential statistics were used for analysis. RESULTS: Of 2,491 patients with psoriasis, 280 were ≤ 18 years of age, resulting in a prevalence of 11%. There was female predominance and the mean age was 11.5 years. Disease duration was 18 ± 34 months. Plaque psoriasis was the most common form, comprising 191 cases (68%). Nail involvement occurred in only 15 patients (5%). Topical treatment was given to 177 patients (63%). Only 14 cases (5%) had a family history of psoriasis. These variables did not differ when children were compared with adolescents, except in those with a shorter disease duration (13 ± 19 vs. 24 ± 29 months; p = 0.0004). CONCLUSIONS: We found a higher prevalence of psoriasis than previously published studies in this age group and a lower frequency of nail involvement and family history of psoriasis.

A Dynamic Gene Regulatory Network Model That Recovers the Cyclic Behavior of Arabidopsis thaliana Cell Cycle.

Cell cycle control is fundamental in eukaryotic development. Several modeling efforts have been used to integrate the complex network of interacting molecular components involved in cell cycle dynamics. In this paper, we aimed at recovering the regulatory logic upstream of previously known components of cell cycle control, with the aim of understanding the mechanisms underlying the emergence of the cyclic behavior of such components. We focus on Arabidopsis thaliana, but given that many components of cell cycle regulation are conserved among eukaryotes, when experimental data for this system was not available, we considered experimental results from yeast and animal systems. We are proposing a Boolean gene regulatory network (GRN) that converges into only one robust limit cycle attractor that closely resembles the cyclic behavior of the key cell-cycle molecular components and other regulators considered here. We validate the model by comparing our in silico configurations with data from loss- and gain-of-function mutants, where the endocyclic behavior also was recovered. Additionally, we approximate a continuous model and recovered the temporal periodic expression profiles of the cell-cycle molecular components involved, thus suggesting that the single limit cycle attractor recovered with the Boolean model is not an artifact of its discrete and synchronous nature, but rather an emergent consequence of the inherent characteristics of the regulatory logic proposed here. This dynamical model, hence provides a novel theoretical framework to address cell cycle regulation in plants, and it can also be used to propose novel predictions regarding cell cycle regulation in other eukaryotes.

A model of the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva.

BACKGROUND: There are recent experimental reports on the cross-regulation between molecules involved in the control of the cell cycle and the differentiation of the vulval precursor cells (VPCs) of Caenorhabditis elegans. Such discoveries provide novel clues on how the molecular mechanisms involved in the cell cycle and cell differentiation processes are coordinated during vulval development. Dynamic computational models are helpful to understand the integrated regulatory mechanisms affecting these cellular processes. RESULTS: Here we propose a simplified model of the regulatory network that includes sufficient molecules involved in the control of both the cell cycle and cell differentiation in the C. elegans vulva to recover their dynamic behavior. We first infer both the topology and the update rules of the cell cycle module from an expected time series. Next, we use a symbolic algorithmic approach to find which interactions must be included in the regulatory network. Finally, we use a continuous-time version of the update rules for the cell cycle module to validate the cyclic behavior of the network, as well as to rule out the presence of potential artifacts due to the synchronous updating of the discrete model. We analyze the dynamical behavior of the model for the wild type and several mutants, finding that most of the results are consistent with published experimental results. CONCLUSIONS: Our model shows that the regulation of Notch signaling by the cell cycle preserves the potential of the VPCs and the three vulval fates to differentiate and de-differentiate, allowing them to remain completely responsive to the concentration of LIN-3 and lateral signal in the extracellular microenvironment.

Cell patterns emerge from coupled chemical and physical fields with cell proliferation dynamics: the Arabidopsis thaliana root as a study system.

A central issue in developmental biology is to uncover the mechanisms by which stem cells maintain their capacity to regenerate, yet at the same time produce daughter cells that differentiate and attain their ultimate fate as a functional part of a tissue or an organ. In this paper we propose that, during development, cells within growing organs obtain positional information from a macroscopic physical field that is produced in space while cells are proliferating. This dynamical interaction triggers and responds to chemical and genetic processes that are specific to each biological system. We chose the root apical meristem of Arabidopsis thaliana to develop our dynamical model because this system is well studied at the molecular, genetic and cellular levels and has the key traits of multicellular stem-cell niches. We built a dynamical model that couples fundamental molecular mechanisms of the cell cycle to a tension physical field and to auxin dynamics, both of which are known to play a role in root development. We perform extensive numerical calculations that allow for quantitative comparison with experimental measurements that consider the cellular patterns at the root tip. Our model recovers, as an emergent pattern, the transition from proliferative to transition and elongation domains, characteristic of stem-cell niches in multicellular organisms. In addition, we successfully predict altered cellular patterns that are expected under various applied auxin treatments or modified physical growth conditions. Our modeling platform may be extended to explicitly consider gene regulatory networks or to treat other developmental systems.

Learning What Works: A Mixed-Methods Study of American Self-identified Food Conservers.

OBJECTIVE: Identify psychosocial factors influencing food waste mitigation and explore motivations and strategies for successful conservation among self-identified food conservers. METHODS: Mixed-methods study consisting of an online survey estimating food waste production and psychosocial factors and a focus group to explore waste mitigation strategies and motivations. RESULTS: Sampled 27 self-identified conservers (female, aged 18-30 years, White/Asian). Mean household food waste was 6.6 cups/wk (range, 0.0-97.9 cups/wk; median 1.3 cups). Reported waste mitigation strategies include proactive mitigation and adaptive recovery measures in each phase of the food management continuum. Conservers reported various intrinsic and extrinsic motivations to reduce food waste and viewed barriers as manageable. CONCLUSIONS AND IMPLICATIONS: Food conservers act on high intentions to reduce waste by consistently employing both proactive waste mitigation and adaptive food recovery measures. Future research is needed to determine if these findings hold in larger, more diverse samples and link specific behaviors to waste volume.

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients.

BACKGROUND: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. METHODS: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan® probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. RESULTS: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. CONCLUSION: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants.

Nematode predatory ability of the fungus Duddingtonia flagrans affected by in vitro sequential exposure to ovine gastrointestinal tract.

Duddingtonia flagrans is a nematophagous fungus employed as a biocontrol agent of gastrointestinal nematodes in ruminants. After oral ingestion and passage through the digestive tract of animals, this microorganism captures the nematodes in the feces. The drastic conditions of ruminant digestive tract could affect fungi chlamydospores and therefore biocontrol activity. The aim of this study was to evaluate in vitro the effect of four ruminant digestive segments on the concentration and nematode predatory ability of a Colombian native strain of D. flagrans. The sequential four-step methodology proposed evaluated conditions of the oral cavity, rumen, abomasum, and small intestine such as pH (2, 6, 8), enzymes (pepsin, pancreatin), temperature (39 °C), and anaerobiosis comparing short (7 h) and long (51 h) exposure times. The results showed that the nematode predatory ability of the fungi is affected by sequential exposure to gastrointestinal segments and this effect depends on the exposure time to those conditions. After short exposure (7 h) through the four ruminant digestive segments, the fungi had a nematode predatory ability of 62%, in contrast, after long exposure (51 h) the nematode predatory ability was lost (0%). Moreover, the number of broken chlamydospores was higher in the long-exposure assay.

Haplotypes of [-794(CATT)5-8 /-173G>C] MIF gene polymorphisms and its soluble levels in cutaneous squamous cell carcinoma in western Mexican population.

BACKGROUND: Some cytokines are strongly implicated in the development of squamous cell carcinoma (SCC) such as the Macrophage migration inhibitory factor (MIF). The haplotype -794 (CATT)5-8 /-173G>C in MIF gene polymorphisms has been associated with some types of cancer. The aim of this study is to establish the possible association between the presence of this haplotype in the MIF gene and its subsequent soluble levels with the susceptibility of SCC in western Mexican population. METHODS: This study included 175 SCC patients and 175 age-sex-matched individuals as a reference group (RG) from western Mexico. Genomic DNA was extracted from peripheral blood leukocytes. Polymorphisms were genotyped by endpoint PCR and PCR-RFLP, and the determination of MIF serum levels was measured by ELISA. Clinical characteristics were evaluated by a group of dermatologists. RESULTS: Analysis of [-794(CATT)5-8 /-173G>C] MIF gene polymorphisms showed that the 5C (OR = 2.7, p = 0.02) and the 7G (OR = 3.39, p < 0.01) haplotypes are associated with susceptibility in SCC. MIF soluble levels in SCC patients showed a median of 13.93 ng/mL, whereas the reference group showed 6.000 ng/mL. CONCLUSIONS: Our findings suggest that 5C and 7G [-794(CATT)5-8 /-173G>C] MIF gene haplotypes are associated with susceptibility to SCC and that SCC patients present increased soluble levels of MIF.

The Relationship between Fluid Milk, Water, and 100% Juice and Health Outcomes among Children and Adolescents.

Beverages can provide improved nutrient intake and hydration, but also pose concerns related to overnutrition or contamination for children and adolescents who are in a time of critical growth. This narrative review aims to understand the impact of milk, 100% juice, and water consumption on health-related outcomes in youth. The literature review conducted used PubMed, Web of Science, and CABI global. Forty-five research articles met the quality criteria and were included. Health organization and governmental resources were also reviewed to identify current intake and consumption recommendations. All beverages in this review were associated with a variety of desirable and undesirable findings that spanned over 40 different health outcomes. Most studies that assessed milk lacked clear distinction between milk type (flavored vs. unflavored) or fat percentage, making it difficult to understand the impact of milk consumption. The relationship between milk intake and anthropometric-related outcomes were mixed within and across studies. Water was consistently associated with better hydration, while 100% juice and flavored milk intake was associated with more desirable dietary patterns or nutrients that children are currently not consuming adequate amounts of. The implications of these findings were discussed in the context of the National School Lunch Program (NSLP), while considering the impact of issues such as contaminated water and lactose intolerance. This review suggests that water may be an optimal default beverage option in the NSLP to promote hydration and accommodate beverage preferences for those with lactose intolerance.

Transcriptomic and Drug Discovery Analyses Reveal Natural Compounds Targeting the KDM4 Subfamily as Promising Adjuvant Treatments in Cancer.

KDM4 proteins are a subfamily of histone demethylases that target the trimethylation of lysines 9 and 36 of histone H3, which are associated with transcriptional repression and elongation respectively. Their deregulation in cancer may lead to chromatin structure alteration and transcriptional defects that could promote malignancy. Despite that KDM4 proteins are promising drug targets in cancer therapy, only a few drugs have been described as inhibitors of these enzymes, while studies on natural compounds as possible inhibitors are still needed. Natural compounds are a major source of biologically active substances and many are known to target epigenetic processes such as DNA methylation and histone deacetylation, making them a rich source for the discovery of new histone demethylase inhibitors. Here, using transcriptomic analyses we determined that the KDM4 family is deregulated and associated with a poor prognosis in multiple neoplastic tissues. Also, by molecular docking and molecular dynamics approaches, we screened the COCONUT database to search for inhibitors of natural origin compared to FDA-approved drugs and DrugBank databases. We found that molecules from natural products presented the best scores in the FRED docking analysis. Molecules with sugars, aromatic rings, and the presence of OH or O- groups favor the interaction with the active site of KDM4 subfamily proteins. Finally, we integrated a protein-protein interaction network to correlate data from transcriptomic analysis and docking screenings to propose FDA-approved drugs that could be used as multitarget therapies or in combination with the potential natural inhibitors of KDM4 enzymes. This study highlights the relevance of the KDM4 family in cancer and proposes natural compounds that could be used as potential therapies.