RESUMO
Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R. gnavus metabolites can modulate host intestinal physiology remains largely understudied. We performed untargeted metabolomic and bulk RNA-seq analyses using R. gnavus monocolonization in germ-free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R. gnavus in vitro and in nitric oxide synthase 2 (Nos2)-deficient mice. R. gnavus produces specific arginine, tryptophan, and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R. gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R. gnavus induced elevated levels of NOS2, while Nos2 ablation resulted in R. gnavus expansion in vivo. The growth of various R. gnavus strains can be inhibited by NO. Specific R. gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. Intestinal colonization and interaction with R. gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R. gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R. gnavus.
RESUMO
RASopathies are a group of related genetic disorders caused by mutations in genes within the RAS/MAPK signaling pathway. This pathway is crucial for cell division, growth, and differentiation, and its disruption can lead to a variety of developmental and health issues. RASopathies present diverse clinical features and pose significant diagnostic and therapeutic challenges. Studying the landscape of biomarkers in RASopathies has the potential to improve both clinical practices and the understanding of these disorders. This review provides an overview of recent discoveries in RASopathy molecular profiling, which extend beyond traditional gene mutation analysis. mRNAs, non-coding RNAs, protein expression patterns, and post-translational modifications characteristic of RASopathy patients within pivotal signaling pathways such as the RAS/MAPK, PI3K/AKT/mTOR, and Rho/ROCK/LIMK2/cofilin pathways are summarized. Additionally, the field of metabolomics holds potential for uncovering metabolic signatures associated with specific RASopathies, which are crucial for developing precision medicine. Beyond molecular markers, we also examine the role of histological characteristics and non-invasive physiological assessments in identifying potential biomarkers, as they provide evidence of the disease's effects on various systems. Here, we synthesize key findings and illuminate promising avenues for future research in RASopathy biomarker discovery, underscoring rigorous validation and clinical translation.
Assuntos
Biomarcadores , Proteínas ras , Humanos , Biomarcadores/metabolismo , Proteínas ras/metabolismo , Proteínas ras/genética , Transdução de Sinais , Mutação , Mancha Vinho do Porto/genética , Mancha Vinho do Porto/metabolismo , Mancha Vinho do Porto/patologia , Síndrome de Costello/genética , Síndrome de Costello/metabolismo , Síndrome de Costello/patologia , Displasia Ectodérmica/genética , Displasia Ectodérmica/metabolismo , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Insuficiência de Crescimento/genética , Insuficiência de Crescimento/metabolismo , Animais , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , FáciesRESUMO
BACKGROUND: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. METHODS: Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. RESULTS: Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. CONCLUSIONS: The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.
RESUMO
The development of neuroscientific techniques enabling the recording of brain and peripheral nervous system activity has fueled research in cognitive science. Recent technological advancements offer new possibilities for inducing behavioral change, particularly through cost-effective Internet-based interventions. However, limitations in laboratory equipment volume have hindered the generalization of results to real-life contexts. The advent of Internet of Things (IoT) devices, such as wearables, equipped with sensors and microchips, has ushered in a new era in behavior change techniques. Wearables, including smartwatches, electronic tattoos, and more, are poised for massive adoption, with an expected annual growth rate of 55% over the next five years. These devices enable personalized instructions, leading to increased productivity and efficiency, particularly in industrial production. Additionally, the healthcare sector has seen a significant demand for wearables, with over 80% of global consumers willing to use them for health monitoring. This research explores the primary biometric applications of wearables and their impact on users' well-being, focusing on the integration of behavior change techniques facilitated by IoT devices. Wearables have revolutionized health monitoring by providing real-time feedback, personalized interventions, and gamification. They encourage positive behavior changes by delivering immediate feedback, tailored recommendations, and gamified experiences, leading to sustained improvements in health. Furthermore, wearables seamlessly integrate with digital platforms, enhancing their impact through social support and connectivity. However, privacy and data security concerns must be addressed to maintain users' trust. As technology continues to advance, the refinement of IoT devices' design and functionality is crucial for promoting behavior change and improving health outcomes. This study aims to investigate the effects of behavior change techniques facilitated by wearables on individuals' health outcomes and the role of wearables in promoting a healthier lifestyle.
RESUMO
BACKGROUND: Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as Streptococcus mutans and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and Streptococcus mutans. METHODS: We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking. RESULTS: Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in Streptococcus mutans. CONCLUSIONS: Curcumin affects both host carious processes and Streptococcus mutans.
RESUMO
How newly formed memories are preserved while brain plasticity is ongoing has been a source of debate. One idea is that synapses which experienced recent plasticity become resistant to further plasticity, a type of metaplasticity often referred to as saturation. Here, we probe the local dendritic mechanisms that limit plasticity at recently potentiated synapses. We show that recently potentiated individual synapses exhibit a synapse-specific refractory period for further potentiation. We further found that the refractory period is associated with reduced postsynaptic CaMKII signaling; however, stronger synaptic activation only partially restored the ability for further plasticity. Importantly, the refractory period is released after one hour, a timing that coincides with the enrichment of several postsynaptic proteins to pre-plasticity levels. Notably, increasing the level of the postsynaptic scaffolding protein, PSD95, but not of PSD93, overcomes the refractory period. Our results support a model in which potentiation at a single synapse is sufficient to initiate a synapse-specific refractory period that persists until key postsynaptic proteins regain their steady-state synaptic levels.
RESUMO
Synapses form trillions of connections in the brain. Long-term potentiation (LTP) and long-term depression (LTD) are cellular mechanisms vital for learning that modify the strength and structure of synapses. Three-dimensional reconstruction from serial section electron microscopy reveals three distinct pre- to post-synaptic arrangements: strong active zones (AZs) with tightly docked vesicles, weak AZs with loose or non-docked vesicles, and nascent zones (NZs) with a postsynaptic density but no presynaptic vesicles. Importantly, LTP can be temporarily saturated preventing further increases in synaptic strength. At the onset of LTP, vesicles are recruited to NZs, converting them to AZs. During recovery of LTP from saturation (1-4 h), new NZs form, especially on spines where AZs are most enlarged by LTP. Sentinel spines contain smooth endoplasmic reticulum (SER), have the largest synapses and form clusters with smaller spines lacking SER after LTP recovers. We propose a model whereby NZ plasticity provides synapse-specific AZ expansion during LTP and loss of weak AZs that drive synapse shrinkage during LTD. Spine clusters become functionally engaged during LTP or disassembled during LTD. Saturation of LTP or LTD probably acts to protect recently formed memories from ongoing plasticity and may account for the advantage of spaced over massed learning. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
Assuntos
Potenciação de Longa Duração , Depressão Sináptica de Longo Prazo , Plasticidade Neuronal , Sinapses , Animais , Espinhas Dendríticas/fisiologia , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Modelos Neurológicos , Plasticidade Neuronal/fisiologia , Sinapses/fisiologiaRESUMO
Lysozyme is a ß-1,4-glycosidase that hydrolyzes the polysaccharide backbone of bacterial cell walls. With an additional bactericidal function mediated by a separate protein domain, lysozyme is considered a uniquely important antimicrobial molecule contributing to the host's innate immune response to infection. Elevated lysozyme production is found in various inflammatory conditions while patients with genetic risks for inflammatory bowel diseases demonstrate abnormal lysozyme expression, granule packaging, and secretion in Paneth cells. However, it remains unclear how a gain- or loss-of-function in host lysozyme may impact the host inflammatory responses to pathogenic infection. We challenged Lyz1-/- and ectopic Lyz1-expressing (Villin-Lyz1TG) mice with S. Typhimurium and then comprehensively assessed the inflammatory disease progression. We conducted proteomics analysis to identify molecules derived from human lysozyme-mediated processing of live Salmonella. We examined the barrier-impairing effects of these identified molecules in human intestinal epithelial cell monolayer and enteroids. Lyz1-/- mice are protected from infection in terms of morbidity, mortality, and barrier integrity, whereas Villin-Lyz1TG mice demonstrate exacerbated infection and inflammation. The growth and invasion of Salmonella in vitro are not affected by human or chicken lysozyme, whereas lysozyme encountering of live Salmonella stimulates the release of barrier-disrupting factors, InvE-sipC and Lpp1, which directly or indirectly impair the tight junctions. The direct engagement of host intestinal lysozyme with an enteric pathogen such as Salmonella promotes the release of virulence factors that are barrier-impairing and pro-inflammatory. Controlling lysozyme function may help alleviate the inflammatory progression.
Assuntos
Muramidase , Salmonella typhimurium , Muramidase/metabolismo , Animais , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidade , Camundongos , Humanos , Infecções por Salmonella/microbiologia , Infecções por Salmonella/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Camundongos Knockout , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas dos MicrofilamentosRESUMO
BACKGROUND: The location of brain arteriovenous malformations (bAVM) is one of the most relevant prognostic factors included in surgical, endovascular and radiosurgical scores. However, their characteristics according to location are seldom described. The goal of this study was to describe the clinical and angiographic characteristics of bAVM classified according to their location. METHODS: This retrospective observational study included patients diagnosed with bAVM and attending a national referral hospital during the period 2010-2020. Data regarding clinical and angiographic variables were extracted, including characteristics on nidus, arterial afferents, venous drainage and associated aneurysms. BAVM were classified in 8 groups according to their location: frontal, temporal, parieto-occipital, periventricular, deep, cerebellar, brainstem and mixed. Data distribution for each group was determined and between-group differences were assessed. RESULTS: A total of 269 bAVM (in 258 patients) were included. The most frequent location was parieto-occipital; and the least frequent, brainstem. Statistically significant differences were observed between groups for most studied variables, including: clinical presentation, functional status at admission; nidus size and density, classification according to the Spetzler-Martin, Buffalo and modified Pollock-Flickinger scales; number, diameter, origin and type of afferents; number, diameter, type and direction of venous drainage, retrograde venous flow; and presence and size of flow-related aneurysms. CONCLUSION: The clinical and angiographic differences observed between brain AVM groups allow the formulation of profiles according to their location.
Assuntos
Angiografia Cerebral , Malformações Arteriovenosas Intracranianas , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , IdosoRESUMO
BACKGROUND & AIMS: Lacticaseibacillus rhamnosus GG (LGG) is the world's most consumed probiotic but its mechanism of action on intestinal permeability and differentiation along with its interactions with an essential source of signaling metabolites, dietary tryptophan (trp), are unclear. METHODS: Untargeted metabolomic and transcriptomic analyses were performed in LGG monocolonized germ-free mice fed trp-free or -sufficient diets. LGG-derived metabolites were profiled in vitro under anaerobic and aerobic conditions. Multiomic correlations using a newly developed algorithm discovered novel metabolites tightly linked to tight junction and cell differentiation genes whose abundances were regulated by LGG and dietary trp. Barrier-modulation by these metabolites were functionally tested in Caco2 cells, mouse enteroids, and dextran sulfate sodium experimental colitis. The contribution of these metabolites to barrier protection is delineated at specific tight junction proteins and enterocyte-promoting factors with gain and loss of function approaches. RESULTS: LGG, strictly with dietary trp, promotes the enterocyte program and expression of tight junction genes, particularly Ocln. Functional evaluations of fecal and serum metabolites synergistically stimulated by LGG and trp revealed a novel vitamin B3 metabolism pathway, with methylnicotinamide (MNA) unexpectedly being the most robust barrier-protective metabolite in vitro and in vivo. Reduced serum MNA is significantly associated with increased disease activity in patients with inflammatory bowel disease. Exogenous MNA enhances gut barrier in homeostasis and robustly promotes colonic healing in dextran sulfate sodium colitis. MNA is sufficient to promote intestinal epithelial Ocln and RNF43, a master inhibitor of Wnt. Blocking trp or vitamin B3 absorption abolishes barrier recovery in vivo. CONCLUSIONS: Our study uncovers a novel LGG-regulated dietary trp-dependent production of MNA that protects the gut barrier against colitis.
Assuntos
Colite , Lacticaseibacillus rhamnosus , Probióticos , Triptofano , Animais , Lacticaseibacillus rhamnosus/metabolismo , Lacticaseibacillus rhamnosus/fisiologia , Triptofano/metabolismo , Camundongos , Humanos , Células CACO-2 , Probióticos/administração & dosagem , Colite/metabolismo , Colite/patologia , Mucosa Intestinal/metabolismo , Enterócitos/metabolismo , Sulfato de Dextrana , Niacinamida/farmacologia , Niacinamida/metabolismo , Junções Íntimas/metabolismo , Masculino , Modelos Animais de Doenças , Proteínas de Junções Íntimas/metabolismoRESUMO
RASopathies, a group of neurodevelopmental congenital disorders stemming from mutations in the RAS/MAPK pathway, present a unique opportunity to delve into the intricacies of complex neurological disorders. Afflicting approximately one in a thousand newborns, RASopathies manifest as abnormalities across multiple organ systems, with a pronounced impact on the central and peripheral nervous system. In the pursuit of understanding RASopathies' neurobiology and establishing phenotype-genotype relationships, in vivo non-mammalian models have emerged as indispensable tools. Species such as Danio rerio, Drosophila melanogaster, Caenorhabditis elegans, Xenopus species and Gallus gallus embryos have proven to be invaluable in shedding light on the intricate pathways implicated in RASopathies. Despite some inherent weaknesses, these genetic models offer distinct advantages over traditional rodent models, providing a holistic perspective on complex genetics, multi-organ involvement, and the interplay among various pathway components, offering insights into the pathophysiological aspects of mutations-driven symptoms. This review underscores the value of investigating the genetic basis of RASopathies for unraveling the underlying mechanisms contributing to broader neurological complexities. It also emphasizes the pivotal role of non-mammalian models in serving as a crucial preliminary step for the development of innovative therapeutic strategies.
RESUMO
This research paper delves into the effectiveness and impact of behavior change techniques fostered by information technologies, particularly wearables and Internet of Things (IoT) devices, within the realms of engineering and computer science. By conducting a comprehensive review of the relevant literature sourced from the Scopus database, this study aims to elucidate the mechanisms and strategies employed by these technologies to facilitate behavior change and their potential benefits to individuals and society. Through statistical measurements and related works, our work explores the trends over a span of two decades, from 2000 to 2023, to understand the evolving landscape of behavior change techniques in wearable and IoT technologies. A specific focus is placed on a case study examining the application of behavior change techniques (BCTs) for monitoring vital signs using wearables, underscoring the relevance and urgency of further investigation in this critical intersection of technology and human behavior. The findings shed light on the promising role of wearables and IoT devices for promoting positive behavior modifications and improving individuals' overall well-being and highlighting the need for continued research and development in this area to harness the full potential of technology for societal benefit.
Assuntos
Internet das Coisas , Dispositivos Eletrônicos Vestíveis , HumanosRESUMO
Latina Seasonal Farmworkers (LSFW) in South Florida are a community affected by human immunodeficiency virus (HIV) due to cultural barriers, stigma, and lack of awareness of pre-exposure prophylaxis (PrEP). Building on the PROGRESO study, this study sought to: (1) develop and pre-test scientifically supported and culturally tailored PrEP materials for PROGRESO and (2) assess the acceptability of these PrEP materials by LSFW who use alcohol and/or drugs. PrEP messages were selected based on a literature review, feedback from experts working on PrEP programs, and recommendations from a four-member scientific expert panel through a two-level Delphi method. A culturally tailored PrEP presentation was developed and presented to sixteen LSFW, who engaged in four focus groups. Materials were modified based on participants' suggestions. Thematic analysis was used to assess the acceptability and usability of these materials in the LSFW community. Participants responded positively to the PrEP messages and understood their importance for Latinx communities. Participants felt empowered and comfortable enough with the information to distribute the messages to partners, children, and friends with the aid of a physical pamphlet or flyer. A strong cultural context of familialismo and confianza was present in comments made by our participants. This study has the potential to increase LSFW's PrEP awareness and initiation. Future studies may implement a hybrid-interview approach, allowing individuals to self-select into a virtual or in-person focus group. Such flexibility may increase participation and discussion by allowing participants to attend in a format they are most comfortable with, as noted by participants in this study.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Fármacos Anti-HIV/uso terapêutico , Fazendeiros , Hispânico ou Latino , HIV , Infecções por HIV/tratamento farmacológico , Profilaxia Pré-Exposição/métodos , Rede SocialRESUMO
PIK3CA-related overgrowth spectrum (PROS) encompasses different clinical entities caused by somatic activating mutations in PIK3CA. Among PROS, CLOVES syndrome represents a severe phenotype with poor survival rate. We present the case of a 4-month-old girl with CLOVES syndrome successfully treated with alpelisib, a PIKC3A inhibitor.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases , Tiazóis , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Lactente , Tiazóis/uso terapêutico , Malformações Vasculares/genética , Malformações Vasculares/tratamento farmacológico , Nefrocalcinose/genética , Mutação , Lipoma , Anormalidades Musculoesqueléticas , NevoRESUMO
This systematic review and meta-analysis aimed to evaluate the analgesic efficacy and adverse effects of celecoxib after total knee arthroplasty. Keywords in the PubMed and Scopus databases were used to find article abstracts. Each included clinical trial was assessed using the Cochrane Collaboration risk of bias tool, and we extracted data on postoperative pain assessment using the Visual Analogue Scale (VAS) at rest, ambulation, and active range of motion, rescue analgesic intake, and adverse effects. Inverse variance tests with mean differences were used to analyze the numerical variables. The Mantel-Haenszel statistical method and the odds ratio were used to evaluate the dichotomous data. According to this qualitative assessment (n = 482), two studies presented conclusions in favor of celecoxib (n = 187), one showed similar results between celecoxib and the placebo (n = 44), and three clinical trials did not draw conclusions as to the effectiveness of celecoxib versus the placebo (n = 251). Moreover, the evaluation of the rescue analgesic intake showed that the patients receiving celecoxib had a lower intake compared to patients receiving a placebo (n = 278, I2 = 82%, p = 0.006, mean difference = -6.89, 95% IC = -11.76 to -2.02). In conclusion, the pooled analysis shows that administration of celecoxib alone results in a decrease in rescue analgesic consumption compared to a placebo after total knee surgery.
RESUMO
Current advances in the management of the autonomic nervous system in various cardiovascular diseases, and in treatments for pain or sympathetic disturbances in the head, neck, or upper limbs, necessitate a thorough understanding of the anatomy of the cervicothoracic sympathetic trunk. Our objective was to enhance our understanding of the origin and distribution of communicating branches and visceral cervicothoracic sympathetic nerves in human fetuses. This was achieved through a comprehensive topographic systematization of the branching patterns observed in the cervical and upper thoracic ganglia, along with the distribution of communicating branches to each cervical spinal nerve. We conducted detailed sub-macroscopic dissections of the cervical and thoracic regions in 20 human fetuses (40 sides). The superior and cervicothoracic ganglia were identified as the cervical sympathetic ganglia that provided the most communicating branches on both sides. The middle and accessory cervical ganglia contributed the fewest branches, with no significant differences between the right and left sides. The cervicothoracic ganglion supplied sympathetic branches to the greatest number of spinal nerves, spanning from C5 to T2 . The distribution of communicating branches to spinal nerves was non-uniform. Notably, C3 , C4 , and C5 received the fewest branches, and more than half of the specimens showed no sympathetic connections. C1 and C2 received sympathetic connections exclusively from the superior ganglion. Spinal nerves that received more branches often did so from multiple ganglia. The vertebral nerve provided deep communicating branches primarily to C6 , with lesser contributions to C7 , C5 , and C8 . The vagus nerve stood out as the cranial nerve with the most direct sympathetic connections. The autonomic branching pattern and connections of the cervicothoracic sympathetic trunk are significantly variable in the fetus. A comprehensive understanding of the anatomy of the cervical and upper thoracic sympathetic trunk and its branches is valuable during autonomic interventions and neuromodulation. This knowledge is particularly relevant for addressing various autonomic cardiac diseases and for treating pain and vascular dysfunction in the head, neck, and upper limbs.
RESUMO
The role played by type 2 diabetes mellitus (DM2) in the occurrence of recurrent tuberculosis is still uncertain. Military personnel are an occupational group with an increased risk for tuberculosis exposure due to their activities. Methods. We conducted a retrospective cohort to study the association between DM2 and recurrent TB in military workers who have been previously treated for tuberculosis at the Central Military Hospital in Lima, Peru, between 2016 and 2017. We evaluated the risk between DM2 and recurrent TB using Nelson-Aalen graphical analysis and Cox regression stratified by TB cured with hazard ratio (HR) calculation adjusted for confounders. Results. We evaluated 220 workers with a mean age of 23.2 ± 7.8 years (96.8 % male). DM2 and recurrent TB frequency were 11.8 % and 5.0 %, respectively. Those with DM (36.5 %) presented a greater proportion of recurrent TB than those without DM2 (10.5 %). The cumulative risk for recurrent TB increases faster among workers with DM2 (p = 0.025, LR chi-squared test). Cox regression stratified by type of cured TB did not show an association between DM2 and recurrent TB (HR: 3.67; 95 %CI: 1.00-13.46). Conclusion. The cumulative risk for recurrent TB increases faster in patients with DM than in those without DM2. DM2 is not associated with the time of apparition of recurrent TB in military workers.
RESUMO
Intestinal microbiota confers susceptibility to diet-induced obesity, yet many probiotic species that synthesize tryptophan (trp) actually attenuate this effect, although the underlying mechanisms are unclear. We monocolonized germ-free mice with a widely consumed probiotic Lacticaseibacillus rhamnosus GG (LGG) under trp-free or -sufficient dietary conditions. We obtained untargeted metabolomics from the mouse feces and serum using liquid chromatography-mass spectrometry and obtained intestinal transcriptomic profiles via bulk-RNA sequencing. When comparing LGG-monocolonized mice with germ-free mice, we found a synergy between LGG and dietary trp in markedly promoting the transcriptome of fatty acid metabolism and ß-oxidation. Upregulation was specific and was not observed in transcriptomes of trp-fed conventional mice and mice monocolonized with Ruminococcus gnavus. Metabolomics showed that fecal and serum metabolites were also modified by LGG-host-trp interaction. We developed an R-Script-based MEtabolome-TRanscriptome Correlation Analysis algorithm and uncovered LGG- and trp-dependent metabolites that were positively or negatively correlated with fatty acid metabolism and ß-oxidation gene networks. This high-throughput metabolome-transcriptome correlation strategy can be used in similar investigations to reveal potential interactions between specific metabolites and functional or disease-related transcriptomic networks.
Assuntos
Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Camundongos , Animais , Intestinos , Microbioma Gastrointestinal/genética , Perfilação da Expressão Gênica , Ácidos GraxosAssuntos
Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Leiomioma/cirurgia , Neoplasias Uterinas/cirurgiaRESUMO
Fructose consumption has increased globally and has been linked to obesity, insulin resistance, and diabetes. Selenium nanoparticles (SeNPs) can regulate glucose and lipid concentrations and have immunoregulatory properties. Four study groups (n = 7/group) of eight-week-old male mice (Balb/c) were formed for this investigation. One group received a standard diet (C), another standard diet plus SeNPs (C + SeNPs), a high fructose diet (F), and a group with a high fructose diet plus SeNPs (F + SeNPs). Weight, glucose, triglycerides, and cholesterol were evaluated. In the end, mice were sacrificed, blood samples were obtained to assess cytokine profile, and liver, kidney, and pancreas were removed for histological examination. The study was complemented with an in silico analysis where the CTD, STITCH, ToppGene Suite, ShinyGO 0.76.3 databases, and Cytoscape software were implemented. The results of in vivo analysis showed that SeNPs regulated biochemical parameters and showed anti-inflammatory effects by decreasing the concentrations of TNF-alpha, IL-1beta, and IFN-gamma and increasing IL-10. No damage was observed in the studied organs. In addition, SeNPs regulate oxidative stress, preserve cell organelles, and regulate metabolic pathways to avoid the adverse effects of fructose consumption, according to bioinformatics analysis. In conclusion, SeNPs protect against the undesirable effects of a diet rich in fructose.