Gland Epithelium Research Articles

Efficient Surface Immobilization of Chemically Modified Hyaluronans for Enhanced Bioactivity and Survival of In Vitro-Cultured Embryonic Salivary Gland Mesenchymal Cells.

Embryonic salivary gland mesenchyme (eSGM) secretes various growth factors (bioactives) that support the proper growth and differentiation of salivary gland epithelium. Therefore, eSGM cells can be used as feeder cells for in vitro-cultured artificial salivary gland if their survival and bioactivity are properly maintained. As eSGM is encapsulated in a hyaluronan (HA)-rich developmental milieu, we hypothesized that mimicking this environment in vitro via surface immobilization of HA might enhance survival and bioactivity of eSGM. In this study, various HA derivatives, conjugated with catechol (HA–CA), thiol (HA–SH), or amine (HA–EDA) moieties, respectively, were screened for their efficacy of culturing eSGM-derived feeder cells in vitro. Among these HA derivatives, HA–CA showed the highest surface coating efficiency and growth enhancement effect on the embryonic submandibular gland. In addition, the HA–CA coating enhanced the production of growth factors EGF and FGF7, but not FGF10. These effects were maintained when eSGM cells isolated from the embryonic salivary gland were re-seeded to develop the feeder layer cells. CD44s (a major HA receptor) in eSGM cells were clustered at the cell membrane, and enhanced EGF expression was detected only in CD44 cluster-positive cells, suggesting that membrane clustering of CD44 is the key mechanism for the increased expression of EGF.

Do uterine PTGS2, PGFS, and PTGFR expression play a role in canine uterine inertia?

The aetiology of primary uterine inertia (PUI), which is the most common cause of canine dystocia, is still not elucidated. Prostaglandins (PGs) play a crucial role in parturition. We hypothesized that the expression of prostaglandin endoperoxidase synthase 2 (PTGS2), PGF2α synthase (PGFS), and corresponding receptor (PTGFR) is altered in PUI. We investigated PTGS2, PGFS, and PTGFR mRNA expression, and PTGS2 and PGFS protein expression in interplacental (IP) and uteroplacental sites (UP) in bitches with PUI, obstructive dystocia (OD), and prepartum (PC). PTGS2, PGFS, and PTGFR mRNA expression did not differ significantly between PUI and OD (IP/UP). PTGFR ratio in UP was higher in PC than in OD (p = 0.014). PTGS2 immunopositivity was noted in foetal trophoblasts, luminal and superficial glandular epithelial cells, smooth muscle cells of both myometrial layers, and weakly and sporadically in deep uterine glands. PGFS was localized in luminal epithelial cells and in the epithelium of superficial uterine glands. PTGS2 and PGFS staining was similar between PUI and OD, while PGFS protein expression differed between OD and PC (p = 0.0215). For PTGS2, the longitudinal myometrial layer of IP stained significantly stronger than the circular layer, independent of groups. These results do not support a role for PTGS2, PGFS, and PTGFR in PUI. Reduced PGFS expression in IP during parturition compared with PC and the overall lack of placental PGFS expression confirm that PGFS is not the main source of prepartal PGF2alpha increase. The difference in PTGS2 expression between IP myometrial layers warrants further investigation into its physiological relevance.

Comparative study on lesions of reproductive disorders of cows and female dromedary camels slaughtered at Addis Ababa, Adama and Akaki abattoirs with bacterial isolation and characterization

BackgroundReproduction is a basic prerequisite to efficient livestock production. Reproductive performance depends on the normal structure and function of genital organs. A cross-sectional study was conducted from November 2016 to May 2017 to identify and compare the frequency of reproductive tract pathological lesions and to isolate bacteria associated to uterine lesions in female dromedary camels and cows slaughtered at Akaki camel slaughterhouse and Addis Ababa and Adama municipal abattoirs. Purposive sampling technique was employed to include and examine the reproductive tracts of all slaughtered animals (280; 140 cows and 140 camels) during the study period.ResultThe study examined a total of 280 (140 cows and 140 camels) reproductive tracts. Various pathological lesions with different degrees of severity were observed in 48 (34.2%) and 51 (36.4%) of dromedary camels and cows, respectively. In dromedary camels, the most prevalent lesion was uterine lesions (21.4%) followed by ovarian lesions (7.14%); while in cows, ovarian lesions were the most prevalent (16.4%) followed by uterine lesions (14.2%). In general, 56 bacteria were isolated from cows’ uterine lesion, the Staphylococcus species (28.5%), Streptococci species (19.6%), Coynebacterium species (8.9%), Escherichia coli (26.78%), Salmonella species (10.7%) and Klebsiella species (5.35%) being the most representative isolates. In camels, however, 45 bacteria were isolated from uterine lesions with higher prevalence of Escherichia coli (35.5%), Staphylococcus species (26.6%), Streptococcus species (13.3%), Pseudomonas species (6.6%), Proteus species (4.4%), Salmonella species (8.8%) and Klebsiella species (4.4%). Bacteriological data showed that the major isolates were similar, although slightly more frequent in occurrence in cows. Microscopically, uterine inflammatory lesions evidenced endometrial glands degeneration, epithelium sloughing, peri-glandular cuffing, and inflammatory cells infiltration.ConclusionsIn female dromedary camels and cows, pathological lesions of the reproductive tract showed great prevalence, with similarity in bacterial isolates in both species. The role of each reproductive lesion and bacterial isolates as causal agents of reproductive failures in these livestock species, however, needs further investigation.

The basitarsal sulcus gland, a novel exocrine structure in ants

The basitarsus of the mid- and/or hindlegs of several Amblyoponinae ants shows a deep longitudinal groove or sulcus on its anterior face in workers and queens. Histological examination reveals this sulcus is associated with a conspicuous novel epithelial gland, which brings the number of exocrine glands in the legs of ants to 25. The ultrastructural characteristics of the gland show the presence of a well-developed smooth endoplasmic reticulum. This is indicative for the elaboration of a non-proteinaceous and thus possibly pheromonal secretion. Behavioural observations show that this secretion is collected by the tarsomeres and spread onto the brood and nest, suggesting a role in nestmate recognition. A similar basitarsal sulcus gland was also found in Nothomyrmecia, Paraponera and Tetraponera, which represents both a wide phylogenetic and ecological distribution, as it includes arboreal, ground-dwelling as well as subterranean taxa.

Genetics of CFTR and male infertility.

Cystic fibrosis (CF) is a rare autosomal-recessive disorder manifested as multisystem organ dysfunction. The cystic fibrosis transmembrane conductance regulator (CFTR) protein functions as an ion transporter on the epithelium of exocrine glands, regulating secretion viscosity. The CFTR gene, encoded on chromosome 7, is required for the production and trafficking of the intact and functional CFTR protein. Literally thousands of human CFTR allelic mutations have been identified, each with varying impact on protein quality and quantity. As a result, individuals harboring CFTR mutations present with a spectrum of symptoms ranging from CF to normal phenotypes. Those with loss of function but without full CF may present with CFTR-related disorders (CFTR-RDs) including male infertility, sinusitis, pancreatitis, atypical asthma and bronchitis. Studies have demonstrated associations between higher rates of CFTR mutations and oligospermia, epididymal obstruction, congenital bilateral absence of the vas deferens (CBAVD), and idiopathic ejaculatory duct obstruction (EDO). Genetic variants are detected in over three-quarters of men with CBAVD, the reproductive abnormality most classically associated with CFTR aberrations. Likewise, nearly all men with clinical CF will have CBAVD. Current guidelines from multiple groups recommend CFTR screening in all men with clinical CF or CBAVD though a consensus on the minimum number of variants for which to test is lacking. CFTR testing is not recommended as routine screening for men with other categories of infertility. While available CFTR panels include 30 to 96 of the most common variants, complete gene sequencing should be considered if there is a high index of suspicion in a high-risk couple (e.g., partner is CFTR mutation carrier). CF treatments to date have largely targeted end-organ complications. Novel CFTR-modulator treatments aim to directly target CFTR protein dysfunction, effectively circumventing downstream complications, and possibly preventing symptoms like vasal atresia at a young age. Future gene therapies may also hold promise in preventing or reversing genetic changes that lead to CF and CFTR-RD.

Abstract PS17-32: Characterization of HOXB13-induced estrogen receptor reprogramming in breast cancer cells

Abstract Background: The Breast Cancer Index (BCI) is a gene expression-based signature that consists of two functional biomarker panels, HOXB13/IL17BR (H/I) and Molecular Grade Index (MGI), that interrogate important proliferation and estrogen signaling pathways in breast cancer. The BCI prognostic score reports individualized risk of overall and late distant recurrence and is based on the algorithmic combination of the H/I ratio and MGI, while the predictive component, BCI (H/I), reports a categorical prediction of high versus low likelihood of benefit from extended endocrine therapy.The homeobox transcription factor HOXB13 has previously been shown to reprogram genome-wide binding of the androgen receptor (AR) during prostate cancer tumorigenesis, where it colocalizes with FOXA1 at reprogrammed AR binding sites. The aim of the current study was to characterize the potential role of HOXB13 in estrogen receptor (ER) reprogramming by analyzing changes in the global ER binding pattern induced by transient overexpression of HOXB13 in breast cancer cells. In addition, gene ontology (GO) analysis was performed to delineate the functional role of HOXB13 in modulating estrogen signaling and response to endocrine therapy.Methods: HOXB13 was overexpressed in MCF-7 cells by electroporating HOXB13 mRNA, or eGFP mRNA as control. Cells were harvested at different time points and analyzed by western blot and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) using antibodies against ER, HOXB13, FOXA1 and H3K27ac. After aligning reads with Bowtie2, peak calling and data integration were performed using HOMER v4.10. Gene ontology (GO) analysis was performed using the Genomic Regions Enrichment of Annotations Tool (GREAT v4.0.4) (http://great.stanford.edu/) to identify annotations enriched among genes near ER genomic binding sites.Results: ChIP-seq analysis revealed substantial binding of HOXB13 to a large number of genomic binding sites compared to the eGFP control. HOXB13 overexpression in ER+ breast cancer cells significantly increased ER binding with a majority of ER binding sites being co-bound by FOXA1 and HOXB13. GO analysis of both proximal and distal genomic regions showed significant enrichment of genes associated with mammary gland development, such as “mammary gland epithelium development”, “mammary gland development”, and “mammary gland epithelial cell differentiation”.Conclusion: Findings from this analysis show that transient HOXB13 overexpression reprograms and expands the ER binding pattern in breast cancer cells. Genomic regions newly bound by ER are enriched for genes involved in mammary gland and epithelial differentiation suggesting that HOXB13 activates ER transcriptional programs that link oncogenic and developmental pathways. These results will be compared to ongoing experiments using an inducible HOXB13 expression system to assess the effects of HOXB13 expression on ER binding and function in response to estradiol and tamoxifen. Citation Format: Kai Treuner, Dominic Schenone, Christopher Benner, Catherine A Schnabel, Sven Heinz. Characterization of HOXB13-induced estrogen receptor reprogramming in breast cancer cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-32.

Niacin stimulates EPH4EV mammary epithelial cell proliferation and mammary gland development in pubertal mice through activation of AKT/mTOR and ERK1/2 signaling pathways.

Previous studies have shown the effects of vitamins on the development of the mammary gland. However, the role of niacin in this process has not been reported. Therefore, the aim of this study is to investigate the effects of niacin on mammary gland development in pubertal mice and to use a mouse mammary epithelial cell line to study the underlying mechanism. The results showed that niacin could activate the AKT/mTOR and ERK signaling pathways and increase phosphorylation of 4EBP1 to promote the synthesis of cell proliferation markers, leading to the dissociation of the Rb-E2F1 complex in mMECs. In addition, 0.5% niacin promoted mammary duct development, increased the expression of cyclin D1/D3 and PCNA and activated Akt/mTOR and ERK1/2 in the mammary glands of pubertal mice. These results strongly suggest that niacin stimulates mammary gland development in pubertal mice through the Akt/mTOR and ERK1/2 signaling pathways.

Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis.

C-reactive protein (CRP) is a commonly used serum biomarker for detecting sepsis in neonates. After the onset of sepsis, serial measurements are necessary to monitor disease progression; therefore, a non-invasive detection method is beneficial for neonatal well-being. While some studies have shown a correlation between serum and salivary CRP levels in septic neonates, the causal link behind this correlation remains unclear. To investigate this relationship, CRP was examined in serum and saliva samples from 18 septic neonates and compared with saliva samples from 22 healthy neonates. While the measured blood and saliva concentrations of the septic neonates varied individually, a correlation of CRP levels between serum and saliva samples was observed over time. To clarify the presence of active transport of CRP across the blood–salivary barrier (BSB), transport studies were performed with CRP using in vitro models of oral mucosa and submandibular salivary gland epithelium. The results showed enhanced transport toward saliva in both models, supporting the clinical relevance for salivary CRP as a biomarker. Furthermore, CRP regulated the expression of the receptor for advanced glycation end products (RAGE) and the addition of soluble RAGE during the transport studies indicated a RAGE-dependent transport process for CRP from blood to saliva.

Masses of the Lacrimal Gland: Evaluation and Treatment.

Lacrimal gland lesions account for approximately 9 to 10% of all biopsied orbital masses. Potential causes include nongranulomatous and granulomatous inflammation, autoimmune disease, lymphoproliferative disorders, benign epithelial proliferation, malignant neoplasia, and metastatic disease. Inflammatory lesions and lymphoproliferative disorders are the most common and may be unilateral or bilateral; they may also be localized to the orbit or associated with systemic disease. Both benign and malignant epithelial lacrimal gland masses tend to be unilateral and involve the orbital lobe, but a more rapid onset of symptoms and periorbital pain strongly suggest malignant disease. On orbital imaging, both inflammatory and lymphoproliferative lesions conform to the globe and surrounding structures, without changes in adjacent bone, whereas epithelial lacrimal gland masses often show scalloping of the lacrimal gland fossa. Malignant epithelial lacrimal gland tumors can also have radiographic evidence of bony invasion and destruction. Masses of the lacrimal gland may be due to a broad range of pathologies, and a good working knowledge of common clinical characteristics and radiographic imaging findings is essential for diagnosis and treatment. All patients with inflammatory, lymphoproliferative, and epithelial neoplastic lesions involving the lacrimal gland require long-term surveillance for disease recurrence and progression.

The Possible Role of Sclerostin in the Pathogenesis of Tympanosclerosis

Objective: The aim of this study was to investigate sclerostin (SOST) expression in a rat model of experimental tympanosclerosis (TS) and its possible role in the formation of TS. Materials and Methods: Thirty-four SD rats were randomly divided into 2 groups: experimental group (n = 17) and normal group (n = 17). The left tympanic cavities in the experimental group were inoculated with methicillin-resistant Staphylococcus aureus. The changes of tympanic membranes were examined and recorded under otoendoscope. Haematoxylin-eosin staining was adopted to detect the morphological changes in the tympanic membrane and middle ear mucosa. Immunohistochemistry and Western blot analysis were used to observe the expression of SOST, Wnt3a, β-catenin, and P-ERK1/2. Results: In the experimental group, sclerotic lesions were observed in 54.5% ears in the end of 6 weeks. Morphological changes such as mucosa incrassation, inflammatory cells infiltration, fibrous tissue proliferation, and interstitial tissue incrassation prominently appeared in the tympanic membrane and middle ear mucosa. SOST protein was mainly distributed in the cytoplasm of epithelial cells and gland cells, the expression of which increased significantly in the calcified experimental ears. In addition, expression levels of Wnt3a, β-catenin, and P-ERK1/2 increased significantly in the calcified group too. Conclusion: The upregulated expression level of SOST may be involved in the formation of TS, first, through the pro-phosphorylation of ERK1/2 in the inflammatory stage, and then through the enhancement of Wnt3a in the osteogenic stage.

Epithelial salivary gland tumors - a monocentric retrospective studyof South Saxony-Anhalt

The purpose of this research was to analyze all epithelial salivary gland tumors in this region in a comprehensive monocentric, retrospective study. In the period from 1993 to 2017, all patients with the diagnosis of epithelial salivary gland tumors either treated at the Department of Oral and Maxillofacial Plastic Surgery of the Martin Luther University, Halle-Wittenberg (MLU), University hospital and/or processed at the Institute of Pathology of the MLU, University hospital and/or registered between 2000 and 2017 by the "Statistisches Landesamt" Sachsen-Anhalt were analyzed. The following parameters were summarized and statistically analyzed in a database using SPSS 21.5: demographic data, tumor localization, entity, therapy and disease course. 382 patients with the diagnosis of epithelial salivary gland neoplasia were identified. With 71 % the most frequent tumor localization was the glandula parotis [n = 271]. 15 % of the tumors originated from minor salivary glands [n = 57]. Most tumors were benign at over 80 % [n = 307]. In Saxony-Anhalt, 5586 patients with epithelial salivary gland tumors were reported in the mentioned period. To the best of our knowledge this is the first epidemiologic analysis of frequency, valency and therapy of salivary gland tumors in Saxony-Anhalt. The results confirm the predominance of benign epithelial salivary gland tumors, most of all pleomorphic adenoma in the glandula parotis. Concerning the group of malignant epithelial salivary gland tumors adenoid cystic carcinoma located in the minor salivary glands were most common.

CXCR4 Regulates Temporal Differentiation via PRC1 Complex in Organogenesis of Epithelial Glands

CXC-chemokine receptor type 4 (CXCR4), a 7-transmembrane receptor family member, displays multifaceted roles, participating in immune cell migration, angiogenesis, and even adipocyte metabolism. However, the activity of such a ubiquitously expressed receptor in epithelial gland organogenesis has not yet been fully explored. To investigate the relationship between CXCL12/CXCR4 signaling and embryonic glandular organogenesis, we used an ex vivo culture system with live imaging and RNA sequencing to elucidate the transcriptome and protein-level signatures of AMD3100, a potent abrogating reagent of the CXCR4-CXCL12 axis, imprinted on the developing organs. Immunostaining results showed that CXCR4 was highly expressed in embryonic submandibular gland, lung, and pancreas, especially at the periphery of end buds containing numerous embryonic stem/progenitor cells. Despite no significant increase in apoptosis, AMD3100-treated epithelial organs showed a retarded growth with significantly slower branching and expansion. Further analyses with submandibular glands revealed that such responses resulted from the AMD3100-induced precocious differentiation of embryonic epithelial cells, losing mitotic activity. RNA sequencing analysis revealed that inhibition of CXCR4 significantly down-regulated polycomb repressive complex (PRC) components, known as regulators of DNA methylation. Treatment with PRC inhibitor recapitulated the AMD3100-induced precocious differentiation. Our results indicate that the epigenetic modulation by the PRC-CXCR12/CXCR4 signaling axis is crucial for the spatiotemporal regulation of proliferation and differentiation of embryonic epithelial cells during embryonic glandular organogenesis.

Sublingual gland neoplasms: clinicopathological study of 8 cases.

Background Sublingual gland neoplasms are very rare and the majority of them are malignant. The aim of this study was to evaluate the clinical course, treatment, and outcomes of these uncommon neoplasms based on the authors’ experience and the recent literature.Material and Methods The medical charts of 8 patients with primary epithelial sublingual gland tumors treated between 1994 and 2020 were reviewed.Results Malignant tumors comprised 75% (6/8) of cases. Adenoid cystic carcinoma was the most common (50%, 3/6) and characterized by high risk of local recurrence and lung metastasis. Pleomorphic adenoma was the only representative of benign tumors with no evidence of local recurrence in follow up.Conclusions Treatment of choice of sublingual gland tumors is surgery. However, due to the fact that adenoid cystic carcinoma is the most common malignancy with poor prognosis, surgical treatment should be combined with postoperative radiotherapy. Benign sublingual tumors are less common and treatment of choice in these cases is tumor resection together with sublingual gland. Key words:Salivary gland neoplasms, sublingual gland, pleomorphic adenoma, adenoid cystic carcinoma, mucoepidermoid carcinoma.

LncRNA GAS5 inhibits Invasion and Migration of Lung Cancer through influencing EMT process.

Background: Lung cancer is a malignant tumor in mammary gland epithelium with high morbidity and mortality among women worldwide. Long noncoding RNA GAS5 (GAS5) has been proved to be closely related with tumor progression. However, the influence of GAS5 on lung cancer and the specific mechanism remain unclear.Methods: Cell invasion, cell migration, cell apoptosis and cell cycle were investigated after transfection with pcDNA-GAS5 and sh-GAS5. Sizes of tumors were measured by establishing transplanted tumor model in vivo. E-cadherin and N-cadherin expressions were investigated.Results: Cell invasion and migration were inhibited markedly in GAS5 overexpressed cell line. Cell cycle results indicated that the percentage of S-phase cells was increased, and G2-phase was reduced in the GAS5 overexpression cell line. Tumor size was suppressed obviously after GAS5 overexpression treatment. GAS5 markedly inhibited the expression of E-cadherin and induced the expression of N-cadherin. GAS5 overexpression significantly inhibited lung cancer cell proliferation by increasing the E-cadherin and decreasing N-cadherin.Conclusions: These findings provide novel evidence that GAS5 can be viewed as an anti-lung cancer agent through affecting EMT pathway.

Histology, lectin histochemistry and ultrastructure of interdigital gland in crossbred sheep

Abstract: Histology, lectin histochemistry and ultrastructure of interdigital gland in sheep was studied using six adult cross bred sheep of either sex collected from the Meat Technology Unit, College of Veterinary and Animal Sciences, Mannuthy. The manus and pes were detached from the rest of limbs and after recording the gross observations, the interdigital glands were fixed in 10 per cent neutral buffered formalin and processed for histological examinations. Stratified squamous epithelium with a prominent keratin layer lined the lumen, similar to the skin over the dorsal surface of manus and pes. The epidermis presented mucosal folds, which projected into the lumen. The dermis contained small sebaceous glands, hair follicles of different sizes, arrector pili muscles and apocrine sweat glands. The secretory epithelium of sweat glands was lined with a simple layer of cuboidal and relatively flattened cells. The excretory ducts of these glands were lined by cuboidal cells, with darker appearance than its secretory portion. The fibrous capsule was composed of dense connective tissue with collagen, adipose cells, blood vessels and nerve fibers. Glandular secretion and the granules in the stratum granolosum of the surface squamous epithelium showed positive reaction for lectin Ulex europaeus (UEA-I). The apocrine nature of sweat glands was revealed in the ultrastructural studies by scanning electron microscope. Keywords: Interdigital gland, sheep, histology, lectin histochemistry and ultrastructure

Experimental Lagos bat virus infection in straw-colored fruit bats: A suitable model for bat rabies in a natural reservoir species.

Rabies is a fatal neurologic disease caused by lyssavirus infection. Bats are important natural reservoir hosts of various lyssaviruses that can be transmitted to people. The epidemiology and pathogenesis of rabies in bats are poorly understood, making it difficult to prevent zoonotic transmission. To further our understanding of lyssavirus pathogenesis in a natural bat host, an experimental model using straw-colored fruit bats (Eidolon helvum) and Lagos bat virus, an endemic lyssavirus in this species, was developed. To determine the lowest viral dose resulting in 100% productive infection, bats in five groups (four bats per group) were inoculated intramuscularly with one of five doses, ranging from 100.1 to 104.1 median tissue culture infectious dose (TCID50). More bats died due to the development of rabies after the middle dose (102.1 TCID50, 4/4 bats) than after lower (101.1, 2/4; 101.1, 2/4) or higher (103.1, 2/4; 104.1, 2/4) doses of virus. In the two highest dose groups, 4/8 bats developed rabies. Of those bats that remained healthy 3/4 bats seroconverted, suggesting that high antigen loads can trigger a strong immune response that abrogates a productive infection. In contrast, in the two lowest dose groups, 3/8 bats developed rabies, 1/8 remained healthy and seroconverted and 4/8 bats remained healthy and did not seroconvert, suggesting these doses are too low to reliably induce infection. The main lesion in all clinically affected bats was meningoencephalitis associated with lyssavirus-positive neurons. Lyssavirus antigen was detected in tongue epithelium (5/11 infected bats) rather than in salivary gland epithelium (0/11), suggesting viral excretion via the tongue. Thus, intramuscular inoculation of 102.1 TCID50 of Lagos bat virus into straw-colored fruit bats is a suitable model for lyssavirus associated bat rabies in a natural reservoir host, and can help with the investigation of lyssavirus infection dynamics in bats.

An atypical presentation of swelling in the floor of the mouth – A case report

Adenoid cystic carcinoma (ACC) is a neoplasm arising from salivary gland epithelium that affects commonly minor salivary glands, among which palate being the most common site. ACC accounts for about 1% of malignancies that do affect the head and neck region. It usually affects the individuals in the 5th and 6th decade of life. Clinical course is characterized by indolent, locally invasive growth with high propensity for perineural invasion, local recurrence and distant metastasis. Here we report a case with the unusual presentation of ACC in the young male patient. Keywords: Swelling, Floor of the mouth, Salivary gland, Adenoid cystic carcinoma.

Mex3c mutation affects lactation through impairing milk ejection in female mice.

Mouse Mex3c encodes RNA-binding proteins of variant length through alternative splicing. Its mutation results in multiple defects including growth retardation, perturbed energy balance, and defective antiviral innate immunity. Here we report that Mex3c mutation affects mammary gland development and lactation in female mice. Pups of Mex3c mutant dams die of starvation soon after birth. Milk contents are present in the alveoli but deficient in the ducts of the mammary glands in mutant mice. Mutant mice do not show prolactin or oxytocin deficiency. They also develop myoepithelial cells in the mammary glands. Mex3c is expressed in the mammary gland epithelium. Our data suggest that functional defects in mammary gland epithelium or myoepithelial cells could cause lactation defects.

The Effect of Pre-milking Stimulation on Teat Morphological Parameters and Milk Traits in the Italian Water Buffalo.

Water buffaloes (Bubalus bubalis) are very sensitive to environmental stimulus before and during milking, and this explains why disrupted milk ejections due to blood oxytocin level instability are frequent in this species. According to the literature, the manual stimulation (MS) of teats before milking promotes oxytocin release and allows milk ejection to start within 2–3 min. However, the pre-milking stimulation of teats is not always part of the milking routine in Italian buffalo farms; moreover, buffaloes with unstable milk let-down are sometimes treated with exogenous oxytocin (OX). Different types of pre-milking stimulation can impact differently on the mammary gland epithelium and structures and, therefore, on milk yield. In this study, we observed the changes in teat morphological traits before and after the application of three types of stimuli, i.e., no manual stimulation (NS), MS, and OX, in buffaloes reared in an Italian dairy farm. In particular, measurements were available for 23 and 21 buffaloes for front and rear teats, respectively. Subsequently, the effect of the pre-milking stimulation type was estimated on teat morphological characteristics and on milk traits recorded after the application of stimuli. The results showed that the teat canal length was shorter (P < 0.05) after stimulation in the case of MS and OX compared to NS. Cistern diameter was overall greater for MS and lower for OX. On the contrary, teat wall thickness was greater and lower for OX and MS, respectively. Milk yield and quality (fat, protein, and somatic cell score) were similar across the three types of pre-milking stimulation. In perspective, the impact of these types of pre-milking stimulation should be evaluated on a large scale, and the focus might be put on mammary gland epithelium integrity, mastitis incidence, and other udder health indicators in milk, e.g., electrical conductivity, differential somatic cell count, lactose content, and sodium and chloride concentration.

Embryonic lethality and defective mammary gland development of activator-function impaired conditional knock-in Erbb3 V943R mice.

ERBB3 is a pseudokinase domain-containing member of the ERBB family of receptor tyrosine kinases (RTKs). Following ligand binding, ERBB receptors homo- or hetero-dimerize, leading to a head-to-tail arrangement of the intracellular kinase domains, where the "receiver" kinase domain of one ERBB is activated by the "activator" domain of the other ERBB in the dimer. In ERBB3, a conserved valine at codon 943 (V943) in the kinase C-terminal domain has been shown to be important for its function as an "activator" kinase in vitro. Here we report a knock-in mouse model where we have modified the endogenous Erbb3 allele to allow for tissue-specific conditional expression of Erbb3 V943R (Erbb3 CKI-V943R ). Additionally, we generated an Erbb3 D850N (Erbb3 CKI-D850N ) conditional knock-in mouse model where the conserved aspartate in the DFG motif of the pseudokinase domain was mutated to abolish any potential residual kinase activity. While Erbb3 D850N/D850N animals developed normally, homozygous Erbb3 V943R/V943R expression during development resulted in embryonic lethality. Further, tissue specific expression of Erbb3 V943R/V943R in the mammary gland epithelium following its activation using MMTV-Cre resulted in delayed elongation of the ductal network during puberty. Single-cell RNA-seq analysis of Erbb3 V943R/V943R mammary glands showed a reduction in a specific subset of fibrinogen-producing luminal epithelial cells.