Explore the vast range of titles available.

Signaling via pattern recognition receptors (PRRs) expressed on professional antigen presenting cells, such as dendritic cells (DCs), is crucial to the fate of engulfed microbes. Among the many PRRs expressed by DCs are Toll-like receptors (TLRs) and C-type lectins such as DC-SIGN. DC-SIGN is targeted by several major human pathogens for immune-evasion, although its role in intracellular routing of pathogens to autophagosomes is poorly understood. Here we examined the role of DC-SIGN and TLRs in evasion of autophagy and survival of Porphyromonas gingivalis in human monocyte-derived DCs (MoDCs). We employed a panel of P. gingivalis isogenic fimbriae deficient strains with defined defects in Mfa-1 fimbriae, a DC-SIGN ligand, and FimA fimbriae, a TLR2 agonist. Our results show that DC-SIGN dependent uptake of Mfa1+P. gingivalis strains by MoDCs resulted in lower intracellular killing and higher intracellular content of P. gingivalis. Moreover, Mfa1+P. gingivalis was mostly contained within single membrane vesicles, where it survived intracellularly. Survival was decreased by activation of TLR2 and/or autophagy. Mfa1+P. gingivalis strain did not induce significant levels of Rab5, LC3-II, and LAMP1. In contrast, P. gingivalis uptake through a DC-SIGN independent manner was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores, a characteristic feature of autophagy. These results suggest that selective engagement of DC-SIGN by Mfa-1+P. gingivalis promotes evasion of antibacterial autophagy and lysosome fusion, resulting in intracellular persistence in myeloid DCs; however TLR2 activation can overcome autophagy evasion and pathogen persistence in DCs.

Objective To assess pain intensity levels during orthodontic therapy of Class II malocclusion patients undergoing skeletally anchored maxillary molar distalization assisted with different micro-osteoperforation (MOP) approaches. Methods Twenty-seven patients (12 males and 18 females) with a mean age of 16.1 ± 0.3 years were randomized into three equal groups (n=9): Group 1 comprised MOPs on buccal surface, Group 2 comprised MOPs on buccal and palatal surface, and Group 3 comprised the control or no-MOP group. The patients underwent maxillary molar distalization using skeletally anchored distal jet appliance assisted with or without MOPs. The MOPs were applied repeatedly on the buccal and buccal and palatal sides, or no MOP (control). Pain intensity was assessed using a 10 cm visual analog scale after each device activation at 24, 48, 72 hours, and at seven days. Data were analyzed using one-way ANOVA and repeated measures ANOVA for non-paired and paired means. Results Both approaches of buccal and buccal and palatal application of MOPs showed statistically significant (p< 0.01) higher levels of pain intensity after the first activation at 24 hours. Nevertheless, pain intensity levels decreased significantly in both MOP groups and between the two activations. Conclusion The repeated application of MOPs on either the buccal side only or on both buccal and palatal sides during maxillary molar distalization did not affect the levels of pain experienced; however, these levels were reported to be higher than that obtained in the control group. Moreover, it is observed that these pain levels tend to gradually reduce to mild levels over the subsequent days.

BackgroundApolipoprotein A1 and B and their ratio are considered a better biomarker for cardiovascular diseases than a lipid profile, but this previous finding is not proved to cerebrovascular ischemic diseases. The aim of this study is to assess the relation between apolipoprotien A1 and B and their ratio to intra- and extracranial carotid atherosclerosis in patients with ischemic acute stroke.Methods90 Egyptian patients with acute ischemic stroke are included in the study, and they have been classified into 3 groups: group 1 includes 30 patients with intracranial stenosis, group 2 includes 30 patients with extracranial arterial stenosis, and group 3 includes 30 patients with non-arterial stenosis. Patients were subjected to clinical assessment, routine laboratory measures, and Color-Coded Duplex Sonography for extracranial and intracranial arteries. The measurement of serum levels of apolipoproteins A1 and B was done using enzyme-linked immuno-sorbent assay (ELISA).ResultsA statistically significant difference was found between patient groups as regards the frequency of abnormal serum LDL-cholesterol (p = 0.04), being elevated in patients with extracranial stenosis (p = 0.01). There was a significant difference between patients groups as regards the frequency of abnormal serum HDL-cholesterol (p = 0.02), being lower in patients with extracranial stenosis. High Apo B/A1 ratio was an independent risk factor for intracranial arterial stenosis (p = 0.045). An abnormal elevation of serum LDL cholesterol was an independent risk factor of extracranial arterial stenosis (p = 0.021).ConclusionApo B/A1 ratio is an independent risk factor for intracranial arterial stenosis, while serum LDL cholesterol is an independent risk factor for extracranial arterial stenosis. Apo B/A1 ratio and serum LDL cholesterol are reliable serum biomarkers for cranial arterial stenosis in acute ischemic stroke patients.

Periodontitis is a disease of ageing or inflammaging, and is comorbid with other more severe age-related chronic diseases. With advanced age comes an increase in accumulation of senescent cells that release soluble and insoluble pro-inflammatory factors collectively termed the senescence associated secretory phenotype (SASP). In the present report, we examined whether immune cells typical of those at the oral mucosa-microbe interface, are vulnerable to cellular senescence (CS) and the role of dysbiotic oral pathogen Porphyromonas gingivalis . Bone marrow-derived dendritic cells (DCs) from young (yDCs) and old (oDCs) mice were co-cultured in vitro with CS inducer doxorubicin or P.gingivalis (Pg) , plus or minus senolytic agent rapamycin. CS profiling revealed elevated CS mediators SA-β-Gal, p16 INK4A , p53, and p21 Waf1/Clip1 in oDCs, or yDCs in response to doxorubicin or P. gingivalis , reversible with rapamycin. Functional studies indicate impaired maturation function of oDCs, and yDC exposed to P. gingivalis ; moreover, OVA-driven proliferation of CD4+ T cells from young OTII transgenic mice was impaired by oDCs or yDCs+Pg. The SASP of DCs, consisting of secreted exosomes and inflammasome-related cytokines was further analyzed. Exosomes of DCs cocultured with P. gingivalis (PgDCexo) were purified, quantitated and characterized. Though typical in terms of size, shape and phenotype, PgDCexo were 2-fold greater in number than control DCs, with several important distinctions. Namely, PgDCexo were enriched in age-related miRNAs, and miRNAs reported to disrupt immune homeostasis through negative regulation of apoptosis and autophagy functions. We further show that PgDCexo were enriched in P. gingivalis fimbrial adhesin protein mfa1 and in inflammasome related cytokines IL-1β, TNFα and IL-6. Functionally PgDCexo were readily endocytosed by recipient yDCs, amplifying functional impairment in maturation and ability to promote Ova-driven proliferation of OTII CD4+ T cells from young mice. In conclusion P. gingivalis induces premature (autocrine) senescence in DCs by direct cellular invasion and greatly amplifies senescence, in paracrine, of bystander DCs by secretion of inflammatory exosomes. The implications of this pathological pathway for periodontal disease in vivo is under investigation in mouse models.

Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4⁺ T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections.

Background This study aimed to delineate the clinical phenotype of patients with 9p deletions, pinpoint the chromosomal breakpoints, and identify the critical region for trigonocephaly, which is a frequent finding in 9p terminal deletion. Methods We investigated a cohort of nine patients with chromosome 9p terminal deletions who all displayed developmental delay, intellectual disability, hypotonia, and dysmorphic features. Of them, eight had trigonocephaly, seven had brain anomalies, seven had autistic manifestations, seven had fair hair, and six had a congenital heart defect (CHD). Results Karyotyping revealed 9p terminal deletion in all patients, and patients 8 and 9 had additional duplication of other chromosomal segments. We used six bacterial artificial chromosome (BAC) clones that could identify the breakpoints at 17–20 Mb from the 9p terminus. Array CGH identified the precise extent of the deletion in six patients; the deleted regions ranged from 16 to 18.8 Mb in four patients, patient 8 had an 11.58 Mb deletion and patient 9 had a 2.3 Mb deletion. Conclusion The gene deletion in the 9p24 region was insufficient to cause ambiguous genitalia because six of the nine patients had normal genitalia. We suggest that the critical region for trigonocephaly lies between 11,575 and 11,587 Mb from the chromosome 9p terminus. To the best of our knowledge, this is the minimal critical region reported for trigonocephaly in 9p deletion syndrome, and it warrants further delineation. Nine patients with chromosome 9p terminal deletion presented with developmental delay, intellectual disability, and dysmorphic features. We concluded that the deletion of the genes in the 9p24 region are not sufficient to cause ambiguous genitalia as six out of our nine patients had normal genitalia. Based on our study we suggested that the critical region for trigonocephaly may lies within 11.8 kb in 9p23 cytoband.

Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.

(1) Background: The aim of this study was to test whether matrix-bound zoledronate (zol) molecules enhanced the oral biofilm colonization of a mineralized matrix, rendering the alveolar bone more susceptible to medication-related osteonecrosis of the jaw (MRONJ) following invasive dental procedures. (2) Methods: We tested the effect of matrix-bound zol on the growth and attachment of Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn) and Actinomyces israelii (Ai), and whether the nitrogen-containing component of zol contributed to such effect. The role of oral bacteria in the induction of osteonecrosis was then tested using an extra-oral bone defect model. (3) Results: The attachment of biofilm to hydroxyapatite discs increased when the discs were pre-treated with zol. Bacterial proliferation was not affected. Matrix-bound zol was more potent than non-nitrogen-containing etidronate in enhancing the colonization. Stimulation was dampened by pre-treating the bacteria with histidine. The delivery of oral biofilm to a tibial defect caused osteonecrosis in zol-treated rats. (4) Conclusions: We conclude that matrix-bound zol enhances the oral biofilm colonization of hydroxyapatite. This enhancement depended on the presence of the nitrogen-containing group. The oral biofilm rendered the extra-oral bone susceptible to medication-related osteonecrosis, suggesting that it has an important role in the induction of MRONJ.

Background Thyroid dysfunction is a worldwide phenomenon in women, and the prevalence increases during pregnancy, with hypothyroidism being the most common. In most developing countries, nutritional deficiencies of nearly all essential nutrients, including iron, vitamin B12, and folic acid, are common in pregnant women. Thyroid disorders and nutritional deficiencies especially of iron and vitamin B12 cause a number of maternofetal complications. Objectives To assess thyroid status in pregnant Saudi women and explore its relation to ferritin and vitamin B12. Patients and methods This was a cross-sectional study conducted at antenatal clinics of the Northern Area Armed Forces Hospital, KSA, enrolling 254 Saudi women: 180 pregnant [classified according to gestational age into group A (first trimester) and group B (second trimester)], and 74 age-matched healthy nonpregnant women, as control group (group C). After a detailed obstetrical and medical history, and clinical assessment, participants were subjected to laboratory investigations in the form of thyroid function by measuring thyroid-stimulating hormone (TSH) and free thyroxin, hemoglobin (HB), serum ferritin, and vitamin B12 levels. Results TSH level was lower in pregnant than nonpregnant women. Subclinical hypothyroidism (35.5%) was the most common thyroid disorder followed by overt hypothyroidism (10%) and hypothyroxinemia (2.2%) in pregnant women. HB and vitamin B12 levels were significantly lower in first and second trimesters of pregnancy when compared with controls ( P =0.001). Serum free thyroxin correlated positively with HB and ferritin, whereas TSH correlated negatively with HB and ferritin. Conclusion High prevalence of hypothyroidism in pregnant females and its association with iron and vitamin B12 deficiencies highlight the urgent need for thyroid status to be detected and to evaluate nutritional deficiencies in such group, so as to start early treatment promptly and to prevent the adverse effects of the disorder to both mother and fetus to achieve normal pregnancy outcome.

The practical usage of untraditional feedstuffs such as sunflower meal (SFM) in laying hens nutrition in developing countries has received considerable attention. SFM is a by-product of the sunflower oil industry and has been progressively added to bird’s diets. Sunflower meal (SFM) is gaining great interest as a feed ingredient due to its eminent crude protein content, low anti-nutritional compounds, and low price. The current experiment was aimed to assess the production efficiency, egg quality, yolk fatty acids composition, and nutrient digestibility of laying hens fed SFM. A total of 162 Bovans Brown laying hens aged 60 weeks old were randomly allocated using a completely randomized design into three experimental groups of nine replicates each (n = six/replicate) for eight weeks. The dietary treatments involved a control (basal diet) and two levels of SFM, 50 and 100 g/kg feed. The dietary treatments did not influence live weight gain, feed intake, and egg mass. On one hand, the laying rate was increased; on the other hand, the feed conversion ratio and broken eggs rate of laying hens were decreased (p < 0.05) by the dietary inclusion of SFM. Dietary treatments had no effect on the egg’s quality characteristics except the yolk color and yolk height were larger (p = 0.01) for laying hens fed SFM compared with those fed the control. Dietary inclusion of SFM decreased (p < 0.05) the content of cholesterol in the egg yolk. Still, it increased the yolk contents of vitamin E, calcium, linoleic acid, linolenic acid, and oleic acid (p < 0.05). Furthermore, the dietary inclusion of SFM increased crude protein and calcium digestibility, but decreased the ether extract digestibility. In conclusion, our results suggested that the dietary inclusion of SFM, up to 100 g/kg at a late phase of laying, could improve the production performance, some of the egg quality traits, and nutrient digestibility while decreasing egg yolk cholesterol.