Adult Gland Research Articles

Crinkled employs wingless pathway for wing development in Tribolium castaneum.

Crinkled is associated with embryonic denticle formation and auditory organ development in Drosophila melanogaster. However, the functions of Crinkled have not been fully investigated. Additionally, the genes that participate in the Crinkled pathway are unknown. Phylogenetic analysis indicates that crinkled exhibits a one-to-one orthologous relationship in insects. In Tribolium castaneum, the crinkled gene is 6,498bp in length and consists of six exons. Crinkled expression peaked during two phases in Tribolium: late embryonic and pupal stages. High levels of crinkled mRNA were detected in the fat body, head, epidermis, ovary, and accessory gland of late adults. Knockdown of crinkled using RNA interference (RNAi) severely affected wing morphogenesis in T. castaneum. We further showed that crinkled silencing reduced forked expression through wingless and shaven-baby, and RNAi of forked phenocopied the effects of crinkled knockdown in T. castaneum. This study investigated the development role of crinkled in postembryonic stages and indicated that forked mediates the functions of crinkled during wing morphogenesis in T. castaneum.

Post-weaning xenohormone intake affects adult rat submandibular gland in a sex-dependent manner.

We previously reported that maternal exposure to genistein and vinclozolin, ingested alone or in combination, affects submandibular salivary glands of rat offspring. Here, we investigated the responsiveness of submandibular gland when such xenohormone exposure occurs later in life. Chemicals were given orally to male and female Wistar rats (1mg/kg body weight per day), from weaning to adulthood. Submandibular glands and plasma were collected at postnatal day 100 for histologic and molecular analysis. Whereas no effect was observed in females, increases in granular convoluted tubules area coupled with a modification of salivary secretions were found in male submandibular glands. Genistein and vinclozolin similarly increased the mRNA expression of Cystatin C, Mucin 10, Growth factors, and plasmatic EGF. Negative correlations were found between the expressions of androgen receptor and EGF (-0.34; p<0.05), TGFα (-0.52; p<0.01), Mucin 10 (-0.43; p<0.05), and Cystatin C (-0.42; p<0.05) as well as between progesterone receptor and EGF (-0.56; p<0.01). The Spearman correlation test revealed also a positive correlation between salivary EGF-mRNA expression and EGF in plasma (+0.32; p<0.05). Our findings confirm the sex-dependent sensitivity of submandibular salivary glands to dietary xenohormones and underline the influence of the exposure period.

Host and environmental factors influencing 'Candidatus Liberibacter asiaticus' acquisition in Diaphorina citri.

Diaphorina citri is a vector of 'Candidatus Liberibacter asiaticus' (CLas) associated with citrus Huanglongbing. In this study, the infection and titers of CLas in the psyllid, were monitored for life cycle stage, sex, host-plant CLas titer, host-plant genotype, and ambient temperature. Acquisition efficiency of CLas by D. citri was highest in nymphs reared at 25 °C on a host plant with high CLas titers but was independent of the host genotypes assessed and of vector sex. We further observed that D. citri nymphs acquired CLas more rapidly than adults based on acquisition access periods (AAPs). CLas did not multiply in the alimentary canal, hemolymph, and salivary glands of adults for 18 days after a 3-day AAP as adult. However, CLas multiplication was detected in hemolymph and salivary gland of adults after the bacterium was acquired by nymphs. Eighty percent of salivary glands of adults contained CLas 18 days after a 3-day AAP as nymph compared to 10% 18 days after a 3-day AAP as adults. Different factors tested herein influenced CLas acquisition efficiency of D. citri, CLas multiplication and spread inside the psyllid. These observations serve to better understand mechanisms of CLas infection in D. citri. © 2018 Society of Chemical Industry.

Extracapsular extension is not a significant prognostic indicator in non-squamous cancers of the major salivary glands

BackgroundExtracapsular extension (ECE) is a well-established prognostic feature in squamous cell cancers of the head and neck. Although some extrapolate data from mucosal head and neck cancer to include ECE as a high-risk feature in salivary gland cancers, data is lacking about ECE’s prognostic value for these malignancies. We investigate whether ECE is a significant prognostic indicator in pathologic node-positive cancers of the major salivary glands.MethodsA retrospective study of adult salivary gland cancer cases diagnosed from 2004 to 2013 in the NCDB was conducted. Demographic, tumor, treatment, and survival variables were included in the study. Univariate Kaplan-Meier analyses, as well as multivariate Cox survival regressions were performed.ResultsPositive ECE status was associated with significantly worse survival in salivary SCC (HR 1.687; p = 0.002) but not non-squamous salivary cancers (HR 1.000; p = 0.998) on multivariate analysis. While post-operative radiotherapy was not associated with improved survival for patients without high-risk adverse features (high grade or positive surgical margins), its use was associated with better survival for ECE-positive salivary SCC patients without one of these additional adverse features (HR 0.064; p = 0.010).ConclusionsAlthough ECE is a significant prognostic indicator in salivary SCC, its prognostic significance for non-squamous salivary cancers may be limited. Radiotherapy may improve survival in cases with at least one high-risk adverse feature: high grade; positive surgical margins; and for salivary SCC specifically, positive ECE status.

Sex Difference in the Morphology of Pineal Gland in Adults Based on Brain Magnetic Resonance Imaging.

We aimed to figure out the anatomical features of pineal gland region on magnetic resonance imaging (MRI) and to explore the sex difference in pineal gland-related parameters with increasing age. We measured the pineal gland on MRI images from 198 healthy adults (96 males and 102 females). Included subjects were divided into 4 age groups. After 3-dimensional reconstruction, the anatomic features of pineal gland and its distances to superior colliculus and splenium of corpus callosum were analyzed in each group. The prevalence of cystic pineal gland was calculated. Moreover, we calculated the volume of pineal gland (PGV) and explored the differences of PGV in males and females across different age groups. Linear regression analysis was performed to detect the relationship between age and pineal gland-related parameters. In 198 subjects, the mean length, width, and height of pineal gland were 7.58 ± 0.45 mm, 4.92 ± 0.40 mm, and 2.90 ± 0.20 mm. The distances between pineal gland and superior colliculus as well as splenium of corpus callosum were 3.96 ± 0.92 mm and 4.3 ± 1.89 mm, respectively. The PGV was 54.1 ± 7.02 mm. Significant sex differences were found in pineal gland length (P < 0.001), cranial cavity diameter (P < 0.001), pineal gland index (P < 0.001) and PGV values (P = 0.02). The prevalence of cystic pineal gland was 36.4% in total subjects, 41.7% in males and 32.4% in females. No linear relationship was found between age and pineal gland parameters. We measured the pineal gland morphology based on MRI images. Significant influences on pineal gland parameters were found in subjects with different sex, whereas no effect was observed from age.

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology.

Location, Isolation, and Identification of Mesenchymal Stem Cells from Adult Human Sweat Glands.

Sweat glands (SGs) are spread over almost the entire surface of the human body and are essential for thermoregulation. Theoretically, tissue-specific stem cells (TSSCs) are excellent candidate cells for the regeneration of SGs due to their genetic stability and differentiation ability. Herein, we attempted to isolate TSSCs derived from adult human sweat glands (ahSGs). ahSGs were localized and identified by H&E staining, double immunofluorescence staining, transmission electron microscope (TEM), and immuno-TEM. We found a population of cells with stem cell characteristics (SGSCs), located in basal myoepithelial cells of the secretory portion of the solenoid bulb. The SGSCs expressed alpha-smooth muscle actin (α-SMA) and showed the typical characteristics of mesenchymal stem cells (MSCs), with a positive antigen profile for CD44, CD73, CD90, and CD105, and had the multilineage differentiation potential to osteoblasts and adipocytes. In addition, the isolated α-SMA positive cells remained stably phenotypic and proliferative cycles at passage 12. This is the first report of successful isolation of MSC-like cells from ahSGs, which may contribute to wound repair and SG regeneration.

C/EBPβ LIP and c-Jun synergize to regulate expression of the murine progesterone receptor.

CCAAT/enhancer binding protein β (C/EBPβ) is required for murine mammary ductal morphogenesis and alveologenesis. Progesterone is critical for proliferation and alveologenesis in adult mammary glands, and there is a similar requirement for progesterone receptor isoform B (PRB) in alveologenesis. We examined C/EBPβ regulation of PR expression. All three C/EBPβ isoforms, including typically inhibitory LIP, transactivated the PR promoter. LIP, particularly, strongly synergized with c-Jun to drive PR transcription. Endogenous C/EBPβ and c-Jun stimulated a PR promoter-reporter and these two factors showed promoter occupancy on the endogenous PR gene. Additionally, LIP overexpression elevated endogenous PR protein expression. In pregnancy, both PRB and the relative abundance of LIP among C/EBPβ isoforms increase. Consistent with a role in PRB expression, in vivo C/EBPβ and PR isoform A expression showed mutually exclusive localization in mammary epithelium, while C/EBPβ and PRB largely co-localized. We suggest a critical role for C/EBPβ, particularly LIP, in PRB expression.

Basal-like Breast Cancers: From Pathology to Biology and Back Again.

Human breast cancers referred to as “basal-like” are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients' samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. However, both also have limitations. Here, we review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation.

The role of epithelial growth factors and insulin growth factors in the adrenal neoplasms.

Human fetal and adult adrenal gland express both insulin growth factor-1 (IGF-1) and IGF-2, their receptors (IGF-Rs) and a variety of specific IGF binding proteins suggesting their potential role in the regulation of adrenal growth and function. IGF-2 overexpression is essential for the growth of monoclonal lesions, such as large benign adenomas (ACA) and adrenocortical carcinomas (ACC) and has been found to contribute to tumorigenesis in Beckwith-Wiedemann syndrome. IGF-2 is the most highly expressed gene observed in more than 85% of ACCs. However, no significant differences in clinical, biological and transcriptomic traits were found between tumors with high and low expression of IGF-2. On the contrary, the expression of IGF-1R, mediating the IGF-2 effects in vivo, was more discriminant between malignant (overexpression) and benign tumors. Data on the role of epithelial growth factor (EGF) and its receptor (EGF-R) in adrenocortical tumorigenesis are controversial. Several studies have shown EGF-R overexpression in ACCs but not in benign ACAs, suggesting that EGF-R could potentially be used as a marker for the differential diagnosis of ACAs and ACCs. Although, in vitro and animal studies provide promising results in the therapeutic role of IGF and EGF pathway inhibitors, the available data in humans are still not encouraging. Herein, we aim to present recent data on the role of IGF and EGF pathways in adrenal development and tumorigenesis and their potential implication in the treatment of the ACC, a rare malignancy with very poor prognosis.

Histopathological and morphological alterations in salivary gland of House fly induced by oral administration Thiamethoxam.

The current work the effect of Actara insecticide belongs to chemical family Neonicotinoid. The active component of thiamethoxam in three concentrations: 0.750 ppm, 1.5 ppm and 2.25ppm on adult house fly salivary glands. Histopathological and morphological effects revealed important alterations produced by this insecticide in histological and morphology of the adult house fly gland tissue categorized by increasing gland duct lumen diameter. These alterations are possibly related with excretion function of salivary gland might be accountable for removing this insecticide. Results show thiamethoxam is a powerful insecticide that performances histologically in salivary glant tissue, triggering alterations in the glands form, cytoplasm with extreme vacuolation ,disruption cell membrane, obvious disorganization tissues cells, terminating in progressive deteriorating phase with changes in nucleus glandular cell's, such alterations occurred together in its size and form of gland, disintegration of nucleus, and presence of apoptosis(fragmentation) nucleus, accelerating the process of glandular degeneration ,and interfering with feeding process of house fly particularly when the peak concentration of insecticide was used.

Serrate/Notch Signaling Regulates the Size of the Progenitor Cell Pool in Drosophila Imaginal Rings.

Drosophila imaginal rings are larval tissues composed of progenitor cells that are essential for the formation of adult foreguts, hindguts, and salivary glands. Specified from subsets of ectoderm in the embryo, imaginal ring cells are kept quiescent until midsecond larval instar, and undergo rapid proliferation during the third instar to attain adequate numbers of cells that will replace apoptotic larval tissues for adult organ formation. Here, we show that Notch signaling is activated in all three imaginal rings from middle embryonic stage to early pupal stage, and that Notch signaling positively controls cell proliferation in all three imaginal rings during the third larval instar. Our mutant clonal analysis, knockdown, and gain-of-function studies indicate that canonical Notch pathway components are involved in regulating the proliferation of these progenitor cells. Both trans-activation and cis-inhibition between the ligand and receptor control Notch activation in the imaginal ring. Serrate (Ser) is the ligand provided from neighboring imaginal ring cells that trans-activates Notch signaling, whereas both Ser and Delta (Dl) could cis-inhibit Notch activity when the ligand and the receptor are in the same cell. In addition, we show that Notch signaling expressed in middle embryonic and first larval stages is required for the initial size of imaginal rings. Taken together, these findings indicate that imaginal rings are excellent in vivo models to decipher how progenitor cell number and proliferation are developmentally regulated, and that Notch signaling in these imaginal tissues is the primary growth-promoting signal that controls the size of the progenitor cell pool.

Adjuvant therapy in major salivary gland cancers: Analysis of 8580 patients in the National Cancer Database.

Evidence surrounding the effect of adjuvant treatment in salivary gland cancers is limited. The benefit of adding chemotherapy to adjuvant treatment is also of interest. We investigated the association of these treatments with survival and whether this differed by stage or the presence of adverse features. A retrospective study of adult salivary gland cancer cases diagnosed from 2004 to 2013 in the National Cancer Data Base (NCDB) was conducted. Treatment with adjuvant radiotherapy was associated with improved survival for both patients with early-stage (hazard ratio [HR] 0.744; P = .004) and late-stage (HR 0.688; P < .001) disease with adverse features. Further addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features was not associated with a survival benefit (HR 1.028; P = .705). Adjuvant radiotherapy is associated with improved survival for patients with adverse features, regardless of stage. The addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features is not associated with improved outcomes.

Effect of Diet on Adult House Fly (Diptera: Muscidae) Injected With the Salivary Gland Hypertrophy Virus (MdSGHV).

Research to date on the salivary gland hypertrophy virus (SGHV) in three species of flies has focused on adult flies having access to and taking a proteinaceous diet. Since many studies have shown that diet affects viral infection in numerous organisms, this study examined the effect of a protein-free diet on the effect of the SGHV virus in adult house flies, Musca domestica. L. Adults infected with the virus, and maintained on a sugar diet only, showed salivary glands with a blue rather than a grayish color and mild hypertrophy compared with protein-fed flies. It was possible to retrieve the virus from these glands and successfully infect noninfected flies. When injected at various ages, female flies fed only sugar showed that regardless of age, sugar-fed flies still became infected and showed the pathology of the glands. In addition, electron microscope studies revealed at the ultrastructural level that there was no difference between viral replication in cells from salivary glands of adults fed a proteinaceous-free diet and those feeding on protein.

Does the Mouse Mammary Gland Arise from Unipotent or Multipotent Mammary Stem/Progenitor Cells?

The presence of long-lived lineage restricted progenitor and multipotent progenitor cells in adult mouse mammary gland for cancer development is compelling. Mammary cancers are phenotypically diverse This might be explained by transformation of long-lived, lineage-limited progenitor subpopulations. Mammary multipotent epithelial stem cells and their environmental niches must be considered, since their niche(s), once empty might be occupied by lineage-limited progenitors that are proximal. The existence of premalignant mammary populationst that manifest characteristics of lineage limitation argues strongly for this proposition.

CD24 and CD49f expressions of E14.5 mouse mammary anlagen cells define putative distribution of earlier embryonic mammary stem cell activities.

Stem cell biology offers promise for understanding the origins of the mammary gland. However, the distribution of mammary stem cell (MaSC) activities at earlier embryonic stages has not been fully identified. The markers for sorting adult MaSC, CD24, CD29, and CD49f have been applied to analyze fetal MaSCs. Here we explored mammary anlagen MaSCs by investigating the expression of CD24 and CD49f. According to the comparative analysis between adult mammary gland and fetal mammary anlagen, we found that fetal mouse mammary anlagen may possess a high percentage of potential MaSCs. Flow cytometry analysis revealed 2 distinct mammary anlagen populations: Lin-CD24med and Lin-CD24high. Sphere-forming and mammary repopulating assays confirmed that the stem cell activity of E14.5 mouse mammary anlagen was restricted to the Lin-CD24med cell population. Furthermore, CD24med mammary anlagen cells were separated into Lin-CD24medCD49f+ and Lin-CD24medCD49f- populations and identified, respectively. The results proved that the mammary anlagen Lin-CD24medCD49f+ cell population possesses more stem cell activities than the Lin-CD24medCD49f- cell population. However, a limited numbers of stem cells and large numbers of stromal cells were identified in mammary anlagen in the Lin-CD24med cell population.

CD29 is highly expressed on epithelial, myoepithelial, and mesenchymal stromal cells of human salivary glands.

The phenotype of the cells present in the ductal region of salivary glands has been well characterized. However, it is imperative to identify novel biomarkers that can identify different cell types present in other glandular components for the development of therapeutic strategies and diagnostics of salivary gland disorders and malignancies. Our study aimed at the characterization of the expression and distribution of various cell surface markers, especially with a focus on CD29 in human fetal as well as adult glands. Paired human midgestation fetal and adult parotid, sublingual, and submandibular glands were collected. Phenotypic expression of various lineage-specific cell surface markers including CD29 was investigated in freshly collected glands. The findings were further corroborated by immunohistochemistry. Enriched expression of CD29 was found on acinar and ductal epithelial, mesenchymal stromal, and myoepithelial cells; CD29+ cells co-expressed epithelial (CD324, CD326, NKCC1, and CD44), mesenchymal (CD73, CD90, vimentin, and CD34), and myoepithelial (α-SMA) cell-specific progenitor markers in both fetal as well as adult salivary glands. CD29 is widely expressed in human salivary glands, and it could serve as a potential biomarker for devising novel cellular therapeutic and diagnostic strategies for salivary gland disorders and malignancies.

ЛИМФОМЫ СРЕДОСТЕНИЯ: ПОСТПРОЦЕССИНГОВАЯ ОБРАБОТКА ТОМОГРАФИЧЕСКИХ ИЗОБРАЖЕНИЙ

The syndrome of lymphadenopathy (lymph-node hyperplasia) takes place in many diseases that are different by etiology, clinical course, methods of treatment and prediction. While identifying the cause of lymphadenopathy the diagnostic search should be based on the clinical situation (the character of lymphadenopathy, the presence of other symptoms, anamnestic data, the character of changes in the peripheral blood and others). The choice of the most informative method of diagnosis is defined by the diagnostic hypothesis with the consideration of the data of the primary examination of the patient, the parameters of the peripheral blood as well as the values of sensitivity and specificity of the corresponding method of study for verification of the disease supposed. The basis of this research was the material of computed-tomography examination of chest organs in 491 patients with different forms of mediastinum lymphomas in the consultative policlinic of the Far-Eastern Scientific Center of Physiology and Pathology of Respiration from 2011 till 2017. Among them there were sarcoidosis of intrathoracic lymph glands of the first, second and partially third stage (n=432); Hodgkin's lymphoma (n=17); metastases in lymph glands of mediastinum (n=25); lymphosarcoma (n=12), tuberculosis of lymph glands in adults (n=5). Beside prevailing digital radiologic studies, multispiral computed tomography was done to all of them and 78% went through fiberbronchoscopy. The verification was in 82% of patients: transbronchial biopsy under ultrasound visualization (72%) and transthoracic open biopsy (28%).

Neurturin Gene Therapy Protects Parasympathetic Function to Prevent Irradiation-Induced Murine Salivary Gland Hypofunction

Head and neck cancer patients treated with irradiation often present irreversible salivary gland hypofunction for which no conventional treatment exists. We recently showed that recombinant neurturin, a neurotrophic factor, improves epithelial regeneration of mouse salivary glands in ex vivo culture after irradiation by reducing apoptosis of parasympathetic neurons. Parasympathetic innervation is essential to maintain progenitor cells during gland development and for regeneration of adult glands. Here, we investigated whether a neurturin-expressing adenovirus could be used for gene therapy in vivo to protect parasympathetic neurons and prevent gland hypofunction after irradiation. First, ex vivo fetal salivary gland culture was used to compare the neurturin adenovirus with recombinant neurturin, showing they both improve growth after irradiation by reducing neuronal apoptosis and increasing innervation. Then, the neurturin adenovirus was delivered to mouse salivary glands in vivo, 24 hr before irradiation, and compared with a control adenovirus. The control-treated glands have ∼50% reduction in salivary flow 60 days post-irradiation, whereas neurturin-treated glands have similar flow to nonirradiated glands. Further, markers of parasympathetic function, including vesicular acetylcholine transporter, decreased with irradiation, but not with neurturin treatment. Our findings suggest that in vivo neurturin gene therapy prior to irradiation protects parasympathetic function and prevents irradiation-induced hypofunction.

Functional characterization and genomic studies of a novel murine submandibular gland epithelial cell line.

A better understanding of the normal and diseased biology of salivary glands (SG) has been hampered, in part, due to difficulties in cultivating and maintaining salivary epithelial cells. Towards this end, we have generated a mouse salivary gland epithelial cell (mSGc) culture system that is well-suited for the molecular characterization of SG cells and their differentiation program. We demonstrate that mSGc can be maintained for multiple passages without a loss of proliferation potential, readily form 3D-spheroids and importantly express a panel of well-established salivary gland epithelial cell markers. Moreover, mSGc 3D-spheroids also exhibit functional maturation as evident by robust agonist-induced intracellular calcium signaling. Finally, transcriptomic characterization of mSGc by RNA-seq and hierarchical clustering analysis with adult organ RNA-seq datasets reveal that mSGc retain most of the molecular attributes of adult mouse salivary gland. This well-characterized mouse salivary gland cell line will fill a critical void in the field by offering a valuable resource to examine various mechanistic aspects of mouse salivary gland biology.