Types Of Glandular Cells Research Articles

Tetrodotoxins in Tissues and Cells of Different Body Regions of Ribbon Worms Kulikovia alborostrata and K. manchenkoi from Spokoynaya Bay, Sea of Japan.

Nemerteans, or ribbon worms, possess tetrodotoxin and its analogues (TTXs), neurotoxins of bacterial origin, which they presumably use for capturing prey and self-defense. Most TTXs-containing nemertean species have low levels of these toxins and, therefore, have usually been neglected in studies of TTXs functions and accumulation. In the present study, Kulikovia alborostrata and K. manchenkoi, two closely related species, were analyzed for TTXs distribution in the body using the HPLC-MS/MS and fluorescence microscopy methods. The abundance of TTXs-positive cells was determined in the proboscis, integument, and digestive system epithelium. As a result, six TTXs-positive cell types were identified in each species; however, only four were common. Moreover, the proportions of the toxins in different body parts were estimated. According to the HPLC-MS/MS analysis, the TTXs concentrations in K. alborostrata varied from 0.91 ng/g in the proboscis to 5.52 ng/g in the precerebral region; in K. manchenkoi, the concentrations ranged from 7.47 ng/g in the proboscis to 72.32 ng/g in the posterior body region. The differences observed between the two nemerteans in the distribution of the TTXs were consistent with the differences in the localization of TTXs-positive cells. In addition, TTXs-positive glandular cell types were found in the intestine and characterized for the first time. TTXs in the new cell types were assumed to play a unique physiological role for nemerteans.

Identification of suitable reference genes for RT-qPCR studies in human parathyroid tissue glandular cells

Identifying a proper reference gene allows us to understand fundamental changes in many biological processes. Normalization during gene expression analyses is essential for every tissue/cell type, including parathyroid tissue glandular cells. Quantitative method of gene expression analyses via qRT-PCR method provides the accurate examination of every target gene. There are limited reports to present commonly used reference genes in human parathyroid tissues rather than for glandular cell types. This study aims to determine and compare the most stable to least stable genes for parathyroid tissue cells. 43 human parathyroid tissue obtained from primary and secondary hyperparathyroidism patients and glandular cells isolated enzymatically by the removal of extracellular matrix components. After extraction of the total RNA, cDNA synthesis was performed, then qRT-PCR evaluated 14 candidate reference genes. Stability was determined by RefFinder software (Delta ct, BestKeeper, Genorm, and NormFinder algorithms), and the outcome was evaluated for five groups. Even if assessed with different groups, the most stable genes were RPLP0 and GAPDH, while the CLTC and RNA 18S were the least stable. We have confirmed the comprehensive ranking of the most stable three genes alone with the NormFinder algorithm to understand intergroup variation and found out that RPLP0>GAPDH>PGK1. Lastly, comparisons of relative target gene (GCM2) expression revealed similar expression patterns for the most stable reference genes. The most stable reference gene is recommended for the stages where stability is evaluated using the results of four different approaches using RefFinder. We aspire for this study to assist future research to conduct thorough assessments of appropriate reference genes before engaging in gene expression analyses for parathyroid tissue.

FRI393 Mapping Endometrial Cell-type-specific Disease Signatures A nd Endometrial Organoids In Polycystic Ovary Syndrome

Abstract Disclosure: G. Eriksson: None. C. Li: None. S. Risal: None. H. Pui: None. S. Torstensson: None. A. Linden Hirschberg: None. S. Petropoulos: None. Q. Deng: None. E. Stener-Victorin: None. Women with polycystic ovary syndrome (PCOS) suffer from reduced fertility linked to implantation failure and miscarriage, as well as endometrial cancer, all associated with endometrial dysfunction. We hypothesize that cell-type-specific endometrial dysfunction in insulin-resistant and hyperandrogenic women with PCOS contributes to the observed endometrial dysfunction and that treatment aimed at improving insulin sensitivity and decreasing androgen excess has the potential to reverse identified alterations.To uncover cell-type-specific disease signatures and molecular pathways for PCOS-specific endometrial dysfunction, we first extracted single-nuclei (sn) from frozen endometrial biopsies taken in the proliferative phase (day 7-10) from controls (n=5) and women with PCOS (n=10) at baseline and in PCOS after 16 weeks of metformin (n=7) or lifestyle management (n=3) for snRNA-sequencing. The 10x Genomics protocol allowed us to sequence ≈10,000 nuclei/sample and ≈20,000 reads/nuclei. A total of 248,694 nuclei were captured and 6 major cell types were identified. The 3 largest cell clusters were i) stromal cells (124,055 nuclei), ii) epithelial cells (105,095 nuclei) and iii) immune cells (13,596), whilst iv) uterine smooth muscle cells, v) endothelial and vi) lymphoid cell clusters consisted of <3000 nuclei. Subsetting the epithelial cells revealed the functional luminal, glandular and ciliated cell types as well as proliferative cells. In the immune cell cluster, both myeloid and lymphoid lineage cells were identified, of which uterine NK-cells (uNK) and macrophages (uM) were the largest populations. Several differentially expressed genes (DEGs) of the epithelial subtypes, uNKs, uMs and stromal cells were identified in women with PCOS compared with controls. DEGs in cell types between PCOS cases and controls were enriched in pathways related to cilium organization in the ciliated epithelium, extracellular matrix structure in stromal cells, and cysteine-type endopeptidase activity in uM type 1. Of note, both 16-week of metformin treatment or lifestyle management restored multiple DEGs in each subtype. Second, to validate the identified molecular target, we have established 3D endometrial organoids (EOs) from fresh endometrial biopsies of control and PCOS women. After several passages, EOs were cryopreserved to create a biobank for future functional analyses of the molecular targets. The EOs can be re-established after thawing and immunofluorescence staining shows that the EOs consist of an intact proliferative basolateral epithelial membrane. This rigorous mapping of the human PCOS endometrium improves our understanding of cellular complexity and specific cell types. It provides new mechanistic insights into disease-specific endometrial dysfunction(s), and several of the identified dysfunctions can be reversed by current first-line interventions. Presentation: Friday, June 16, 2023

Differential sensitivity to Wnt signaling gradients in human gastric organoids derived from corpus and antrum.

Wnt signaling regulates gastric stem cell proliferation and differentiation. Although similar Wnt gradients exist within the corpus and antrum of the human stomach, there are striking differences in gland architecture and disease manifestation that suggest Wnt may differentially regulate progenitor cell function in each compartment. In this study, we tested sensitivities to Wnt activation in human gastric corpus and antral organoids to determine whether progenitor cells have region-specific differences in Wnt responsiveness. Human patient-matched corpus and antral organoids were grown in the presence of varying concentrations of the Wnt pathway activator CHIR99021 to assess regional sensitivity to Wnt signaling on growth and proliferation. Corpus organoids were further studied to understand how high Wnt affected cellular differentiation and progenitor cell function. A lower concentration of CHIR99021 stimulated peak growth in corpus organoids compared with patient-matched antral organoids. Supramaximal Wnt signaling levels in corpus organoids suppressed proliferation, altered morphology, reduced surface cell differentiation, and increased differentiation of deep glandular neck and chief cells. Surprisingly, corpus organoids grown in high CHIR99021 had enhanced organoid forming potential, indicating that progenitor cell function was maintained in these nonproliferative, deep glandular cell-enriched organoids. Passaging high-Wnt quiescent organoids into low Wnt rescued normal growth, morphology, and surface cell differentiation. Our findings suggest that human corpus progenitor cells have a lower threshold for optimal Wnt signaling than antral progenitor cells. We demonstrate that Wnt signaling in the corpus regulates a bimodal axis of differentiation, with high Wnt promoting deep glandular cell differentiation and suppressing proliferation while simultaneously promoting progenitor cell function.NEW & NOTEWORTHY This study demonstrates that human gastric corpus organoids have a lower Wnt signaling threshold to drive optimal growth relative to patient-matched antral organoids. Paradoxically, supramaximal Wnt levels suppress corpus organoid proliferation, yet promote differentiation toward deep glandular cell types while simultaneously enhancing progenitor cell function. These findings provide novel insights into how Wnt signaling differentially regulates homeostasis in the human gastric corpus and antrum and contextualizes patterns of Wnt activation diseases.

Aberrant activation of Notch1 signaling in the mouse uterine epithelium promotes hyper-proliferation by increasing estrogen sensitivity.

In mammals, the endometrium undergoes dynamic changes in response to estrogen and progesterone to prepare for blastocyst implantation. Two distinct types of endometrial epithelial cells, the luminal (LE) and glandular (GE) epithelial cells play different functional roles during this physiological process. Previously, we have reported that Notch signaling plays multiple roles in embryo implantation, decidualization, and postpartum repair. Here, using the uterine epithelial-specific Ltf-iCre, we showed that Notch1 signaling over-activation in the endometrial epithelium caused dysfunction of the epithelium during the estrous cycle, resulting in hyper-proliferation. During pregnancy, it further led to dysregulation of estrogen and progesterone signaling, resulting in infertility in these animals. Using 3D organoids, we showed that over-activation of Notch1 signaling increased the proliferative potential of both LE and GE cells and reduced the difference in transcription profiles between them, suggesting disrupted differentiation of the uterine epithelium. In addition, we demonstrated that both canonical and non-canonical Notch signaling contributed to the hyper-proliferation of GE cells, but only the non-canonical pathway was involved with estrogen sensitivity in the GE cells. These findings provided insights into the effects of Notch1 signaling on the proliferation, differentiation, and function of the uterine epithelium. This study demonstrated the important roles of Notch1 signaling in regulating hormone response and differentiation of endometrial epithelial cells and provides an opportunity for future studies in estrogen-dependent diseases, such as endometriosis.

Light Microscopy and Ultrastructure of Body Wall in Leech Haemadipsa zeylanica.

Leeches are widely distributed worldwide in a diversity of habitats, such as freshwater, seas, desert, and oases. Since literature does not have an elaborate study on histology of leeches, thus emphasis is given to study the histology. The aim of this study is to examine the histology of free-living leeches Haemadipsa zeylanica under light microscopy and extended to ultrastructural study under transmission electron microscopy. Tissue was fixed in 10% formalin, dehydrated with alcohol, infiltrated and embedded in wax, and thin section was cut using a rotary microtome. Sections were stained with hematoxylin and eosin. The epithelial layer of cells in H. zeylanica had a thin layer of cuticles covering it. In light microscopy, the epidermis has three types of epidermal cells, namely, glandular cells (Type I, Type II, and Type III), supporting cells (Type IV), and pigment cells (Type V). When the three glandular cells of the body wall of H. zeylanica epidermis were examined under an electron microscope, three types of distinct electron-dense granules were identified. Type I cells with granules, Type II cells with course granules close to the dermis were identified as pear-shaped secretory cells, and Type III cells with electron-dense granules.

Kinorhynchs from sandy coastal habitats in Turkey, with the description of a new pan- Mediterranean species of Echinoderes (Cyclorhagida: Echinoderidae)

Kinorhynchs from eight sandy, shallow water localities along the west and south coasts of Turkey were examined. The study resulted in the finding of six different species: Two species, Echinoderes gerardi and Cephalorhyncha flosculosa were known from Turkey, two species, Echinoderes riedli and Campyloderes vanhoeffeni were known from the Mediterranean, but are new to Turkey, and two species, Echinoderes sp. and E. shahmaranae sp. nov. are new to science. Echinoderes sp. resembles E. charlotteae from the Gulf of Mexico, but differs at some minor points. However, since only a single specimen was available, only diagnostic details, but no formal description, is provided. Echinoderes shahmaranae sp. nov. is described from Muğla. The species is distinguished by its unique combination of spine; tube and glandular cell type 2 distributions, as well as the presence of conspicuous, rigid, paraventral cuticular hairs. The latter character was evaluated across all echinoderid species from which information was available. It is present in only sixteen other echinoderid species, and is considered to be a character of potential phylogenetic significance. Other morphological findings include the confirmed lack of paradorsal sensory spots on segments 4 and 5, and presence of a middorsal fissure on segment 11 in C. flosculosa.

A novel epidermal gland type in lizards (α-gland): structural organization, histochemistry, protein profile and phylogenetic origins

AbstractChemical signalling is an essential component of the communication system of lizards, and epidermal glands are responsible for producing semiochemicals that regulate many behavioural interactions. Two types of epidermal glands have been previously described for lizards: follicular and generation glands. Generation glands are characterized by the aggregation of novel glandular cell types in the epithelium and the lack of a lumen or external pore. Despite the fact that several subtypes of generation glands have been recognized over the years, the morphology, taxonomic distribution, function and evolutionary origins of generation glands remain nearly unexplored in Neotropical clades. Here, we describe a novel escutcheon-type generation gland (‘α-gland’) for lizards of the South American family Tropiduridae, characterize its structural and ultrastructural organization, and study the homology of the constituent parts in a phylogenetic framework. The α-glands emerged in the ancestor of Eurolophosaurus, Plica, Strobilurus, Tropidurus and Uracentron, and are found in at least 39 species with diverse ecological habits. We preliminarily analysed the protein profile of α-glands and discovered differential expression of protein components between sexes. Our investigations change the general view about epidermal gland homology, leading us to argue that generation and follicular glands are possibly more closely related functionally and evolutionarily than previously thought.

Classification of Glandular Cells using a Pre-trained Convolutional Neural Network

Tissues can be divided into glandular structures (cells) and non-glandular when we magnify them with a microscope. To classify the two types, we performed experiments using convolutional neural network. We cropped regions of glandular cells and non-glandular in 10 x magnification images. The size of cropped images was between 80 and 100 pixels in width and height. We prepared 932 glandular cells and 1000 non-glandular for the train and test. Of these, 1468 were used for learning and 532 were used for testing. We trained and tested the dataset using a slightly modified pre-trained VGG16. The inside of glandular cells consists of nucleus, lumen and cytoplasm. Normal glandular cells and abnormal glandular cells that we call tubular adenoma have different texture features. But both types of glandular cells have distinct boundaries and specific shapes. In the case of cancer, as the nucleus grows excessively, the boundaries of the glandular cells become unclear and disappear. We trained three types of glandular cells, which is normal, tubular adenoma, and cancer. Experimental results using the pre-trained VGG16 classification showed a high classification accuracy of 99.44%. Only three non-glandular out of the 532 test data were misclassified into glandular cells. The classification method presented in the paper can be used to eliminate false positives that produced by an automatic segmentation system for the pathology image. The performance of the segmentation can be improved by eliminating segmented objects that are false positives.

Anatomical and histochemical features of the digestive system of Octopus vulgaris Cuvier, 1797 with a special focus on secretory cells

AbstractThis study reports a detailed anatomical and histological study of the digestive system of Octopus vulgaris. Emphasis was placed on characterising the glands and glandular cells and their distribution throughout the digestive tract. The use of classic histological and histochemical techniques revealed two morphological types of glandular cells: granular and mucous. Moreover, the histochemical analysis indicated specialisation of mucous glandular cells in the buccal mass, the submandibular gland and the caecum for secreting acid and neutral glycoconjugates. The cells of the anterior salivary glands are specialised for secreting neutral glycoproteins, and those of the posterior salivary glands are specialised for granular and mucous secretion. The oesophagus, crop and stomach lack glandular cells, but both granular and mucous glandular cells are found in the intestine. An unusual structure resembling the typhlosole of bivalves is described for the first time in the intestine of O. vulgaris. The highly ciliated epithelium and location of the structure in the anterior part of the intestine suggest a possible role in bypassing the caecum, stomach and intestine. We discuss how these cells and organs contribute to the process of digestion in the light of the present histological and histochemical data and of previously published information on the morphology and physiology of digestion in the octopus.

Current State of Knowledge on Salivary Gland Cancers.

Salivary gland cancers (SGCs), categorized as head and neck cancers (HNCs), constitute about 6% of head and neck cancer diagnoses based on estimate by American Head and Neck Society. Salivary gland tumors originate from different glandular cell types and are thus morphologically diverse. These tumors arise from any of the three major and various minor salivary glands. The incidence of SGCs has slowly increased during the last four decades. The etiology of SGCs is mostly unknown; however, specific gene mutations are associated with certain types of salivary tumors. Treatment options include surgical resection, radiation therapy (RT), chemotherapy, and multimodality therapy. HNC patients treated with RT often develop xerostomia and salivary hypofunction due to damaged salivary glands. In this review, we discuss etiology of SGCs, present findings on the role of autophagy in salivary tumorigenesis, review adverse effects of radiation treatment, and examine remedies for restoration of salivary function.

IMP3 overexpression occurs in various important cancer types and is linked to aggressive tumor features: A tissue microarray study on 8,877 human cancers and normal tissues.

IMP3 is an RNA binding protein required for ribosomal RNA processing, which has been suggested to be a prognostic marker in a large variety of human types of cancer. However, available data on the prevalence of IMP3 expression are largely discrepant. To systematically investigate the epidemiology and clinical relevance of IMP3 expression in human cancers we employed a two-step tissue microarrays (TMAs) approach. First, a normal tissue TMA and a multi-tumor TMA were analyzed for immunohistochemically detectable expression of IMP3 in 76 different normal tissue types and 3889 cancer samples from 95 different tumor categories. In a second step, we searched for associations between IMP3 expression and tumor phenotype and patient prognosis in TMAs containing 697 urinary bladder cancers, 1711 colon cancers, 343 esophageal adenocarcinomas, 251 esophageal squamous cell cancers, 673 lung cancers), 275 pancreatic cancers and 230 stomach cancers. In normal tissues, unequivocal IMP3 expression was found in placenta, lymphocytes and some types of glandular epithelial cells. In cancers, at least one case with weak expression could be found in 76 out of 95 (80%) different tumor types and 64 entities (67%) had at least one tumor with strong positivity. IMP3 expression was most frequently found in testicular cancer (including 71% seminomas and 96% non-seminomas), neuroblastoma (88%), and squamous cell cancer of various origins. Significant associations were found between IMP3 and adverse tumor features in esophageal adenocarcinomas and cancers of the urinary bladder, lung, stomach, and pancreas. In summary, IMP3 was frequently expressed in many different tumor types, and was typically associated with aggressive tumor features.

Multipotent Myoepithelial Progenitor Cells Are Born Early during Airway Submucosal Gland Development.

Airway submucosal glands (SMGs) are facultative stem cell niches for the surface epithelium, but the phenotype of the SMG-derived progenitor cells remains unclear. In other organs, glandular myoepithelial cells (MECs) have been proposed to be multipotent progenitors for luminal cells. We sought to determine the developmental phase during which mouse tracheal glandular MECs are born and whether these MECs are progenitors for other cell phenotypes during SMG morphogenesis. To approach this question, we localized two MEC protein markers (α-smooth muscle actin [αSMA/ACTA2] and smooth muscle myosin heavy chain 11 [SMMHC/MYH11]) during various stages of SMG development (placode, elongation, branching, and differentiation) and used ACTA2-CreERT2 and MYH11-CreERT2 transgenic mice to fate map MEC-derived lineages during SMG morphogenesis. Both αSMA- and SMMHC-expressing cells emerged early after placode formation and during the elongation phase of SMG development. Lineage tracing in newborn mice demonstrated that lineage-positive MECs are born at the tips of invading tubules during the elongation phase of gland development. Lineage-positive MECs born within the first 7 days after birth gave rise to the largest percentage of multipotent progenitors capable of contributing to myoepithelial, serous, mucous, and ductal cell lineages. Serial tamoxifen-induction of both Cre-driver lines demonstrated that lineage-positive multipotent MECs contribute to ∼ 60% of glandular cells by 21 days after birth. In contrast, lineage-traced MECs did not contribute to cell types in the surface airway epithelium. These findings demonstrate that MECs born early during SMG morphogenesis are multipotent progenitors with the capacity to differentiate into other glandular cell types.

Ultrastructure of male accessory glands in the scorpionfly Sinopanorpa tincta (Navás, 1931) (Mecoptera: Panorpidae)

The ultrastructure of male reproductive accessory glands was investigated in the scorpionfly Sinopanorpa tincta (Navás, 1931) (Mecoptera: Panorpidae) using light and transmission electron microscopy. The male accessory glands comprise one pair of mesodermal glands (mesadenia) and six pairs of ectodermal glands (ectadenia). The former opens into the vasa deferentia and the latter into the ejaculatory sac. The mesadenia consist of a mono-layered elongated columnar epithelium, the cells of which are highly microvillated and extrude secretory granules by means of merocrine mechanisms. The epithelium of ectadenia consists of two types of cells: the large secretory cells and the thin duct-forming cells. These two types of cells that join with a cuticular duct constitute a functional glandular unit, corresponding to the class III glandular cell type of Noirot and Quennedey. The cuticular duct consists of a receiving canal and a conducting canal. The secretory granules were taken up by the receiving canal and then plunged into the lumen through the conducting canal.

Exoskeletons of Bougainvilliidae and other Hydroidolina (Cnidaria, Hydrozoa): structure and composition.

The exoskeleton is an important source of characters for the taxonomy of Hydroidolina. It originates as epidermal secretions and, among other functions, protects the coenosarc of the polypoid stage. However, comparative studies on the exoskeletal tissue origin, development, chemical, and structural characteristics, as well as its evolution and homology, are few and fragmented. This study compares the structure and composition of the exoskeleton and underlying coenosarc in members of “Anthoathecata” and some Leptothecata, but does so mainly in bougainvilliid polyps histological analyses. We also studied the development of the exoskeleton under experimental conditions. We identified three types of glandular epidermal cells related to the origin of the exoskeleton and the secretion of its polysaccharides component. The exoskeleton of the species studied is either bilayered (perisarc and exosarc, especially in bougainvilliids) or corneous (perisarc). The exoskeleton varies in chemical composition, structural rigidity, thickness, extension, and coverage in the different regions of the colony. In bilayered exoskeletons, the exosarc is produced first and appears to be a key step in the formation of the rigid exoskeleton. The exoskeleton contains anchoring structures such as desmocytes and “perisarc extensions.”

Significance of high-risk HPV detection in women with atypical glandular cells on Pap testing: Analysis of 1857 cases from an academic institution.

The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined. Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013. Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results. The overall rate of hrHPV positivity (hrHPV+) was 27.7%. Of these 2287 cases, 1857 cases (81.2%) had histological follow-up results within 1 year, including 529 hrHPV + cases and 1328 hrHPV-negative (hrHPV-) cases. Among the hrHPV + cases, 16.8% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 5.7% had cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 1.1% had an endometrial carcinoma. Among the hrHPV- cases, 0.6% had CIN2/3, 0.2% had AIS/ADC, and 3.8% had an endometrial carcinoma. The rate of high-grade cervical lesions (CIN2/3, AIS, or ADC) was significantly higher in women who were hrHPV + compared with hrHPV- women for all age groups. Endometrial carcinoma was most commonly present in women aged ≥50 years. To the authors' knowledge, the current study is the largest follow-up study published to date regarding women with AGC cytology and HPV testing. The study data indicate that hrHPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with AGC, but has no significant value in evaluating the risk of endometrial carcinoma. The combination of cytology, hrHPV testing, and patient age can significantly aid in the appropriate management of these individuals. Cancer Cytopathol 2017;125:205-211. © 2016 American Cancer Society.

Coupled cell networks are target cells of inflammation, which can spread between different body organs and develop into systemic chronic inflammation.

Several organs in the body comprise cells coupled into networks. These cells have in common that they are excitable but do not express action potentials. Furthermore, they are equipped with Ca2+ signaling systems, which can be intercellular and/or extracellular. The transport of small molecules between the cells occurs through gap junctions comprising connexin 43. Examples of cells coupled into networks include astrocytes, keratinocytes, chondrocytes, synovial fibroblasts, osteoblasts, connective tissue cells, cardiac and corneal fibroblasts, myofibroblasts, hepatocytes, and different types of glandular cells. These cells are targets for inflammation, which can be initiated after injury or in disease. If the inflammation reaches the CNS, it develops into neuroinflammation and can be of importance in the development of systemic chronic inflammation, which can manifest as pain and result in changes in the expression and structure of cellular components. Biochemical parameters of importance for cellular functions are described in this review.

Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known. To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis. Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration. This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.

Identifying Three Ecological Chemotypes of Xanthium strumarium Glandular Trichomes Using a Combined NMR and LC-MS Method

Xanthanolides, as the sesquiterpene lactones, are reportedly the major components for the pharmacological properties of X. strumarium L. species. Phytochemical studies indicated that the glandular structures on the surface of plant tissues would form the primary sites for the accumulation of this class of the compounds. As the interface between plants and their natural enemies, glandular trichomes may vary with respect to which of their chemicals are sequestered against different herbivores in different ecologies. However, to date, no data are available on the chemical characterisation of X. strumarium glandular cells. In this study, the trichome secretions of the X. strumarium species originating from nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC-ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium glandular trichomes were discovered along with the qualitative and quantitative evaluations of their presence of xanthanolides; these were designated glandular cell Types I, II, and III, respectively. The main xanthanolides in Type I cells were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8-epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of each being present. For Type III cells, significantly higher concentrations of 8-epi-xanthatin or xanthinosin (relative to xanthatin) were detected with xanthinosin only being observed in this type. Further research will focus on understanding the ecological and molecular mechanism causing these chemotype differences in X. strumarium glandular structures.

GLP-1 Receptor Is Expressed in Human Stomach Mucosa

The stomach is a target organ of the incretin hormone glucagon-like peptide-1 (GLP-1). However, the cellular expression and glandular distribution of its receptor (GLP-1R) in human gastric mucosa are not known. We determined the expression of GLP-1R in different regions of human stomach mucosa and its specific cellular association and distribution within gastric glands. Tissue samples from stomach body and antrum were obtained from 20 patients during routine esophagogastroduodenoscopy. mRNA encoding GLP-1R protein expression was evaluated by RT-PCR. Determination of cell types bearing GLP-1R, their localization, and their frequency in gastric glands in different gastric regions were estimated by immunohistochemical morphological analysis. Levels of GLP-1R mRNA were similar in body and antrum. GLP-1R immunoreactivity was found throughout the gastric mucosa in various types of glandular cells. The highest frequency of GLP-1R immunoreactive cells was found in the neck area of the principal glands in cells morphologically identified as parietal cells. GLP-1R immunostaining was also found on enteroendocrine-like cells in the pyloric glands. This study provides the first description of GLP-1R expression in human gastric glands and its specific cellular association. Our data suggest that GLP-1 may act directly on the gastric mucosa to modulate its complex functions.