Endothelial Cells Of Blood Vessels Research Articles

Assessment of the cellular localisation of the annexin A2/S100A10 complex in human placenta

The AnxA2/S100A10 complex has been implicated in various placental functions but although the localisation of these proteins individually has been studied, there is no information about the localisation of their complex in situ at the cellular level. Using the proximity ligation technique, we have investigated the in situ localisation of AnxA2/S100A10 complex in the placenta and have compared this with the location patterns of the individual proteins. High levels of expression of AnxA2/S100A10 complexes were observed in the amniotic membrane and in blood vessel endothelial cells. Lower levels were detected in the brush border area of the syncytium and in the trophoblasts. Immunohistochemical analysis of AnxA2 and S100A10 individually revealed broadly similar patterns of localisation. The brush border staining pattern suggests that in this location at least some of the AnxA2 is not in complex with S100A10. The formal location of the AnxA2/S100A10 complex is compatible with a role in cell–cell interaction, intracellular transport and secretory processes and regulation of cell surface proteases, implying contributions to membrane integrity, nutrient exchange, placentation and vascular remodelling in different parts of the placenta. Future applications will allow specific assessment of the association of the complex with pathophysiological disorders.

Near-physiological microenvironment simulation on chip to evaluate drug resistance of different loci in tumour mass

Developing a bio-functional model in vitro to study cancer resistance, which is a big challenge for clinical cancer therapy, is of great interest. Such reliable model requires appropriate drug diffusion kinetics simulation and a microenvironment that allows cell-cell and cell-matrix interactions. In this work, a special hydrogel-based three-dimensional (3D) microfluidic chip was constructed to simulate tumour-vascular microenvironment. The self-healing hydrogel supports long-time cell survival and proliferation, effective cellular metabolism of cancer drugs and cell-cell interaction between different types of cells. In the effective near-physiological tumour-vascular microenvironment, the endothelial and fibroblast cells are spread on different sides of a porous membrane, while sensitive and resistant breast tumour cells are separately cultured in the dynamic hydrogel consisting of glycol chitosan and telechelic difunctional poly (ethylene glycol) in the upper chambers. Nutrients and drugs are introduced through the bottom channel and diffuse into the cancer cells. Doxorubicin molecules pass first through blood vessel endothelial cells and act on the tumour cells surrounded by fibroblasts. Tumour cells respond differently to drug when they are cultured in the microenvironment. Sensitive breast tumour cells have a 47% increase in viability than those cultured without fibroblasts and endothelial cells. Both sensitive and resistant tumour cells can be analysed under the same chemical environment. This work represents a multi-functional in vitro platform that allows near-physiological simulation, effective drug metabolism and cellular response to extracellular stimuli and has great potential to make drug discovery speedy and precise.

Nogo‑B receptor in relevant carcinoma: Current achievements, challenges and aims (Review)

The novel neurite outgrowth inhibitorB (Nogo‑B) receptor (NgBR) is specific for Nogo‑B, which is highly expressed in various human organs and cells, including the lung, liver, kidney, smooth muscle cells, blood vessel endothelial cells and inflammatory cells. Previous studies have indicated that NgBR directly interacts with Nogo‑B and is able to independently influence lipid and cholesterol homeostasis, angiogenesis, N‑glycosylation, the epithelial-mesenchymal transition, the chemotaxis of endothelial cells and cellular proliferation and apoptosis. These multiple functions and actions of this receptor provide an understanding of the important roles of NgBR in various conditions, including fatty liver, atherosclerosis, intracranial microaneurysms, retinitis pigmentosa and severe neurological impairment. Furthermore, NgBR has been demonstrated to exert protean, multifunctional and enigmatic effects in cancer. The present review summarizes the latest knowledge on the suppressing and activating effects of NgBR, emphasizing its function in cancer. Further basic and medical research on this receptor may provide novel insight into its clinical implications on the prognosis of relevant human cancer types.

Enhanced expression of IL-34 in an inflammatory cyst of the submandibular gland: a case report

BackgroundCysts of the salivary glands are common lesions that occur in the context of various etiologies. Although the diagnostic importance of cysts in salivary gland diseases has been well studied, molecular mechanisms that control the related pathological process remain largely unknown. IL-34 is a novel cytokine that was discovered recently as a tissue-specific ligand of colony stimulating factor-1 receptor. Since its discovery, accumulating evidence has revealed emerging roles of IL-34 in various pathological conditions and has been suggested to correlate remarkably with inflammation. In this study, we report a medical case of an inflammatory cyst within the submandibular gland, through which evaluating the possible involvement of IL-34 in salivary gland disorders.Case presentationA 37-year-old male patient suffered from a sudden swelling in the right submandibular region, started initially small and had gradually increased in size to reach 3–4 cm in 1 week, accompanied by pain and local fever. Ultrasonography and MRI imaging revealed the existence of a well-defined cystic lesion with sharp borders measuring 39.8 mm × 19.7 mm within the right submandibular gland. The cyst was removed surgically, and the diagnostic decision was determined based on histopathological observations as an inflammatory cyst in the submandibular gland. Sections were generated from different regions of the surgically resected inflammatory cyst and used to examine IL-34 expression by immunohistochemistry compared to normal salivary gland tissues. Immunohistochemical staining showed enhanced expression of IL-34 in the ductal epithelial cells and endothelial cells of blood vessels, with a tendency to be accompanied with high infiltration of immune cells, which suggests a possible involvement of IL-34 in the pathogenesis of salivary gland inflammation.ConclusionsIn this report, we introduce interesting findings of enhanced IL-34 expression in a case of an inflamed submandibular gland. Our findings emphasize the pathological roles of IL-34 as an inflammation amplifier and angiogenic enhancer in inflammatory conditions, such as in salivary gland disorders.

The potential role of CD31 and Bcl-2 in the etiopathogenesis of oral pyogenic granuloma

Pyogenic granuloma (PG) is a vascular reactive lesion of the oral cavity which is caused by local trauma or irritation and has a distinct biological behavior. Up till now, the pathogenesis of PG is not adequately understood. Aim: Assessment of the expression of CD31 and Bcl-2 in PG to clarify the etiopathogenesis of this lesion and to determine whether vascular proliferation in this lesion has a relation to its apoptotic status. Materials and Methods: 4μm sections were prepared from paraffin-embedded blocks of PG (20 samples) and normal gingiva as a control (10 samples). Staining of each specimen with hematoxylin and eosin (H&E), CD31 and Bcl-2 was done. Results: all lesions of PG showed positive CD31 and Bcl-2 immunostaining in the endothelial cells of blood vessels and in the stromal ovoid cells. Control group showed positive CD31expression in the endothelial cells of blood vessels while Bcl-2 expression revealed positive expression mainly in the basal cells of the epithelium. A significant higher expression of CD31 and Bcl-2 was detected in PG than normal gingiva. A strong positive correlation was found between CD31 and Bcl-2 area percent of immune-expression. Conclusions: The data of the present study suggest a role of Bcl-2 overexpression in the potentiation of angiogenic response and support the role of CD31 and Bcl-2 in the etiopathogenesis of PG.

A crystal structure of coil 1B of vimentin in the filamentous form provides a model of a high-order assembly of a vimentin filament.

Structural data are available in the PDB under the accession number 5WHF.

Abnormal dartos fascia in buried penis and hypospadias: Evidence from histopathology

The importance of the pathology of the dartos fascia in hypospadias and buried penis is still debatable. Understanding the properties of connective tissue of dartos fascia in hypospadias and buried penis may give a clue to the underlying mechanism. This study aimed to compare connective tissue and vascularization of dartos fascia between normal penis, buried penis, and hypospadias. We conducted this prospective study from May 2013 to November 2016. We collected dartos fascia specimens from three groups: buried penis, hypospadias, and normal penis as control. All of the patients underwent primary surgery in all groups. Patients with penile abnormalities, such as phimosis or Balanitis Xerotica Obliterans (BXO) were excluded from the normal penis group. We compared the fibers between these groups using Masson trichrome histochemical staining, Gomori's silver impregnation staining, Weigert resorcin-fuchsin staining, and CD31 immunohistochemistry staining for evaluation of collagen fibers, reticulin fibers, elastin fibers, and endothelial cells of blood vessels, respectively. The collagen fibers, reticular fibers, elastic fibers, and vascular vessels were counted with ImageJ and manually calibrated and counted and were analyzed using the one-way ANOVA test. The assessment conducted by two pathologists was blinded, without knowing the clinical diagnosis of patients. There was a total of 60 patients with 20 patients in each group. Collagen fibers for most cases of buried penis and hypospadias showed thicker but fewer collagen fibers than the normal penis. There was a reduction of total collagen and elastin of dartos fascia in hypospadias and buried penis cases. On the other hand, the ratio of reticulin fibers, which represents collagen type III to total collagen, was increased compared to normal penis. Although the dartos fascia in buried penis and hypospadias is thick and inelastic when palpated or during traction/counter traction, it is well-vascularized tissue. This inelastic dartos fascia tissue is an abnormal tissue, but its characteristics are not similar to fibrotic tissue. However, further study with a larger sample is warranted and should differentiate the degree of chordee in patients with hypospadias and buried penis. There was a difference between connective the tissue of dartos fascia in buried penis and patients with hypospadias compared with normal penis. Inelastic dartos fascia tissue in patients diagnosed with buried penis and hypospadias is an abnormal tissue. Therefore, it is suggested that this tissue is excised during reconstructive surgery. Further research is needed to unveil the pathophysiology of the condition.

Proapoptotic Cyclic Peptide BC71 Targets Cell-Surface GRP78 and Functions as an Anticancer Therapeutic in Mice

Glucose regulated protein 78 kDa (GRP78) is a recently emerged target for cancer therapy and a biomarker for cancer prognosis. Overexpression of GRP78 is observed in many types of cancers, with the cell-surface GRP78 being preferentially present in cancer cells and cancer blood vessel endothelial cells. Isthmin (ISM) is a secreted high-affinity proapoptotic protein ligand of cell-surface GRP78 that suppresses angiogenesis and tumor growth in mice. The C-terminal AMOP (adhesion-associated domain in MUC4 and other proteins) domain of ISM is critical in mediating its interaction with human umbilical vein endothelial cells (HUVECs). In this work, we report novel cyclic peptides harboring the RKD motif in the ISM AMOP domain that function as proapoptotic ligands of cell-surface GRP78. The most potent peptide, BC71, binds to GRP78 and converge to tumor in mice. Intravenous administration of BC71 suppressed xenograft tumor growth in mice as a single agent, with significant reduction in tumor angiogenesis and upsurge in apoptosis. Fluorescent-labeled BC71 accumulates in tumor in mice by targeting cell-surface GRP78. We show that BC71 triggers apoptosis via cell-surface GRP78 and activates caspase-8 and p53 signaling pathways in HUVECs. Using amide hydrogen-deuterium exchange mass spectrometry (HDXMS), we identified that BC71 preferentially binds to ATP-bound GRP78 via amino acid residues 244–257 of GRP78. Hence, BC71 serves as a valuable prototype for further development of peptidomimetic anticancer drugs targeting cell-surface GRP78 as well as PET imaging agents for cancer prognosis.

Generation, characterization and application of monoclonal antibodies against matrix protein of hirame novirhabdovirus (HIRRV) in flounder.

Hirame novirhabdovirus (HIRRV) causes severe disease in fish cultures, resulting in great economic loss in Asia and Europe. In this study, the matrix protein (M) of HIRRV was recombinantly expressed as the immunogen to produce monoclonal antibodies (MAbs) using hybridoma cell fusion technology, and 3 MAbs were produced and characterized by indirect ELISA, Western blotting and immunofluorescence assay (IFA). Western blotting and mass spectrometric analysis showed that the MAbs could specifically react with the nature M protein of HIRRV. The MAbs were employed to detect virions in HIRRV-infected epithelioma papulosum cyprini (EPC) cells and flounder Paralichthys olivaceus by IFA and immunohistochemistry (IHC). In the virus-infected EPC cells, the virions were mainly located in the cytoplasm, whereas in flounder, HIRRV was present in all 10 tested tissues, and the positive signals in spleen, head-kidney and heart were higher than in other tissues, consistent with the results obtained by RT-PCR. Moreover, strong positive signals were observed in the endothelial cells of blood vessels, but only the leukocytes were infected by HIRRV in the whole blood cells. These results indicate that the high susceptibility to HIRRV of leukocytes and endothelial cells may facilitate the spread of HIRRV and finally cause systemic infection in flounder. This study provides a foundation for further studies on rapid diagnosis of HIRRV and its infection mechanisms.

Vascularization of the Damaged Nerve under the Effect of Experimental Cell Therapy.

Quantitative analysis of blood vessels in the distal segment of rat sciatic nerve after its ligation for 40 sec and subperineurial administration of mesenchymal stem cells or dissociated cells of rat embryonic spinal cord was carried our by immunohistochemical tracing of von Willebrand factor, a marker of endothelial cells of blood vessels. It was found that the number of blood vessels per unit area of the nerve trunk in 21 days after injury and administration of mesenchymal stem cells increased by more than 1.5 times in comparison with the control (damaged nerve). After administration of dissociated cells of the embryonic spinal cord, this effect was not observed. It is assumed that mesenchymal stem cells stimulate the growth of vessels of the damaged nerve via production of angiogenic factors.

Effectiveness of Vascular Markers (Immunohistochemical Stains) in Soft Tissue Sarcomas.

To ascertain the effectiveness of IHC markers of vascular origin like CD31, CD34, FLI1 and ERG in vascular soft tissue sarcomas including angiosarcomas, Kaposi sarcomas, epithelioid hemangioendothelioma and a non-vascular soft tissue sarcoma (Epithelioid sarcoma). Descriptive study. Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from 2011 to 2017. Diagnosed cases of angiosarcomas (n=48), epithelioid hemangioendothelioma (n=9), Kaposi sarcoma (n=9) and epithelioid sarcoma (n=20) were selected. Immunohistochemical staining as performed on formalin fixed paraffin embedded sections. The sections were stained for the following markers: CD34 (VENTANA clone Q Bend 10), CD31 (Leica clone 1 A 10), FLI1 (CELL MARQUE clone MRQ-1) and ERG (CELL MARQUE clone EP111). A complete panel of CD34, CD31 and ERG was applied on 8/48 cases of angiosarcomas with triple positivity in 6 cases. Eight cases showed positivity for only CD31 and ERG and 2 cases showed positivity for only ERG. A complete panel of CD34, CD31 and ERG was applied on 3/9 cases of epithelioid hemangioendothelioma with positivity for all markers in 2 cases. Combined positivity for ERG and CD34 was seen in 2 cases and on 4 cases only CD31 immunohistochemical was solely applied with 100% positivity. FLI1 was not applied on any case. Among 9 cases of Kaposi sarcoma, ERG, CD34 and CD31 in combination were applied on only 1 case with triple positivity. Remaining cases show positivity for either CD34, CD31 or FLI1. Majority of cases of epithelioid sarcomas were diagnosed on the basis of cytokeratin and CD34 positivity with loss of INI1. The other vascular markers showed negativity in all cases. Among these four markers, ERG immunohistochemical stain is highly effective for endothelial differentiation due to its specific nuclear staining pattern in normal blood vessel endothelial cells (internal control) as well as neoplastic cells of vascular tumors and lack of background staining.

Expression and significance of the Hedgehog signal transduction pathway in oxygen-induced retinal neovascularization in mice.

AimThe aim of the study was to investigate the signal transduction mechanism of Hedgehog–vascular endothelial growth factor in oxygen-induced retinopathy (OIR) and the effects of cyclopamine on OIR.MethodsAn OIR model was established in C57BL/6J mice exposed to hyperoxia. Two hundred mice were randomly divided into a control group, an OIR group, an OIR-control group (treated with isometric phosphate-buffered saline by intravitreal injection), and a cyclopamine group (treated with cyclopamine by intravitreal injection), with 50 mice in each group. The retinal vascular morphology was observed using adenosine diphosphatase and number counting using hematoxylin and eosin-stained image. Quantitative real-time quantitative polymerase chain reaction was used to detect mRNA expression. Protein location and expression were evaluated using immunohistochemistry and Western blot.ResultsThe OIR group and OIR-control group demonstrated large-area pathological neovascularization and nonperfused area when compared with the control group (both P<0.05). The area of nonperfusion and neovascularization in the cyclopamine group was significantly reduced compared with the OIR and OIR-control groups (both P<0.05). Compared with the control group, the OIR and OIR-control groups had more vascular endothelial cells breaking through the inner limiting membrane. The number of new blood vessel endothelial cell nuclei in the cyclopamine group was significantly reduced (both P<0.05) when compared with the OIR and OIR-control groups. The mRNA and protein expressions of Smoothened, Gli1, and vascular endothelial growth factor in the signal pathway of the OIR and OIR-control groups were significantly higher than those of the control group; however, in the cyclopamine group, these factors were reduced when compared with the OIR and OIR-control groups (all P<0.05).ConclusionOur data suggest that abnormal expression of the Hedgehog signaling pathway may be closely associated with the formation of OIR. Inhibiting the Smoothened receptor using cyclopamine could control retinal neovascularization, providing new ideas and measures for the prevention of oxygen-induced retinal neovascularization.

Novel Heparin Receptor Transmembrane Protein 184A is Involved in Maintaining Proper Endothelial Cell Responses to Laminar Flow

Endothelial cells (ECs) comprise the innermost layer of blood vessels and serve numerous critical roles in the vasculature, including nutrient delivery, gas exchange, leukocyte trafficking, and immunological surveillance. Additionally, ECs of blood vessels are constantly exposed to fluid shear stress (FSS) in the form of blood flow, and maintain vessel tone by sensing and responding to FSS through a process called mechanotransduction. Mechanotransduction in ECs is a complex biological process that involves several key adherens junction proteins, such as PECAM‐1, VE‐cadherin, and the vascular endothelial growth factor (VEGF) receptor, VEGFR2. There also exist many other proteins that act as co‐factors to regulate mechanotransduction, such as integrins and heparan sulfate proteoglycans (HSPGs). ECs typically respond to the mechanical forces of laminar (normal) FSS by aligning in the direction of flow, elongating, and maintaining communication at adherens junctions between cells. These responses constitute endogenous atheroprotective mechanisms that ECs use to prevent abnormal vascular physiology. Additionally, regions of the vasculature exposed to laminar blood flow have higher levels of the vasodilator nitric oxide (NO), an important vascular signaling molecule that is produced by endothelial nitric oxide synthase (eNOS). Improper mechanosensing, combined with chronic inflammation or disturbed FSS, can lead to EC dysfunction, which accumulates over time and results in the progression of vascular diseases such as atherosclerosis. Our laboratory recently identified Transmembrane Protein 184A (TMEM184A) as a heparin receptor in vascular cells. Moreover, we have since found that TMEM184A is a modulator of vascular regeneration in vivo. Here, we present evidence that TMEM184A is also involved in EC responses to FSS that prevent dysfunction. Immunofluorescence and immunoprecipitation data collectively suggest that TMEM184A colocalizes and interacts with the classical mechanosensors, several of the HSPGs, and eNOS on the surface of static ECs. Under laminar FSS, TMEM184A colocalization with VE‐cadherin and VEGFR2 is even more apparent. Degradation of endogenous heparan sulfates with heparinase drastically changes typical EC responses to laminar FSS by altering the normal pattern of TMEM184A accumulation in response to shear and impairing EC elongation and alignment. Both of these responses are partially recovered by the addition of heparin. ECs that overexpress TMEM184A have enhanced VE‐cadherin expression at adherens junctions after acclimation to laminar FSS. Treatment of ECs with VEGF to stimulate VEGFR2 produces substantial changes in TMEM184A dynamics and internalization under FSS conditions. Together, these data support a role for TMEM184A in mediating EC responses to laminar flow. Further research is necessary to confirm this role for the heparin receptor in order to assess potential applications for the treatment of cardiovascular disease.Support or Funding InformationNIH HL54269This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Mechanosensitive GPCR that Detects the Bloody Force

Mechanoreceptors mediate a wide variety of physiological processes, such as hearing, touch, proprioception, and blood flow regulation. It is generally believed that mechanoreceptors are force-gated ion channels. Now, Xu etal. uncover a GPCR that is activated by shear force in endothelial cells of blood vessels.

Hemangiossarcoma renal unilateral em cão

O hemangiossarcoma e um tumor mesenquimal maligno com origem nas celulas endoteliais dos vasos, podendo ser primario em qualquer tecido. As neoplasias renais, pos sua vez, sao raras, podendo causar sinais locais ou sistemicos de insuficiencia renal. Um canino da raca boxer, com cinco anos de idade e 24kg foi atendido no Hospital Veterinario Vicente Borelli (HOVET) da Fundacao de Ensino Octavio Bastos (UNIFEOB), com historico de hiporexia, emese e cansaco facil. Ao exame ultrassonografico, constatou-se a presenca de uma massa dorsal no rim direito e de estruturas anecoicas mal definidas no baco. Procedeu-se laparotomia exploratoria com retirada da massa renal e realizacao de nefrectomia, esplenectomia e ovariosalpingohisterectomia. O material retirado adjacente ao rim foi identificado como hemangiossarcoma renal, todavia os demais orgaos nao apresentaram celulas neoplasicas. Apesar da bibliografia afirmar que frequentemente as neoplasias renais malignas tem envolvimento bilateral, no animal em questao, isso nao ocorreu, sendo o objetivo do presente trabalho relatar essa apresentacao incomum de hemangiossarcoma.

Whole-mount Confocal Microscopy for Adult Ear Skin: A Model System to Study Neuro-vascular Branching Morphogenesis and Immune Cell Distribution.

Here, we present a protocol of a whole-mount adult ear skin imaging technique to study comprehensive three-dimensional neuro-vascular branching morphogenesis and patterning, as well as immune cell distribution at a cellular level. The analysis of peripheral nerve and blood vessel anatomical structures in adult tissues provides some insights into the understanding of functional neuro-vascular wiring and neuro-vascular degeneration in pathological conditions such as wound healing. As a highly informative model system, we have focused our studies on adult ear skin, which is readily accessible for dissection. Our simple and reproducible protocol provides an accurate depiction of the cellular components in the entire skin, such as peripheral nerves (sensory axons, sympathetic axons, and Schwann cells), blood vessels (endothelial cells and vascular smooth muscle cells), and inflammatory cells. We believe this protocol will pave the way to investigate morphological abnormalities in peripheral nerves and blood vessels as well as the inflammation in the adult ear skin under different pathological conditions.

MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer growth.

Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins are characterized by the lack of fixed or stable tertiary structure, and are increasingly recognized as an important class of proteins with major roles in signal transduction and transcriptional regulation. In this study, we report the identification and functional characterization of a previously uncharacterized protein (UPF0258/KIAA1024), major intrinsically disordered Notch2-associated receptor 1 (MINAR1). While MINAR1 carries a single transmembrane domain and a short cytoplasmic domain, it has a large extracellular domain that shares no similarity with known protein sequences. Uncharacteristically, MINAR1 is a highly IDP with nearly 70% of its amino acids sequences unstructured. We demonstrate that MINAR1 physically interacts with Notch2 and its binding to Notch2 increases its stability and function. MINAR1 is widely expressed in various tissues including the epithelial cells of the breast and endothelial cells of blood vessels. MINAR1 plays a negative role in angiogenesis as it inhibits angiogenesis in cell culture and in mouse matrigel plug and zebrafish angiogenesis models. Furthermore, while MINAR1 is highly expressed in the normal human breast, its expression is significantly downregulated in advanced human breast cancer and its re-expression in breast cancer cells inhibited tumor growth. Our study demonstrates that MINAR1 is an IDP that negatively regulates angiogenesis and growth of breast cancer cells.

Expression of membrane progestin receptors (mPRs) in the bovine corpus luteum during the estrous cycle and first trimester of pregnancy

Progesterone (P4) affects luteal cell function through nuclear P4 receptors and via nongenomic mechanisms, presumably involving membrane P4 receptors. There are 2 types of these receptors: progesterone receptor membrane component (PGRMC) and membrane progestin receptor (mPR), including mPR alpha (mPRα), beta (mPRβ), and gamma (mPRγ), which belong to the progestin and adipoQ receptor family (PAQR 7, 8, and 5, respectively). The aim of this study was to evaluate mRNA expression, protein expression, and localization of mPRα, mPRβ, and mPRγ in the bovine corpus luteum (CL) on days 2–5, 6–10, 11–16, and 17–20 of the estrous cycle as well as on weeks 3–5, 6–8, and 9–12 of pregnancy (n = 5/each period). The highest mPRα mRNA expression was found on days 11–16 (P < 0.05) and 17–20 (P < 0.001) of the estrous cycle compared with other stages of the estrous cycle and pregnancy. The mPRβ mRNA level was highest (P < 0.01) on days 11–20 of the estrous cycle and in all stages of pregnancy. mPRγ mRNA expression was highest (P < 0.001) on days 17–20 of the estrous cycle and also during weeks 9–12 of pregnancy compared with the other stages of the estrous cycle and pregnancy. Only the mPRα protein was changed during the estrous cycle; there were no significant differences in protein expression of mPRβ and mPRγ during the estrous cycle and pregnancy. Immunostaining for the mPRα, mPRβ, and mPRγ proteins was detectable in the CL sections at all stages of the estrous cycle and pregnancy. Strong positive staining was observed in small luteal cells; this reaction was less evident in large luteal cells. All proteins were also localized in endothelial cells of blood vessels. The obtained data indicate variable expression of mPRα, mPRβ, and mPRγ in bovine CL during the estrous cycle and first trimester of pregnancy and suggest that P4 may be involved in the regulation of CL function via these membrane receptors during both the estrous cycle and pregnancy.

A case of Angiolymphoid hyperplasia with eosinophilia in proximal ascending colon mimicking colon carcinoma

Angiolymphoid hyperplasia with eosinophilia (ALHE) / Epithelioid hemangioma (EH) is a rare lesion commonly located in skin but arising in colon even rarer. It clinically follows a benign course of uncertain pathogenesis characterized histologically by plenty of proliferation of histiocytoid endothelial cells of blood vessels and infiltration by dense eosinophil, lymphocytes and plasma cells. The lesion may recur after excision but there is no report of metastasis. A case of sixty-four years male with severe pain in right iliac fossa with bloody stool had CT scan and noticed ulceration with bleeding sites on colonoscopy. Histopathological examination showed characteristic features of ALHE /EH in common location like skin. The lesion very often mimic as bleeding colonic carcinoma which necessitate colectomy. This is a rare case of ALHE /EH in proximal ascending colon.Bangladesh Journal of Medical Science Vol.17(1) 2018 p.158-160

Striated muscle gene therapy for the treatment of lipoprotein lipase deficiency.

Excessive circulating triglycerides due to reduction or loss of lipoprotein lipase activity contribute to hypertriglyceridemia and increased risk for pancreatitis. The only gene therapy treatment for lipoprotein lipase deficiency decreases pancreatitis but minimally reduces hypertriglyceridemia. Synthesized in multiple tissues including striated muscle and adipose tissue, lipoprotein lipase is trafficked to blood vessel endothelial cells where it is anchored at the plasma membrane and hydrolyzes triglycerides into free fatty acids. We conditionally knocked out lipoprotein lipase in differentiated striated muscle tissue lowering striated muscle lipoprotein lipase activity causing hypertriglyceridemia. We then crossed lipoprotein lipase striated muscle knockout mice with mice possessing a conditional avian retroviral receptor gene and injected mice with either a human lipoprotein lipase retrovirus or an mCherry control retrovirus. Post-heparin plasma lipoprotein lipase activity increased for three weeks following human lipoprotein lipase retroviral infection compared to mCherry infected mice. Human lipoprotein lipase infected mice had significantly lower blood triglycerides compared to mCherry controls and were comparable to wild-type blood triglyceride levels. Thus, targeted delivery of human lipoprotein lipase into striated muscle tissue identifies a potential therapeutic target for lipoprotein lipase deficiency.