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The article focuses on the diagnosis of an Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) in a patient with psoriatic arthritis. Topics include the clinical presentation of the ulcerative lesion, diagnostic findings from biopsy and immunohistochemistry, and the resolution of the condition following treatment.

The article focuses on evaluating the high frequency of stromal myofibroblasts in odontogenic keratocysts (OKCs) associated with an impacted tooth compared to other odontogenic cysts and pericoronal follicles (PFs). It highlights that OKCs associated with impacted teeth (OKC-a) exhibit a significantly higher number of α-SMA positive cells than those not associated with impacted teeth (OKC-na) and dentigerous cysts (DCs).

The main risk factor for chronic obstructive pulmonary disease (COPD) is cigarette smoke (CS). It can alter many immune cells functions such as phagocytosis, efferocytosis and cytokine production. Cytokines play a role in the orchestration of inflammation in COPD. The JAK/STAT pathways are among the most important signalling components of cytokines. The objective of this work was to investigate the role of the JAK/STAT pathway with regard to cytokine release and microsphere uptake capacity (to minimize the non‐specific scavenging) in human monocyte‐derived‐macrophages (MDMs). The MDMs were stimulated by cigarette smoke extract (CSE) alone or in combination with lipopolysaccharide (LPS). CSE alone was not associated with significant changes in the cytokine, with the exception of IL‐8/CXCL8 production. However, CSE disturbed cytokine production in LPS‐stimulated MDMs. CSE increase CXCL‐8 and CCL2 release in LPS‐stimulated monocyte‐derived macrophages and suppressed the production of IL‐6 and CXCL1 in these cells. CSE also decreased microsphere uptake capacity by MDMs. Then, CSE + LPS‐stimulated MDMs were treated with two different JAK inhibitors. AG490 (specific inhibitor of JAK2) and ruxolitinib (inhibitor of JAK1 and JAK2). JAK/STAT inhibitors, particularly ruxolitinib, attenuated in cytokine production without completely inhibiting when compared with dexamethasone. On the other hand, the cells exposed to dexamethasone are nearly unable to capture the microspheres, while both JAK inhibitors do not affect the uptake capacity. In summary, our results showed the versatility of ruxolitinib which might bring a better balance disturbance of cytokine release and uptake capacity. The information regarding the distinctive effect of JAK/STAT inhibitors may be useful in the development of novel treatments for COPD. [ABSTRACT FROM AUTHOR]

Xanthomas are microscopically characterized by localized infiltrates of lipid-laden macrophages, usually on the skin and mucosal surfaces (respiratory and gastrointestinal tracts).1-8 Cutaneous xanthoma in particular may represent a localized idiopathic phenomenon or systemic hyperlipidemia.3 While several types of cutaneous xanthomas have been described in the literature,1,2 those affecting the respiratory and gastrointestinal tracts are usually named "xanthomas."3-8 Recent studies have also reported xanthomas at intraosseous locations, affecting the jaws.9-11 Interestingly, xanthomas, as described in the respiratory and gastrointestinal tracts,3-8 have not been reported in the oral mucosa. Microscopic examination (H&E stain) revealed exuberant foam cell proliferation in the superficial part, permeated by lymphomononuclear infiltrate (B, ×100; C, ×400). JXG is a histiocytic disorder with frequent cutaneous involvement.14-16 Microscopically, JXG exhibits a proliferation of histiocytes with a foamy, eosinophilic, and vacuolated cytoplasm, often admixed with Touton-type giant cells. Microscopic examination revealed exuberant foam cell proliferation, with foci of lymphomononuclear infiltrate, in close contact with normal-appearing surface squamous epithelium. [Extracted from the article]

A growing body of experimental evidence shows that glycinergic inhibition plays vital roles in spinal pain processing. In spite of this, however, our knowledge about the morphology, neurochemical characteristics, and synaptic relations of glycinergic neurons in the spinal dorsal horn is very limited. The lack of this knowledge makes our understanding about the specific contribution of glycinergic neurons to spinal pain processing quite vague. Here we investigated the morphology and neurochemical characteristics of glycinergic neurons in laminae I–IV of the spinal dorsal horn using a GlyT2::CreERT2‐tdTomato transgenic mouse line. Confirming previous reports, we show that glycinergic neurons are sparsely distributed in laminae I–II, but their densities are much higher in lamina III and especially in lamina IV. First in the literature, we provide experimental evidence indicating that in addition to neurons in which glycine colocalizes with GABA, there are glycinergic neurons in laminae I–II that do not express GABA and can thus be referred to as glycine‐only neurons. According to the shape and size of cell bodies and dendritic morphology, we divided the tdTomato‐labeled glycinergic neurons into three and six morphological groups in laminae I–II and laminae III–IV, respectively. We also demonstrate that most of the glycinergic neurons co‐express neuronal nitric oxide synthase, parvalbumin, the receptor tyrosine kinase RET, and the retinoic acid‐related orphan nuclear receptor β (RORβ), but there might be others that need further neurochemical characterization. The present findings may foster our understanding about the contribution of glycinergic inhibition to spinal pain processing. [ABSTRACT FROM AUTHOR]

Background: Despite advances in cancer diagnosis and therapeutics, the overall 5‐year survival rate of oral squamous cell carcinoma (OSCC) remains low. Tumor formation, progression, recurrence, and chemo‐resistance are associated with the presence of cancer stem cells (CSC) that show phenotypic heterogeneity, but how they influence tumor behavior remains poorly understood. We aimed to describe how two CSC phenotypes from an OSCC cell line, CD44HighESAHigh (Epi‐CSC) and CD44HighESALow (EMT‐CSC), behave in vitro and in vivo. Methods: In vitro behavior of FACS‐sorted Epi‐CSC and EMT‐CSC from OSCC cells was characterized by their ability to form colonies, migrate, proliferate, and to invade a solid matrix. In vivo experiments were conducted in immunodeficient (NOD/SCID) mice by orthotopic xenografting of FACS‐sorted OSCC subpopulations. Results: In vitro, the Epi‐CSC phenotype was more proliferative and generated more holoclones than the EMT phenotype. On the other hand, EMT‐CSC migrate and invaded more than Epi‐CSC cells in 3D culture, suggesting the CSC phenotype affects tumor cell behavior. When inoculated orthotopically into the tongues of immunodeficient mice, both subpopulations generated OSCC, but EMT‐CSC formed fewer and smaller tumors. Conclusions: Our results suggest that while cells in the Epi‐CSC form the subpopulation that enables tumor growth, the EMT‐CSC are related to migration and invasion. Clinically, this may reflect the importance of Epi‐CSC for tumorigenesis and of the EMT‐CSC for metastasis and highlights that variation in the proportion of CSC phenotypes from patient to patient may be relevant to the design of individual treatment protocols. [ABSTRACT FROM AUTHOR]

Background: Exercise is a powerful tool for prevention and treatment of many conditions related to the cardiovascular system and also chronic low‐grade inflammation. Peroxisome proliferator‐activated receptors γ (PPARγ) exerts an import role on the regulation of metabolic profile and subsequent inflammatory response, especially in macrophages. Purpose: To investigate the effects of 8‐week moderate‐exercise training on metabolic and inflammatory parameters in mice with PPARγ deficiency in myeloid cells. Methods: Twelve‐week old mice bearing PPARγ deletion exclusively in myeloid cells (PPARγlox/lox Lys Cre −/+, knockout [KO]) and littermate controls (PPARγlox/lox Lys Cre −/−, wild type [WT]) were submitted to 8‐week exercise training (treadmill running at moderate intensity, 5 days/week). Animals were evaluated for food intake, glucose homeostasis, serum metabolites, adipose tissue and peritoneal macrophage inflammation, and basal and stimulated cytokine secretion. Results: Exercise protocol did not improve glucose metabolism or adiponectin concentrations in serum of KO mice. Moreover, the absence of PPARγ in macrophages exacerbated the proinflammatory profile in sedentary mice. Peritoneal cultured cells had higher tumor necrosis factor‐α (TNF‐α) secretion in nonstimulated and lipopolysaccharide (LPS)‐stimulated conditions and higher Toll‐4 receptor (TLR4) gene expression under LPS stimulus. Trained mice showed reduced TNF‐α content in adipose tissue independently of the genotype. M2 polarization ability was impaired in KO peritoneal macrophages after exercise training, while adipose tissue‐associated macrophages did not present any effect by PPARγ ablation. Conclusion: Overall, PPARγ seems necessary to maintain macrophages appropriate response to inflammatory stimulus and macrophage polarization, affecting also whole body lipid metabolism and adiponectin profile. Exercise training showed as an efficient mechanism to restore the immune response impaired by PPARγ deletion in macrophages. PPARγ seems to maintain macrophages appropriate response to inflammatory stimulus and macrophage polarization. Exercise training was an efficient mechanism to restore the immune response impaired by PPARγ deletion in macrophages. [ABSTRACT FROM AUTHOR]

The regenerative capacity of CNS tracts has ever been a great hurdle to regenerative medicine. Although recent studies have described strategies to stimulate retinal ganglion cells (RGCs) to regenerate axons through the optic nerve, it still remains to be elucidated how these therapies modulate the inhibitory environment of CNS. Thus, the present work investigated the environmental content of the repulsive axon guidance cues, such as Sema3D and its receptors, myelin debris, and astrogliosis, within the regenerating optic nerve of mice submitted to intraocular inflammation + cAMP combined to conditional deletion of PTEN in RGC after optic nerve crush. We show here that treatment was able to promote axonal regeneration through the optic nerve and reach visual targets at twelve weeks after injury. The Regenerating group presented reduced MBP levels, increased microglia/macrophage number, and reduced astrocyte reactivity and CSPG content following optic nerve injury. In addition, Sema3D content and its receptors are reduced in the Regenerating group. Together, our results provide, for the first time, evidence that several regenerative repulsive signals are reduced in regenerating optic nerve fibers following a combined therapy. Therefore, the treatment used made the CNS microenvironment more permissive to regeneration. [ABSTRACT FROM AUTHOR]

Background: There are few randomized, controlled clinical trials about the effect of non-surgical periodontal treatment on oral health-related quality of life (OHRQL). This study aims to compare the effects of two different forms of non-surgical periodontal therapy, scaling and root planing (SRP) per quadrant and one-stage full-mouth disinfection (FMD), on periodontal clinical parameters and OHRQL of patients with chronic periodontitis.Methods: In this randomized, controlled clinical trial, the questionnaires Oral Impacts on Daily Performance (OIDP) and Oral Health and Quality of Life (OHQoL) were given to 90 patients divided into two groups: SRP (n = 45) and FMD (n = 45). Periodontal clinical parameters recorded included probing depth, clinical attachment level, plaque index, and gingival index. For statistical analysis, χ(2) test, Fisher exact test, Mann-Whitney U test, and Wilcoxon test were used. Intention-to-treat analyses were performed at T0 (baseline) for periodontal clinical parameters, T1 (30 days after treatment) for questionnaires, and T2 (180 days after treatment) for both.Results: No significant differences were identified between the SRP and FMD groups in regard to OHQoL and OIDP scores when comparing the data of T1 and T2.Conclusion: Patients treated by both SRP and FMD showed improvement in all periodontal clinical parameters and OHRQL, with no significant differences between treatment groups. [ABSTRACT FROM AUTHOR]

Aim: To relate the clinical effects of two different forms of non-surgical periodontal therapy -- scaling and root planing per quadrant (SRP-Q) and one-stage full-mouth disinfection (FMD) -- to patient-based outcomes such as fear, anxiety, and pain of moderate chronic periodontitis patients. Methods: Dental Fear Survey (DFS) and Dental Anxiety Scale (DAS) questionnaires and Visual Analogue Scale (VAS) were applied to 78 patients randomized into two groups: SRP-Q (n = 37) and FMD (n = 41). Periodontal clinical parameters: probing pocket depth (PD), clinical attachment level (CAL), plaque index (PI), and gingival index (GI) were monitored at baseline and 6 months after treatment. Data were statistically analysed by chi-square, Fisher's exact, Mann-Whitney, Wilcoxon tests, Pearson's correlation, and Cluster analysis. Results: All periodontal clinical parameters improved from baseline to 6 months. Patients with higher fear and anxiety showed a worse clinical periodontal status before and after treatment (mean CAL, PI, and GI). After both types of treatment, fear and anxiety decreased (FMD: p = 0.019; SRP-Q: p = 0.043) with no differences between the groups. Pain did not differ between groups (FMD: 20.6 ± 19.0 and SRP: 20.7 ± 20.0; p = 0.930). Conclusions: In moderate chronic periodontitis patients, SRP-Q and FMD provided periodontal clinical improvements and similar experiences of fear, anxiety, and pain. [ABSTRACT FROM AUTHOR]

In order to evaluate whether ovarian volume, presence and diameter of the corpus luteum ( CL) have effects on the number and quality of bovine recovered oocytes, 110 ovaries were obtained from the slaughterhouse. Cumulus oocytes complex were aspirated and evaluated under stereomicroscope. Oocytes were counted and classified according to their quality (Grades I, II, III and IV). Ovarian volume was weakly correlated to the number of good quality oocytes ( P < 0.05). Ovaries with CL showed greater numbers of good quality oocytes than ovaries without CL ( P < 0.05). Further, presence of CL and its diameter positively influenced the probability of recovering good quality oocytes ( P < 0.05). In conclusion, ovarian volume is not a good parameter itself to predict important ovarian characteristics; moreover, analysis of CL, its presence and diameter, may be a good tool to improve efficiency on in vitro embryo production programs. [ABSTRACT FROM AUTHOR]

Theaimof this study was to evaluate the effects of vitamin E associated with rapid thawing on cryopreserved goat semen. Two bucks were used and eight ejaculates per animal were collected using artificial vagina. Semen was diluted with the following treatments: BIOXCELL (control), BIOXCELL + Equex (sodiumlauryl sulphate) and BIOXCELL + vitamin E 100 μM. Semen was packaged into 0.25mL straws and cooled at 5°C for 1 hour. Freezing was performed in liquid nitrogen vapor (-155°C) during 15minutes.Then, the straws were immersed in liquid nitrogen (-196°C). Straws were thawed at 38°C/60 seconds or at 60°C/7 seconds with immediate spermanalysis.Hypoosmotic swelling test was performed adding a 20 μL aliquot of thawed semen to 1mL of hypoosmotic solution (100 mOsm·Kg-1) followed by incubation during 60 minutes in water bath (38°C). Vitamin E did not affect any studied parameters (P > 0.05). Nevertheless, defrosting rate of 60°C/7 seconds improved sperm membrane functional integrity (P < 0.05). Current knowledge about goat semen cryopreservation is not sufficient to ensure high post-thawing recovery rates; thus, this study brings important data about using antioxidants and different thawing rates on cryopreservation process. [ABSTRACT FROM AUTHOR]

Few studies have investigated liver gluconeogenesis in cancer and there is no agreement as to whether the activity of this pathway is increased or decreased in this disease. The aim of this study was to evaluate gluconeogenesis from alanine, pyruvate and glycerol, and related metabolic parameters in perfused liver from Walker-256 tumour-bearing rats on days 5 ( WK5 group), 8 ( WK8 group) and 12 ( WK12 group) of tumour development. There was reduction ( P < 0.05) of liver glucose production from alanine and pyruvate in WK5, WK8 and WK12 groups, which was accompanied by a decrease ( P < 0.05) in oxygen consumption. Moreover, there was higher ( P < 0.05) pyruvate and lactate production from alanine in the WK5 group and a marked reduction ( P < 0.05) of pyruvate and urea production from alanine in the WK12 group. In addition, liver glucose production and oxygen consumption from glycerol were not reduced in WK5, WK8 and WK12 groups. Thus the, the results show inhibition of hepatic gluconeogenesis from alanine and pyruvate, but not from glycerol, on days 5, 8 and 12 of Walker-256 tumour development, which can be attributed to the metabolic step in which the substrate enters the gluconeogenic pathway. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2012) 41: 54-60 Background: Oral cancer overexpressed 1 ( ORAOV1) was found as a candidate oncogene in the 11q13 chromosomal region, based on its amplification and overexpression in oral cancer cell lines. Because gene amplification often leads to increased levels of gene expression, we aimed to verify the relationship between ORAOV1 gene status and mRNA expression primarily in oral squamous cell carcinoma (OSCC) by quantitative assay, correlating with clinical and pathological characteristics in patients. Methods: Levels of ORAOV1 amplification and expression were evaluated by qPCR and RT-qPCR in OSCC cell lines and in tumor and non-tumoral surgical margins from 33 patients with OSCC. All subjects were smokers and habitual alcohol drinkers, mostly men above 40 years of age and with a single primary tumor. Results: ORAOV1 exhibited increased gene expression levels as well as higher copy number in three OSCC cell lines with 11q13 amplified chromosomal region when compared with the OSCC cell line without the amplification (one-way ANOVA, P < 0.05). Weak correlation between ORAOV1 mRNA levels and DNA copy number was seen in tumor samples (Spearman, P = 0.07). Although ORAOV1 was amplified in tumor (Wilcoxon, P < 0.01), high levels of transcripts in margin did not reveal differences in comparison with tumor (Wilcoxon, P = 0.85). Aggressiveness and survival rate did not demonstrate statistical difference for both events in OSCC. Conclusion: The overexpression of ORAOV1 in non-tumoral margin samples can occur in the absence of amplification. The weak correlation between ORAOV1 amplification and expression in OSSC suggests that ORAOV1 expression can be regulated by mechanisms other than gene amplification. [ABSTRACT FROM AUTHOR]

Background: This study aims to analyze the relationship between chronic periodontitis and C-reactive protein (CRP) by considering associated variables in individuals with or without cardiovascular disease. Methods: A sample of 359 individuals of both sexes (aged ≥40 years) was assessed. Among these individuals, 144 subjects were admitted to the hospital because of a first occurrence of acute myocardial infarction; 80 subjects were in the hospital for reasons other than acute myocardial infarction; and 135 subjects were living in the community. A questionnaire was applied to obtain demographic and lifestyle characteristics. Complete clinical periodontal examinations and anthropometric assessments were performed. CRP levels, plasma glucose levels, lipid profiles, and blood tests were performed to investigate any conditions that might have suggested infection and/or inflammation. CRP evaluations were performed using nephelometry. Individuals were considered to have periodontal disease if they simultaneously presented at least four teeth with one or more sites with probing depth ≥4 mm, clinical attachment loss ≥3 mm, and bleeding on probing. Procedures for descriptive analyses and logistic regression were used. Results: In the chronic periodontitis group, mean CRP levels were higher than those in the group without chronic periodontitis (2.6 ± 2.6 mg/L versus 1.78 ± 2.7 mg/L, respectively). The final model showed that individuals with chronic periodontitis were more likely to have high CRP levels (adjusted odds ratio: 2.26; 95% confidence interval: 1.30 to 3.93) considering the effects of age, schooling level, sex, smoking, high-density lipoprotein cholesterol, and diabetes. Conclusion: In this study, chronic periodontitis is associated with elevated plasma CRP levels, even after controlling for several potential confounders. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, strong evidence for an association between maternal periodontitis and low birthweight has started to appear. However, few intervention studies have been proposed for investigating this hypothesis. The aim of this study was to evaluate whether periodontal therapy among pregnant women would reduce the incidence of low birthweight. Methods: A nonrandomized intervention study was performed, with two control groups. The sample comprised 339 pregnant women: 141 in the experimental group (treated for periodontitis), 145 in control group 1 (without periodontitis) and 53 in control group 2 (with untreated periodontitis). The experimental group received periodontal treatment throughout pregnancy, whereas control group 1 was only monitored over the same period. After delivery, birthweight information on the newborns was obtained. The analysis procedures consisted of stratified analysis followed by logistic regression. Results: The frequency of low birthweight among the women with treated periodontitis was 9.22%, while it was 13.10% in the group without periodontal disease. However, the difference was not statistically significant (RR 0.72; 95% CI 0.36–1.45). The occurrence of this outcome in the group with untreated periodontitis (24.53%) was greater than in the other two groups. Conclusion: This suggests that periodontal therapy is a protective factor for birthweight. [ABSTRACT FROM AUTHOR]

Background: Oncogenic Wnt/β-catenin signaling occurs in numerous types of cancers, but little is known about the role of the Wnt protein family member, WNT-5A, in lip carcinogenesis. The aim of this study was to investigate WNT-5A, β-catenin, and matrix metalloproteinase (MMP)-3 protein expression in actinic cheilitis (AC), and lip squamous cell carcinoma (LSCC). Methods: Twenty-one cases of AC, and fifty-one cases of LSCC were analyzed, with normal lip mucosa used as a control. Qualitative and semi-quantitative analyses of WNT-5A, β-catenin, and MMP-3 immunostaining pattern and cellular distribution were performed. Results: WNT-5A was observed in more than 50% of the cells, scattered in all layers of AC, in contrast to the absence of immunostaining in normal lip mucosa. AC presented a higher level of WNT-5A expression than LSCC ( P = 0.0289, Fisher test), while MMP-3 immunoexpression was statistically more significant in LSCC than in AC ( P = 0.0285, Fisher test). Immunolabeling of β-catenin protein was differentially distributed between samples; the majority of AC cases (61.90%) demonstrated a membranous-cytoplasmic pattern, while a considerable number of LSCC cases (29.41%) revealed a cytoplasmic pattern, instead of the usual membranous pattern. Conclusions: The present results suggest that WNT-5A may be an important marker during initial events of AC malignant transformation, in which non-canonical and canonical Wnt/β-catenin signaling pathways could be involved. Additionally, WNT-5A might recruit other events in LSCC, such as MMP-3 protein synthesis, as its presence is increased in established malignant processes without β-catenin dependency. [ABSTRACT FROM AUTHOR]

Background: Oncogenic Wnt/beta-catenin signaling occurs in numerous types of cancers, but little is known about the role of the Wnt protein family member, WNT-5A, in lip carcinogenesis. The aim of this study was to investigate WNT-5A, beta-catenin, and matrix metalloproteinase (MMP)-3 protein expression in actinic cheilitis (AC), and lip squamous cell carcinoma (LSCC). Methods: Twenty-one cases of AC, and fifty-one cases of LSCC were analyzed, with normal lip mucosa used as a control. Qualitative and semi-quantitative analyses of WNT-5A, beta-catenin, and MMP-3 immunostaining pattern and cellular distribution were performed. Results: WNT-5A was observed in more than 50% of the cells, scattered in all layers of AC, in contrast to the absence of immunostaining in normal lip mucosa. AC presented a higher level of WNT-5A expression than LSCC (P = 0.0289, Fisher test), while MMP-3 immunoexpression was statistically more significant in LSCC than in AC (P = 0.0285, Fisher test). Immunolabeling of beta-catenin protein was differentially distributed between samples; the majority of AC cases (61.90%) demonstrated a membranous-cytoplasmic pattern, while a considerable number of LSCC cases (29.41%) revealed a cytoplasmic pattern, instead of the usual membranous pattern. Conclusions: The present results suggest that WNT-5A may be an important marker during initial events of AC malignant transformation, in which non-canonical and canonical Wnt/beta-catenin signaling pathways could be involved. Additionally, WNT-5A might recruit other events in LSCC, such as MMP-3 protein synthesis, as its presence is increased in established malignant processes without beta-catenin dependency. [ABSTRACT FROM AUTHOR]

Background: Limited information is available regarding the attached keratinized tissue, probing depth, and sociodemographic characteristics of primary teeth. This study was carried out to evaluate the relationship among age, gender, race, gingival width, and probing depth in each primary tooth type. Methods: The study population consisted of 300 children, aged 4 to 6 years, with clinically healthy gingiva, who were enrolled in an oral health program. Gingival width and probing depth were measured with a standard Williams periodontal probe in the middle of the keratinized gingiva and at six gingival sites (mesio-buccal, mid-buccal, disto-buccal, mesio-lingual, mid-lingual, and disto-lingual), respectively. Schiller's solution was used to establish the limits of keratinized gingiva. Results: The gingival width (mean ± SD) on the buccal surfaces decreased from anterior to posterior positions in both arches; in the lower lingual surfaces, the inverse was observed. The gingival width (mean ± SD) ranged from 2.95 ± 0.15 mm to 6.16 ± 0.20 mm and the probing depth from 1.03 ± 0.91 mm to 2.08 ± 0.07 mm. There was a tendency toward increased probing depth as age increased from 4 to 6 years. There was also an increase in the probing depth from anterior to posterior teeth. Conclusions: In the majority of observations, it was concluded that there was a relationship among age, gingival width, and probing depth, but generally not among race and gender and these measurements, respectively. Furthermore, there is no relation between gender and gingival width and race and probing depth. [ABSTRACT FROM AUTHOR]

Proper hyphal morphogenesis is essential for the establishment and progression of invasive disease caused by filamentous fungi. In the human pathogen Aspergillus fumigatus, signalling cascades driven by Ras and Ras‐like proteins orchestrate a wide variety of cellular processes required for hyphal growth. For activation, these proteins require interactions with Ras‐subfamily‐specific guanine nucleotide exchange factors (RasGEFs). Although Ras‐protein networks are essential for virulence in all pathogenic fungi, the importance of RasGEF proteins is largely unexplored. A. fumigatus encodes four putative RasGEFs that represent three separate classes of RasGEF proteins (SH3‐, Ras guanyl nucleotide‐releasing protein [RasGRP]–, and LTE‐class), each with fungus‐specific attributes. Here, we show that the SH3‐class and RasGRP‐class RasGEFs are required for properly timed polarity establishment during early growth and branch emergence as well as for cell wall stability. Further, we show that SH3‐class RasGEF activity is essential for polarity establishment and maintenance, a phenotype that is, at least, partially independent of the major A. fumigatus Ras proteins, RasA and RasB. Finally, loss of both SH3‐class RasGEFs resulted in avirulence in multiple models of invasive aspergillosis. Together, our findings suggest that RasGEF activity is essential for the integration of multiple signalling networks to drive invasive growth in A. fumigatus. [ABSTRACT FROM AUTHOR]