Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells

Epigenetic regulation of gene expression is critical to phenotypic maintenance and transition of human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) is a long intergenic non-coding RNA that epigenetically represses gene expression via recruitment of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase. Elevated expression of HOTAIR promotes progression of breast cancer. In the current study we examined the expression and function of HOTAIR in MCF-7-TNR cells, a derivative of the luminal-like breast cancer cell line MCF-7 that acquired resistance to TNF-α-induced cell death. The expression of HOTAIR, markers of the luminal-like and basal-like subtypes, and growth were compared between MCF-7 and MCF-7-TNR cells. These variables were further assessed upon inhibition of HOTAIR, EZH2, p38 MAPK, and SRC kinase in MCF-7-TNR cells. When compared with MCF-7 cells, MCF-7-TNR cells exhibited an increase in the expression of HOTAIR, which correlated with characteristics of a luminal-like to basal-like transition as evidenced by dysregulated gene expression and accelerated growth. MCF-7-TNR cells exhibited reduced suppressive histone H3 lysine27 trimethylation on the HOTAIR promoter. Inhibition of HOTAIR and EZH2 attenuated the luminal-like to basal-like transition in terms of gene expression and growth in MCF-7-TNR cells. Inhibition of p38 and SRC diminished HOTAIR expression and the basal-like phenotype in MCF-7-TNR cells. HOTAIR was robustly expressed in the native basal-like breast cancer cells and inhibition of HOTAIR reduced the basal-like gene expression and growth. Our findings suggest HOTAIR-mediated regulation of gene expression and growth associated with the basal-like phenotype of breast cancer cells

Berbris aristata DC: Pharmacognostical Standardization and Phytochemical Studies of its Leaves

Berberis aristata DC. (Fam: Berberidaceae) commonly known as Daruharidra, Indian Barberry or tree turmeric. Leaves of this plant are traditionally used in the treatment of inflammation, wound healing, skin disease, menorrhagia, diarrhea, jaundice and infection of eyes etc. Micromorphology and physicochemical analysis of the leaves of B.aristata were performed as per WHO and Pharmacopoeial methods. Leaves (4.9cm × 1.8cm) are deep green on dorsal and light green on ventral side. Leaves are in tufts of 5 to 8, phyllotaxy verticillate, simple spiny, lanceolate, toothed, leathery, sessile, acuminate apex and reticulate pinnate venation. Microscopic evaluation of leaves showed biconvex midrib and thick lamina. The epidermal layers of the midrib are thick with small, less conspicuous cells and thick cuticle. The vascular system consists of three large vascular bundles; the median one is small than the two lateral bundles; the bundles are collateral and wedge shaped.  Lamina is made of epidermal layer on the adaxial side with spindle shaped thick walled cells and papillate cuticle. The abaxial epidermis has squarish or rectangular epidermal cells with prominent spiny cuticular outgrowths. Powder microscopy showed the presence of cuticular papillae, anomocytic stomata and spiny outgrowth. Preliminary phytochemical screening of appropriate solvent extracts showed the presence of alkaloids, sterols, tannins, proteins and amino acids, flavonoids, terpenoids, saponin, carbohydrates and absence of glycosides and volatile and fixed oil. Microscopic analysis and other parameters were informative and provide valuable information in the identification, standardization of B.aristata leaves. Keywords: Berberis aristata, Berberidaceae, leaf, Microscopical evaluation

Optimizing extraction of cellulose and synthesizing pharmaceutical grade carboxymethyl sago cellulose from Malaysian sago pulp

Sago biomass is an agro-industrial waste produced in large quantities, mainly in the Asia-Pacific region and in particular South-East Asia. This work focuses on using sago biomass to obtain cellulose as the raw material, through chemical processing using acid hydrolysis, alkaline extraction, chlorination and bleaching, finally converting the material to pharmaceutical grade carboxymethyl sago cellulose (CMSC) by carboxymethylation. The cellulose was evaluated using Thermogravimetric Analysis (TGA), Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC) and Field Emission Scanning Electronic Microscopy (FESEM). The extracted cellulose was analyzed for cellulose composition, and subsequently modified to CMSC with a degree of substitution (DS) 0.6 by typical carboxymethylation reactions. X-ray diffraction analysis indicated that the crystallinity of the sago cellulose was reduced after carboxymethylation. FTIR and NMR studies indicate that the hydroxyl groups of the cellulose fibers were etherified through carboxymethylation to produce CMSC. Further characterization of the cellulose and CMSC were performed using FESEM and DSC. The purity of CMSC was analyzed according to the American Society for Testing and Materials (ASTM) International standards. In this case, acid and alkaline treatments coupled with high-pressure defibrillation were found to be effective in depolymerization and defibrillation of the cellulose fibers. The synthesized CMSC also shows no toxicity in the cell line studies and could be exploited as a pharmaceutical excipient

Pharmacognostical Standardization and Phytochemical Studies on the leaves of Solanum torvum Sw

A genus of plant belongs to the family Solanaceae well distributed in India more than 26 species which are found naturalised in India. Solanum torvum Sw. is a medium sized flowering plant in the Solanaceae family that is found in India, Malaysia. Transverse section of lamina showed the adaxial part has thick, short hump; the midrib and the adaxial hump have thin, angular epidermal cells. The upper part of adaxial hump has a few layers sclerenchyma cells. The inner layer of the adaxial midrib also has few layers of thick walled cells. The ground tissue consists of wide circular thin walled parenchyma cells with narrow inter cellular spaces. The vascular system of the midrib showed bi-collateral structure. Non glandular, profusely branched, thick walled, lignified epidermal trichome occurs as both on the veins and lamina. Physico-chemical standards such as Foreign Matter, Total Ash, Water Soluble Ash, Sulphated Ash, Loss on Drying, Water Soluble Extractive, Alcohol Soluble Extractive and Crude Fiber Content in percentage were estimated. Preliminary phytochemical screening of appropriate solvent extracts showed the presence of Alkaloids, Amino Acids, Carbohydrates, Cellulose, Lignin, Fats & Fixed Oils, Flavonoids, Glycosides, Tannins, Proteins, Starch, Steroids and Triterpenoids and absence of Volatile Oil, Mucilage and Pectin. Microscopic analysis and other parameters were informative and provide valuable information in the identification, standardization of Solanum torvum leaves. Keywords: Solanum torvum, Solanaceae, leaf, Microscopical evaluation

Dedicated plug based closure for large bore access -The MARVEL prospective registry

Objectives To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers. Background The MANTA is a novel plug-based device for large bore arteriotomy closure. Methods We included all eligible patients who underwent transfemoral large bore percutaneous procedures. Exclusion criteria were per operator's discretion and included severe calcification or marked tortuosity of the access vessel, presence of marked obesity/cachexia or a systolic blood pressure above 180 mmHg. The primary performance endpoint was time to hemostasis. Primary and secondary safety endpoints were major and minor access site related vascular complications up to 30 days, respectively. Vascular complications were adjudicated by an independent clinical event committee according to VARC-2 criteria. We performed multivariable logistic regression to estimate the effect of baseline and procedural characteristics on any and major vascular complications. Results Between February 2018 and July 2019 500 patients were enrolled undergoing Transcatheter aortic valve replacement (TAVR, N = 496), Balloon aortic valvuloplasty (BAV, N = 2), Mechanical circulatory support (MCS, N = 1) or Endovascular aneurysm repair (EVAR, N = 1). Mean age was 80.8 +/- 6.6 years with a median STS-score of 2.7 [IQR 2.0-4.3] %. MANTA access site complications were major in 20 (4%) and minor in 28 patients (5.6%). Median time to hemostasis was 50 [IQR 20-120] sec. Severe femoral artery calcification, scar presence in groin, longer procedure duration, female gender and history of hypertension were independent predictors for vascular complications. Conclusion In this study, MANTA appeared to be a safe and effective device for large bore access closure under real-world conditions.Peer reviewe

Induction of Stable Drug Resistance in Human Breast Cancer Cells Using a Combinatorial Zinc Finger Transcription Factor Library

Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust tool for inducing and understanding various functional components of the cancer phenotype. Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to fulvestrant, a clinically important anti-endocrine therapeutic agent. From a diverse collection of nearly 400,000 different ZF-TFs, we isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor-positive breast cancer cell lines. Comparative gene expression profile analysis of the six different ZF-TF-transduced breast cancer cell lines revealed five distinct clusters of differentially expressed genes. One cluster was shared among all 6 ZF-TF-transduced cell lines and therefore constituted a common fulvestrant-resistant gene expression signature. Pathway enrichment-analysis of this common fulvestrant resistant signature also revealed significant overlap with gene sets associated with an estrogen receptor-negative-like state and with gene sets associated with drug resistance to different classes of breast cancer anti-endocrine therapeutic agents. Enrichment-analysis of the four remaining unique gene clusters revealed overlap with myb-regulated genes. Finally, we also demonstrated that the common fulvestrant-resistant signature is associated with poor prognosis by interrogating five independent, publicly available human breast cancer gene expression datasets. Our results demonstrate that artificial ZF-TF libraries can be used successfully to induce stable drug-resistance in human cancer cell lines and to identify a gene expression signature that is associated with a clinically relevant drug-resistance phenotype

Exploring the Darkverse:A Multi-Perspective Analysis of the Negative Societal Impacts of the Metaverse

The Metaverse has the potential to form the next pervasive computing archetype that can transform many aspects of work and life at a societal level. Despite the many forecasted benefits from the metaverse, its negative outcomes have remained relatively unexplored with the majority of views grounded on logical thoughts derived from prior data points linked with similar technologies, somewhat lacking academic and expert perspective. This study responds to the dark side perspectives through informed and multifaceted narratives provided by invited leading academics and experts from diverse disciplinary backgrounds. The metaverse dark side perspectives covered include: technological and consumer vulnerability, privacy, and diminished reality, human–computer interface, identity theft, invasive advertising, misinformation, propaganda, phishing, financial crimes, terrorist activities, abuse, pornography, social inclusion, mental health, sexual harassment and metaverse-triggered unintended consequences. The paper concludes with a synthesis of common themes, formulating propositions, and presenting implications for practice and policy.</p

Differences sustained between diffuse and limited forms of juvenile systemic sclerosis in expanded international cohort. www.juvenile-scleroderma.com

OBJECTIVES: To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (jSSc) patients in the international Juvenile SSc Inception Cohort (jSScC), compare these characteristics between the classically defined diffuse (dcjSSc) and limited cutaneous (lcjSSc) subtypes, and among those with overlap features. METHODS: A cross-sectional study was performed using baseline visit data. Demographic, organ system evaluation, treatment, and patient and physician reported outcomes were extracted and summary statistics applied. Comparisons between dcjSSc and lcSSc subtypes and patients with and without overlap features were performed using Chi-square and Mann Whitney U-tests. RESULTS: At data extraction 150 jSSc patients were enrolled across 42 centers, 83% were Caucasian, 80% female, dcjSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between dcjSSc and lcjSSc regarding the modified Rodnan Skin Score, presence of Gottron's papules, digital tip ulceration, 6 Minute walk test, composite pulmonary and cardiac involvement. All more frequent in dcSSc except for cardiac involvement. DcjSSc patients had significantly worse scores for physician rated disease activity and damage. A significantly higher occurrence of Gottron's papules, musculoskeletal involvement and composite pulmonary involvement, and significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. CONCLUSION: Results from a large international jSSc cohort demonstrate significant differences between dcjSSc and lcjSSc patients including more globally severe disease and increased frequency of ILD in dcjSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease

Distribution of Blastocystis subtypes isolated from humans from an urban community in Rio de Janeiro, Brazil

Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ginecologia e Obstetrícia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina, Departamento de Medicina Preventiva. Rio de Janeiro, RJ, brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Hospital Universitário Antonio Pedro. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.Blastocystis is a cosmopolitan protist parasite found in the human gastrointestinal tract and is highly prevalent in developing countries. Recent molecular studies have revealed extensive genetic diversity, which has been classified into different subtypes (STs) based on sequence analysis of small subunit ribosomal RNA gene. Blastocystis is one of the most common fecal parasites in Brazil, but the diversity of subtypes remains unknown in the country. This study aimed to determine the distribution of Blastocystis STs in an urban community in Duque de Caxias, Rio de Janeiro, Brazil