RESUMO
Talaromycosis is an invasive mycosis endemic in tropical and subtropical Asia and is caused by the pathogenic fungus Talaromyces marneffei. Approximately 17,300 cases of T. marneffei infection are diagnosed annually, and the reported mortality rate is extremely high (~1/3). Despite the devastating impact of talaromycosis on immunocompromised individuals, particularly HIV-positive persons, and the increase in reported occurrences in HIV-uninfected persons, diagnostic and therapeutic approaches for talaromycosis have received far too little attention worldwide. In 2021, scientists living in countries where talaromycosis is endemic raised a global demand for it to be recognized as a neglected tropical disease. Therefore, T. marneffei and the infectious disease induced by this fungus must be treated with concern. T. marneffei is a thermally dimorphic saprophytic fungus with a complicated mycological growth process that may produce various cell types in its life cycle, including conidia, hyphae, and yeast, all of which are associated with its pathogenicity. However, understanding of the pathogenic mechanism of T. marneffei has been limited until recently. To achieve a holistic view of T. marneffei and talaromycosis, the current knowledge about talaromycosis and research breakthroughs regarding T. marneffei growth biology are discussed in this review, along with the interaction of the fungus with environmental stimuli and the host immune response to fungal infection. Importantly, the future research directions required for understanding this serious infection and its causative pathogenic fungus are also emphasized to identify solutions that will alleviate the suffering of susceptible individuals worldwide.
Assuntos
Micoses , Talaromyces , Humanos , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/epidemiologia , VirulênciaRESUMO
NKAP mutations are associated with Hackmann-Di Donato-type X-linked syndromic intellectual developmental disorder (MRXSHD, MIM: #301039). Here, we elucidate the potential prenatal manifestation of NKAP mutation-associated disorder for the first time, alongside revealing the relationship between NKAP mutations and congenital heart defect (CHD) in the Chinese population. An NKAP mutation (NM_024528.4: c.988C>T, p.Arg330Cys) was identified in two foetuses presenting with CHD. Subsequent mechanistic exploration revealed a marked downregulation of NKAP transcription within HEK293T cells transfected with NKAP p.R330C. However, no significant change was observed at the protein level. Moreover, the mutation led to a dysregulation in the transcription of genes associated with cardiac morphogenesis, such as DHRS3, DNAH11 and JAG1. Additionally, our research determined that NKAP p.R330C affected Nkap protein intra-nuclear distribution, and binding with Hdac3. Summarily, our study strengthens NKAP mutations as a cause of CHD and prompts the reclassification of NKAP p.R330C as likely pathogenic, thereby establishing a prospective prenatal phenotypic spectrum that provides new insight into the prenatal diagnosis of CHD. Our findings also provide evidence of NKAP p.R330C pathogenicity and demonstrate the potential mechanism by which p.R330C dysregulates cardiac developmental gene transcription by altering Nkap intra-nuclear distribution and obstructing the interaction between Nkap and Hdac3, thereby leading to CHD.
Assuntos
Cardiopatias Congênitas , Mutação , Fenótipo , Humanos , Cardiopatias Congênitas/genética , Mutação/genética , Feminino , Células HEK293 , Predisposição Genética para Doença , Masculino , GravidezRESUMO
Immune checkpoints are essential regulators of immune responses, either by activating or suppressing them. Consequently, they are regarded as pivotal elements in the management of infections, cancer, and autoimmune disorders. In recent years, researchers have identified numerous soluble immune checkpoints that are produced through various mechanisms and demonstrated biological activity. These soluble immune checkpoints can be produced and distributed in the bloodstream and various tissues, with their roles in immune response dysregulation and autoimmunity extensively documented. This review aims to provide a thorough overview of the generation of various soluble immune checkpoints, such as sPD-1, sCTLA-4, sTim-3, s4-1BB, sBTLA, sLAG-3, sCD200, and the B7 family, and their importance as indicators for the diagnosis and prediction of autoimmune conditions. Furthermore, the review will investigate the potential pathological mechanisms of soluble immune checkpoints in autoimmune diseases, emphasizing their association with autoimmune diseases development, prognosis, and treatment.
Assuntos
Doenças Autoimunes , Proteínas de Checkpoint Imunológico , Humanos , Doenças Autoimunes/imunologia , Doenças Autoimunes/diagnóstico , Proteínas de Checkpoint Imunológico/metabolismo , Proteínas de Checkpoint Imunológico/genética , Biomarcadores , Animais , Autoimunidade , Prognóstico , Suscetibilidade a Doenças/imunologiaRESUMO
Reticulitermes chinensis Snyder is an important pest in forestry and construction and is widely distributed in China. We found that Serratia marcescens Bizio strain SM1 has insecticidal activity to R. chinensis, but the pathogenic mechanism of SM1 to R. chinensis is not clear. Therefore, full-length transcriptome sequencing was performed on R. chinensis infected with SM1 and the control group. A total of 230 differentially expressed genes were identified by comparing SM1 infection group and the control group, among which 103 were downregulated and 127 were upregulated. We found downregulated genes in nine metabolic pathway categories, among which carbohydrate metabolism had the most downregulated genes, followed by energy metabolism and amino acid metabolism. We also found that some downregulated genes were related to pattern recognition receptors, cellular immunity, and humoral immunity, indicating that R. chinensis immunity was negatively affected by SM1 infection. In addition, some genes in signal transduction and genetic information processing pathways were downregulated. In this study, high-throughput full-length transcriptome analysis was used to analyse the pathogenic mechanism of SM1 to R. chinensis. The results of this study provide useful information for exploring the relationship between SM1 and R. chinensis, and provide theoretical support for the future application of SM1 and the prevention and treatment of R. chinensis.
Assuntos
Serratia marcescens , Transcriptoma , Serratia marcescens/genética , Animais , Mariposas/microbiologia , Mariposas/genética , Mariposas/imunologia , Perfilação da Expressão GênicaRESUMO
Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Sepse , Humanos , Medicina Tradicional Chinesa , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Apoptose , Transdução de Sinais , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
Mutations in the polyglutamine tract-binding protein 1 (PQBP1) gene are associated with Renpenning syndrome, which is characterized by microcephaly, intellectual deficiency, short stature, small testes, and distinct facial dysmorphism. Studies using different models have revealed that PQBP1 plays essential roles in neural development and function. In this mini-review, we summarize recent findings relating to the roles of PQBP1 in these processes, including in the regulation of neural progenitor proliferation, neural projection, synaptic growth, neuronal survival, and cognitive function via mRNA transcription and splicing-dependent or -independent processes. The novel findings provide insights into the mechanisms underlying the pathogenesis of Renpenning syndrome and may advance drug discovery and treatment for this condition.
Assuntos
Paralisia Cerebral , Deficiência Intelectual , Deficiência Intelectual Ligada ao Cromossomo X , Humanos , Proteínas de Transporte/química , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/patologia , Mutação , Paralisia Cerebral/genética , Paralisia Cerebral/patologia , Deficiência Intelectual/genética , Proteínas de Ligação a DNA/genéticaRESUMO
BACKGROUND: Electronic cigarette (e-cig) use is increasing worldwide, especially among young individuals. Spirometry measures airflow obstruction and is the primary tool for diagnosing/monitoring respiratory diseases in clinical settings. This study aims to assess the effects of chronic e-cig exposure on spirometric traits, and directly compare to conventional combustible-cigarette (c-cig). METHODS: We employed an e- and c-cig aerosol generation system that resembled human smoking/vaping scenario. Fifty 6-week old C57BL/6 mice were equally divided into five groups and exposed to clean air (control), e-cig aerosol (low- and high-dose), and c-cig aerosol (low- and high-dose), respectively, for 10 weeks. Afterwards, growth trajectory, spirometry and pulmonary pathology were analyzed. RESULTS: Both e- and c-cig exposure slowed down growth and weight gain. Low dose e-cig exposure (1 h exposure per day) resulted in minimal respiratory function damage. At high dose (2 h exposure per day), e-cig exposure deteriorated 7 spirometry traits but by a smaller magnitude than c-cig exposure. For example, comparing to clean air controls, high dose e- and c-cig exposure increased inspiratory resistance by 24.3% (p = 0.026) and 66.7% (p = 2.6e-5), respectively. Low-dose e-cig exposure increased alveolar macrophage count but did not lead to airway remodeling. In contrast, even low-dose c-cig caused alveoli break down and thickening of the small airway, hallmarks of airway obstructive disease. CONCLUSIONS: We conducted well-controlled animal exposure experiments assessing chronic e-cig exposure's effects on spirometry traits. Further, mechanistic study characterized airway remodeling, alveolar tissue lesion and inflammation induced by e- and c-cig exposure. Our findings provided scientific and public health insights on e-cig's health consequences, especially in adolescent users.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar , Produtos do Tabaco , Humanos , Camundongos , Animais , Adolescente , Remodelação das Vias Aéreas , Camundongos Endogâmicos C57BL , Aerossóis e Gotículas Respiratórios , Lesão Pulmonar/induzido quimicamenteRESUMO
Psoriasis is a chronic skin disease that affects millions of people worldwide. In 2014, psoriasis was recognized by the World Health Organization (WHO) as a serious non-communicable disease. In this study, a systems biology approach was used to investigate the underlying pathogenic mechanism of psoriasis and identify the potential drug targets for therapeutic treatment. The study involved the construction of a candidate genome-wide genetic and epigenetic network (GWGEN) through big data mining, followed by the identification of real GWGENs of psoriatic and non-psoriatic using system identification and system order detection methods. Core GWGENs were extracted from real GWGENs using the Principal Network Projection (PNP) method, and the corresponding core signaling pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Comparing core signaling pathways of psoriasis and non-psoriasis and their downstream cellular dysfunctions, STAT3, CEBPB, NF-κB, and FOXO1 are identified as significant biomarkers of pathogenic mechanism and considered as drug targets for the therapeutic treatment of psoriasis. Then, a deep neural network (DNN)-based drug-target interaction (DTI) model was trained by the DTI dataset to predict candidate molecular drugs. By considering adequate regulatory ability, toxicity, and sensitivity as drug design specifications, Naringin, Butein, and Betulinic acid were selected from the candidate molecular drugs and combined into potential multi-molecule drugs for the treatment of psoriasis.
Assuntos
Psoríase , Biologia de Sistemas , Humanos , Reposicionamento de Medicamentos , Psoríase/tratamento farmacológico , Psoríase/genética , Análise em Microsséries , Redes Neurais de ComputaçãoRESUMO
Alzheimer's disease (AD) is a prevalent degenerative condition that is increasingly affecting populations globally. American ginseng (AG) has anti-AD bioactivity, and ginsenosides, as the main active components of AG, have shown strong anti-AD effects in both in vitro and in vivo studies. It has been reported that ginsenosides can inhibit amyloid ß-protein (Aß) production and deposition, tau phosphorylation, apoptosis and cytotoxicity, as well as possess anti-oxidant and anti-inflammatory properties, thus suppressing the progression of AD. In this review, we aim to provide a comprehensive overview of the pathogenesis of AD, the potential anti-AD effects of ginsenosides found in AG, and the underlying molecular mechanisms associated with these effects. Additionally, we will discuss the potential use of AG in the treatment of AD, and how ginsenosides in AG may exert more potent anti-AD effects in vivo may be a direction for further research.
Assuntos
Doença de Alzheimer , Ginsenosídeos , Panax , Humanos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , ApoptoseRESUMO
Diverse manifestations have been recognized to last for a long time in patients infected with SARS-CoV-2. However, understanding of oral sequelae after recovery from COVID-19 is relatively poor compared to that of oral symptoms in the acute phase of COVID-19 and other COVID-19 sequelae. The aim of the present study was to characterize persistent gustatory and saliva secretory dysfunctions and to speculate on their pathogenic mechanisms. Articles were retrieved by searching scientific databases with a cutoff date of September 30, 2022. The literature search indicated that ageusia/dysgeusia and xerostomia/dry mouth are reported by 1-45% of COVID-19 survivors at follow-ups of 21-365 days and by 2-40% of COVID-19 survivors at follow-ups of 28-230 days, respectively. The prevalence of gustatory sequelae partly depends on difference in ethnicity, gender, age, and disease severity of subjects. Co-occurring gustatory and saliva secretory sequelae are pathogenically related to either or both of the following: expression of SARS-CoV-2 cellular entry-relevant receptors in taste buds and salivary glands, and SARS-CoV-2 infection-induced deficiency in zinc that is essential for normality of taste perception and saliva secretion. Given the long-term oral sequelae, hospital discharge is not the end of the disease; therefore, careful attention should be continuously paid to oral conditions of post-COVID-19 patients.
Assuntos
COVID-19 , Transtornos do Olfato , Humanos , COVID-19/complicações , SARS-CoV-2 , Saliva , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologia , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Progressão da DoençaRESUMO
Acute pancreatitis (AP) is a common clinical abdominal emergency, with a high and increasing incidence each year. Severe AP can easily cause systemic inflammatory response syndrome, multiple organ dysfunction and other complications, leading to higher hospitalization rates and mortality. Currently, there is no specific treatment for AP. Thus, we still need to understand the exact AP pathogenesis to effectively cure AP. With the rise of transcriptomics, RNA molecules, such as microRNAs (miRNAs) transcribed from nonprotein-coding regions of biological genomes, have been found to be of great significance in the regulation of gene expression and to be involved in the occurrence and development of many diseases. Increasing evidence has shown that miRNAs, as regulatory RNAs, can regulate pancreatic acinar necrosis and apoptosis and local and systemic inflammation and play an important role in the development and thus potentially the diagnosis and treatment of AP. Therefore, here, the current research on the relationship between miRNAs and AP is reviewed.
Assuntos
MicroRNAs , Pancreatite , Doença Aguda , Apoptose , Humanos , Inflamação , MicroRNAs/genética , Pancreatite/genética , Pancreatite/terapiaRESUMO
Hyperglycemia in diabetic patients is associated with abnormally-elevated cellular glucose levels. It is hypothesized that increased cellular glucose will lead to increased formation of endogenous methanol and/or formaldehyde, both of which are then metabolically converted to formic acid. These one-carbon metabolites are known to be present naturally in humans, and their levels are increased under diabetic conditions. Mechanistically, while formaldehyde is a cross-linking agent capable of causing extensive cytotoxicity, formic acid is an inhibitor of mitochondrial cytochrome oxidase, capable of inducing histotoxic hypoxia, ATP deficiency and cytotoxicity. Chronic increase in the production and accumulation of these toxic one-carbon metabolites in diabetic patients can drive the pathogenesis of ocular as well as other diabetic complications. This hypothesis is supported by a large body of experimental and clinical observations scattered in the literature. For instance, methanol is known to have organ- and species-selective toxicities, including the characteristic ocular lesions commonly seen in humans and non-human primates, but not in rodents. Similarly, some of the diabetic complications (such as ocular lesions) also have a characteristic species-selective pattern, closely resembling methanol intoxication. Moreover, while alcohol consumption or combined use of folic acid plus vitamin B is beneficial for mitigating acute methanol toxicity in humans, their use also improves the outcomes of diabetic complications. In addition, there is also a large body of evidence from biochemical and cellular studies. Together, there is considerable experimental support for the proposed hypothesis that increased metabolic formation of toxic one-carbon metabolites in diabetic patients contributes importantly to the development of various clinical complications.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Animais , Carbono , Retinopatia Diabética/etiologia , Formaldeído , Formiatos , Glucose , Humanos , Metanol/metabolismoRESUMO
The pinewood nematode, Bursaphelenchus xylophilus, has been determined as one of the world's top ten plant-parasitic nematodes. It causes pine wilt, a progressive disease that affects the economy and ecologically sustainable development in East Asia. B. xylophilus secretes pathogenic proteins into host plant tissues to promote infection. However, little is known about the interaction between B. xylophilus and pines. Previous studies reported transthyretin proteins in some species and their strong correlation with immune evasion, which has also been poorly studied in B. xylophilus. In this study, we cloned and functionally validated the B. xylophilus pathogenic protein BxTTR-52, containing a transthyretin domain. An in situ hybridization assay demonstrated that BxTTR-52 was expressed mainly in the esophageal glands of B. xylophilus. Confocal microscopy revealed that BxTTR-52-RFP localized to the nucleus, cytoplasm, and plasma membrane. BxTTR-52 recombinant proteins produced by Escherichia coli could be suppressed by hydrogen peroxide and antioxidant enzymes in pines. Moreover, silencing BxTTR-52 significantly attenuated the morbidity of Pinus thunbergii infected with B. xylophilus. It also suppressed the expression of pathogenesis-related genes in P. thunbergii. These results suggest that BxTTR-52 suppresses the plant immune response in the host pines and might contribute to the pathogenicity of B. xylophilus in the early infection stages.
Assuntos
Pinus , Rabditídios , Tylenchida , Animais , Tylenchida/genética , Pinus/parasitologia , Virulência , Imunidade Inata , Doenças das Plantas/parasitologiaRESUMO
Connexin(Cx) plays an important role in ensuring the material exchange and information transmission between cells and maintaining the stability of the skin barrier.The gene mutations and even the abnormal expression levels of Cx can cause a variety of diseases,which will seriously affect the quality of life of patients.The human body carries 21 genes encoding connexins,the mutations of which are associated with at least 14 clinical concomitant diseases.The existence of Cx43 with wide distribution has been reported in most organs and tissues.Moreover,Cx43 is a key regulatory node in important physiological and pathological processes such as wound healing,skin keratinization,and skin tumor development.This review focuses on the recent research achievements of the role of Cx43(GJA1) gene in the skin barrier,the skin diseases associated with GJA1 gene mutations,and the potential pathogenic mechanisms.It is expected to provide reference for the prevention and treatment of Cx43 clinical complications and the related research.
Assuntos
Conexina 43 , Dermatopatias , Humanos , Conexina 43/genética , Conexina 43/metabolismo , Qualidade de Vida , Conexinas/genética , Mutação , Dermatopatias/genéticaRESUMO
Botryosphaeria dothidea is a pathogen with worldwide distribution, infecting hundreds of species of economically important woody plants. It infects and causes various symptoms on apple plants, including wart and canker on branches, twigs, and stems. However, the mechanism of warts formation is unclear. In this study, we investigated the mechanism of wart formation by observing the transection ultrastructure of the inoculated cortical tissues at various time points of the infection process and detecting the expression of genes related to the pathogen pathogenicity and plant defense response. Results revealed that wart induced by B. dothidea consisted of proliferous of phelloderm cells, the newly formed secondary phellem, and the suberized phelloderm cells surrounding the invading mycelia. The qRT-PCR analysis revealed the significant upregulation of apple pathogenesis-related and suberification-related genes and a pathogen cutinase gene Bdo_10846. The Bdo_10846 knockout transformants showed reduced cutinase activity and decreased virulence. Transient expression of Bdo_10846 in Nicotiana benthamiana induced ROS burst, callose formation, the resistance of N. benthamiana to Botrytis cinerea, and significant upregulation of the plant pathogenesis-related and suberification-related genes. Additionally, the enzyme activity is essential for the induction. Virus-induced gene silencing demonstrated that the NbBAK1 and NbSOBIR1 expression were required for the Bdo_10846 induced defense response in N. benthamiana. These results revealed the mechanism of wart formation induced by B. dothidea invasion and the important roles of the cutinase Bdo_10846 in pathogen virulence and in inducing plant immunity.
Assuntos
Ascomicetos/genética , Hidrolases de Éster Carboxílico/genética , Proteínas Fúngicas/genética , Malus/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Ascomicetos/patogenicidade , Hidrolases de Éster Carboxílico/classificação , Hidrolases de Éster Carboxílico/metabolismo , Proteínas Fúngicas/classificação , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno/genética , Malus/microbiologia , Filogenia , Doenças das Plantas/microbiologia , Imunidade Vegetal/genética , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Virulência/genéticaRESUMO
Puccinia striiformis f. sp. tritici (Pst) is an important pathogen of wheat (Triticum aestivum L.) stripe rust, and the effector protein secreted by haustoria is a very important component involved in the pathogenic process. Although the candidate effector proteins secreted by Pst haustoria have been predicted to be abundant, few have been functionally validated. Our study confirmed that chitin and flg22 could be used as elicitors of the pathogenic-associated molecular pattern-triggered immune (PTI) reaction in wheat leaves and that TaPr-1-14 could be used as a marker gene to detect the PTI reaction. In addition, the experimental results were consistent in wheat protoplasts. A rapid and efficient method for screening and identifying the effector proteins of Pst was established by using the wheat protoplast transient expression system. Thirty-nine Pst haustorial effector genes were successfully cloned and screened for expression in the protoplast. We identified three haustorial effector proteins, PSEC2, PSEC17, and PSEC45, that may inhibit the response of wheat to PTI. These proteins are localized in the somatic cytoplasm and nucleus of wheat protoplasts and are highly expressed during the infection and parasitism of wheat.
Assuntos
Proteínas Fúngicas/metabolismo , Imunidade , Moléculas com Motivos Associados a Patógenos/metabolismo , Protoplastos/microbiologia , Puccinia/fisiologia , Triticum/imunologia , Triticum/microbiologia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Quitina/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Imunidade/efeitos dos fármacos , Doenças das Plantas/microbiologia , Imunidade Vegetal/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/imunologia , Folhas de Planta/microbiologia , Protoplastos/efeitos dos fármacos , Puccinia/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reprodutibilidade dos Testes , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Transcrição Gênica/efeitos dos fármacos , Triticum/efeitos dos fármacos , Triticum/genéticaRESUMO
AIMS/HYPOTHESIS: Retinal microvascular diameters are biomarkers of cardio-metabolic risk. However, the association of (pre)diabetes with retinal microvascular diameters remains unclear. We aimed to investigate the association of prediabetes (impaired fasting glucose or impaired glucose tolerance) and type 2 diabetes with retinal microvascular diameters in a predominantly white population. METHODS: In a population-based cohort study with oversampling of type 2 diabetes (N = 2876; n = 1630 normal glucose metabolism [NGM], n = 433 prediabetes and n = 813 type 2 diabetes, 51.2% men, aged 59.8 ± 8.2 years; 98.6% white), we determined retinal microvascular diameters (measurement unit as measured by retinal health information and notification system [RHINO] software) and glucose metabolism status (using OGTT). Associations were assessed with multivariable regression analyses adjusted for age, sex, waist circumference, smoking, systolic blood pressure, lipid profile and the use of lipid-modifying and/or antihypertensive medication. RESULTS: Multivariable regression analyses showed a significant association for type 2 diabetes but not for prediabetes with arteriolar width (vs NGM; prediabetes: ß = 0.62 [95%CI -1.58, 2.83]; type 2 diabetes: 2.89 [0.69, 5.08]; measurement unit); however, there was a linear trend for the arteriolar width across glucose metabolism status (p for trend = 0.013). The association with wider venules was not statistically significant (prediabetes: 2.40 [-1.03, 5.84]; type 2 diabetes: 2.87 [-0.55, 6.29], p for trend = 0.083; measurement unit). Higher HbA1c levels were associated with wider retinal arterioles (standardised ß = 0.043 [95% CI 0.00002, 0.085]; p = 0.050) but the association with wider venules did not reach statistical significance (0.037 [-0.006, 0.080]; p = 0.092) after adjustment for potential confounders. CONCLUSIONS/INTERPRETATION: Type 2 diabetes, higher levels of HbA1c and, possibly, prediabetes, are independently associated with wider retinal arterioles in a predominantly white population. These findings indicate that microvascular dysfunction is an early phenomenon in impaired glucose metabolism.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Vasos Retinianos/patologia , Arteríolas/metabolismo , Arteríolas/fisiopatologia , Pressão Sanguínea/fisiologia , Estudos de Coortes , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Análise de RegressãoRESUMO
Pasteurella multocida possesses a viscous capsule polysaccharide on the cell surface, which is a critical structural component and virulence factor. Capsular polysaccharides are structurally similar to vertebrate glycosaminoglycans, providing an immunological mechanism for bacterial molecular mimicry, resistance to phagocytosis, and immune evasion during the infection process. Based on the capsular antigen, P. multocida is divided into A, B, D, E, and F five serogroups. Previously, we systematically reported the biosynthesis and regulation mechanisms of the P. multocida capsule. In this paper, we take serogroup A capsular polysaccharide as the representative, systematically illuminating the P. multocida capsular virulence and epidemiology, molecular camouflage, adhesion and colonization, anti-phagocytosis, anti-complement system, cell invasion and signal transduction mechanism, to provide a theoretical basis for the research of molecular pathogenic mechanism of P. multocida capsule and the development of polysaccharides vaccine.
Assuntos
Infecções por Pasteurella , Pasteurella multocida , Cápsulas Bacterianas , Humanos , Ácido Hialurônico , Virulência , Fatores de VirulênciaRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and Authors. Professor Michael Müller approached the journal explaining that he had encountered an issue in the way the spectrofluorometric data analyses was performed. The normalization of the fluorescence curves to their respective starting points (as explained in Figure 1A) overestimated the changes in Mecp2-mutant mice, which usually started at lower levels. This overestimation applies to Figure 3 A-D as well as Table 2 and Table 3 and altered the outcomes of the study. Both the EiC and the authors agreed that a corrigendum would not be appropriate due to the change in conclusion and that the paper should therefore be retracted. The authors apologise for any confusion this paper may have resulted in.
Assuntos
Encéfalo/metabolismo , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/metabolismo , Síndrome de Rett/metabolismo , Animais , Feminino , Longevidade/fisiologia , Masculino , Camundongos , Estresse Oxidativo/fisiologiaRESUMO
Oral tumors are malignant cancers caused by abnormal proliferation or pathological changes of soft or hard tissues in the oral cavity. Serious cases may pose a threat to life. However, its precancerous lesions remain unclear. This study is based on a comprehensive strategy to explore a multi-factor-driven oral cancer barrier module, which is an attempt to describe the pathogenesis of the disease and potential regulatory drugs from a global perspective. Functional disease modules were identified by constructing a protein-specific interaction network in patients' oral tissues. Then, comprehensive pathogenesis was explored through combination with analysis of functional and signaling pathway enrichment, prediction of key regulatory factors. It was found that these specifically expressed proteins and their interactions often play a pivotal part in oral tumors. This is reflected in the results of functional and pathway enrichment of modulating genes, which show that they are mainly involved in various immune responses, inflammatory reactions, oral plaque, and oral ulcer-related regulatory processes. This may represent the potential pathogenesis of oral tumors. On the predictive analysis of regulators, a series of ncRNAs (including miR-590, CRNDE and miR-340) and transcription factors (including E2F1, MYC and TP53) were identified that have potential important regulatory effects on oral tumors. These key regulators may manipulate a crucial part of the module sub-network and then work together to mediate the occurrence of oral tumors. On the comprehensive Multi-omics module analysis, the specific proteins and their interactions in patients' oral tissues were identified, while the prominent pivotal regulators were involved in the different pathogenic functions of oral tumors.