The Long Non-Coding RNA Gene AC027288.3 Plays a Role in Human Endometrial Stromal Fibroblast Decidualization.

During the secretory phase of the menstrual cycle, endometrial fibroblast cells begin to change into large epithelial-like cells called decidual cells in a process called decidualization. This differentiation continues more broadly in the endometrium and forms the decidual tissue during early pregnancy. The cells undergoing decidualization as well as the resulting decidual cells, support successful implantation and placentation during early pregnancy. This study was carried out to identify new potentially important long non-coding RNA (lncRNA) genes that may play a role in human endometrial stromal fibroblast cells (hESF) undergoing decidualization in vitro, and several were found. The expression of nine was further characterized. One of these, AC027288.3, showed a dramatic increase in the expression of hESF cells undergoing decidualization. When AC027288.3 expression was targeted, the ability of the cells to undergo decidualization as determined by the expression of decidualization marker protein-coding genes was significantly altered. The most affected markers of decidualization whose expression was significantly reduced were FOXO1, FZD4, and INHBA. Therefore, AC027288.3 may be a major upstream regulator of the WNT-FOXO1 pathway and activin-SMAD3 pathways previously shown as critical for hESF decidualization. Finally, we explored possible regulators of AC027288.3 expression during human ESF decidualization. Expression was regulated by cAMP and progesterone. Our results suggest that AC027288.3 plays a role in hESF decidualization and identifies several other lncRNA genes that may also play a role.

ATOH8 Expression Is Regulated by BMP2 and Plays a Key Role in Human Endometrial Stromal Cell Decidualization.

During the secretory phase of the menstrual cycle, elongated fibroblast-like mesenchymal cells in the uterine endometrium begin to transdifferentiate into polygonal epithelioid-like (decidual) cells. This decidualization process continues more broadly during early pregnancy, and the resulting decidual tissue supports successful embryo implantation and placental development. This study was carried out to determine if atonal basic helix-loop-helix transcription factor 8 (ATOH8) plays a role in human endometrial stromal fibroblast (ESF) decidualization. ATOH8 messenger RNA and protein expression levels significantly increased in human ESF cells undergoing in vitro decidualization, with the protein primarily localized to the nucleus. When ATOH8 expression was silenced, the ability of the cells to undergo decidualization was significantly diminished. Overexpression of ATOH8 enhanced the expression of many decidualization markers. Silencing the expression of ATOH8 reduced the expression of FZD4, FOXO1, and several known FOXO1-downstream targets during human ESF cell decidualization. Therefore, ATOH8 may be a major upstream regulator of the WNT/FZD-FOXO1 pathway, previously shown to be critical for human endometrial decidualization. Finally, we explored possible regulators of ATOH8 expression during human ESF decidualization. BMP2 significantly enhanced ATOH8 expression when cells were stimulated to undergo decidualization, while an ALK2/3 inhibitor reduced ATOH8 expression. Finally, although the steroids progesterone plus estradiol did not affect ATOH8 expression, the addition of cyclic adenosine monophosphate (cAMP) analogue alone represented the major effect of ATOH8 expression when cells were stimulated to undergo decidualization. Our results suggest that ATOH8 plays a crucial role in human ESF decidualization and that BMP2 plus cAMP are major regulators of ATOH8 expression.

Cyclic Fevers in Adult Diagnosed As Hyperimmunoglobulin D Syndrome.

Hyper immunoglobulin D Syndrome (HIDS) is a rare autosomal recessive disease often presents during infancy. The disease is caused by an abnormal gene that codes for mevalonate kinase (MVK). This results in recurrent fever episodes and gastrointestinal discomfort (including diarrhea, joint pain, and oral sores). High fever is the most common symptom, occurring every few weeks to months. Patients may also have other findings, including lymphadenopathy and arthralgia. In this report, we discuss a rare diagnosis of HIDS is an adult and discuss our case in the context of existing literature. Given the nonspecific symptoms and the fact that it is often diagnosed in childhood, HIDS can be a challenging but essential diagnosis in adults with persistent, cyclical fevers.

Scleroderma associated with renal cell carcinoma: A case report and literature review.

Introduction: Systemic sclerosis (aka scleroderma) is an autoimmune disease with no known definitive etiology, but genetic, infectious, and non-infectious exposures have been associated with its occurrence. Previous studies have shown that systemic sclerosis can be a paraneoplastic phenomenon and may be associated with increased risk of malignancy, most commonly lung, skin, and breast cancers. The association of renal cell carcinoma with systemic sclerosis is rare. Case Description: Here, we present a case of a 75-year-old male patient with a rapidly progressive scleroderma despite the initial treatment with methotrexate and prednisone 5 mg daily. Shortly after the diagnosis of scleroderma, the patient was found to have a renal mass. The patient underwent a right partial nephrectomy revealing papillary renal cell carcinoma. The surgical margin was negative indicating complete removal of the cancer. The patient, later, developed scleroderma renal crisis and progressed to end-stage renal disease despite treatment with captopril, mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin. Conclusions: The purpose of this case report and literature review is to highlight that diffuse scleroderma can potentially be paraneoplastic from a renal cell carcinoma and to add more data to the literature given there are only a handful of reported cases. Our patient is unique in the sense that he was discovered to have renal cell carcinoma shortly after being diagnosed with scleroderma suggesting a paraneoplastic etiology yet continued to worsen despite full resection of the renal cell carcinoma. This is in contrast to the other reported cases of renal cell carcinoma associated scleroderma where scleroderma worsened around the time of the diagnosis of renal cell carcinoma and improved after nephrectomy. There also are case reports of the patients with renal cell carcinoma associated scleroderma where the patient had scleroderma for several years before the diagnosis of renal cell carcinoma, which raises the question, if scleroderma could also represent a risk factor for developing renal cell carcinoma.

Chemical composition, antioxidant and antibacterial activities of essential oil and methanol extract of Artemisia vulgaris and Gaultheria fragrantissima collected from Nepal.

OBJECTIVE: To identify the chemical constituents and biological activities of essential oil and crude methanol extract of Artemisia vulgaris (A. vulgaris) and Gaultheria fragrantissima (G. fragrantissima). METHODS: Phytochemical screening, total phenolic and flavonoid content, antibacterial activities, anti-oxidant assay of the crude extract were carried out to identify the biological activities and phytonutrients present in the extract. Furthermore, the chemical constituents present in the essential oil and crude methanol extract were analyzed using gas chromatography mass spectroscopy and high performance liquid chromatography (HPLC) analysis. RESULTS: Gas chromatography mass spectroscopy analysis of essential oil from the aerial part of A. vulgaris revealed 24 different compounds in it. Sabinene (11.29%), ß-thujone (19.19%), chrysanthenone (4.48%), camphor (11.89%), borneol (4.44%) and germacrene D (8.42%) were the major compounds. Similarly, leaves of G. fragrantissima contained methyl salicylate (95%) and asarone (4.64%). Furthermore, methanol extract of leaves of A. vulgaris and G. fragrantissima were found rich in the total flavonoids and phenolic content. HPLC analysis of the methanol extract of leaves A. vulgaris revealed the presence of morin and luteolin, whereas rutin was found as a major flavonoids compound in the leaves of G. fragrantissima. Further, methanol extract of the A. vulgaris and G. fragrantissima showed the highest antioxidant and antibacterial properties compared to the essential oil. CONCLUSIONS: The HPLC analysis of the methanol extract of A. vulgaris shows the presence of luteolin and morin, whereas G. fragrantissima reveals the presence of rutin and a glycosylated flavonoids. Results reveal that A. vulgaris oil is the rich source of monoterpene and sesquiterpene compounds. Furthermore, A. vulgaris and G. fragrantissima are the rich source of the phenolic and flavonoids compounds and show good antioxidant and antibacterial activity.

Enzyme-mediated formulation of stable elliptical silver nanoparticles tested against clinical pathogens and MDR bacteria and development of antimicrobial surgical thread.

BACKGROUND: Silver nanoparticles (AgNPs) are believed to be emerging tool against various infectious diseases including multi-drug resistant (MDR) bacteria. In the present study, in vitro synthesis of AgNPs was optimized using 1:50 ratio of macerozyme (25 µg/µl) and 1 mM AgNO3 incubated at 80 °C for 8 h. AgNPs were characterized by UV-Visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy (TEM) and X-ray diffraction (XRD). RESULTS: Characterization studies suggest the synthesis of elliptical, stable and crystalline AgNPs with an average size of 38.26 ± 0.4 nm calculated using TEM. The XRD pattern revealed the face-centered-cubic (fcc) form of metallic silver. Good shape integrity and dispersion of AgNPs after 1 year of incubation confirmed their stability. AgNPs were exibited the antimicrobial property against ten pathogenic bacteria, three molds and one yeast. The AgNPs also revealed remarkable antimicrobial activity against three MDR strains i.e. Extended spectrum beta-lactamase positive Escherichia coli, Staphylococcus aureus (MRSA) and Teicoplanin resistant Streptococcus Pneumoniae. The AgNPs coated surgical threads (suture) were revealed the remarkble antibacterial activity against three MDR strains. This is the first report to synthesize antimicrobial elliptical AgNPs using enzymes. CONCLUSION: The results suggest the possibilities to develop the nanoparticles coated antimicrobial medical fabric to combat against MDR infection.