The effects of topically applied polyNIPAM-based nanogels and their monomers on skin cyclooxygenase expression,ex vivo

Stimulus-responsive nanogels have potential as carriers for drugs targeting the skin. It is important to estimate the biocompatibility of such materials with the skin since they are directly in contact upon application and may induce irritation or inflammation. In the current work, blank (drug-free) polyN-isopropylacrylamide (polyNIPAM), poly(NIPAM copolymerized butyl acrylate) [poly(NIPAM-co-BA)], and poly(NIPAM copolymerized with 5% w/v acrylic acid) [poly(NIPAM-co-AAc)(5%)] nanogels were dosed onto freshly excised full-thickness porcine ear skin and the effects on the expression of cyclooxygenase-2 (COX-2) determined ex vivo by Western blotting. Modulated COX-2 expression was indicative that the material had penetrated the skin and keratinocytes of the viable epidermis. The poly(NIPAM-co-BA) nanogel was found to exert a proinflammatory response when applied topically, as reflected by 67% higher COX-2 expression relative to the control treatment (p = 0.0035). The data obtained for the poly(NIPAM-co-AAc)(5%) nanogel, on the other hand, indicated no significant modulation in the expression of COX-2 (p = 0.1578), suggesting the particles are compatible with skin. This was even the case in the presence of co-administered aqueous citric acid solution. Overall the data support the use of the multi-responsive poly(NIPAM-co-AAc)(5%) nanogel for triggered or controlled topical drug delivery applications.     

Topical photodynamic therapy using transfersomal aluminum phthalocyanine tetrasulfonate: in vitro and in vivo study

The efficacy of transfersomes (flexible liposomes) as a novel technique for topical delivery of the hydrophilic tetra-anionic photodynamic sensitizer aluminum (III) phthalocyanine tetrasulfonate (AlPcS4) was investigated, on mammalian fibroblasts and on Balb/c mice dorsal skin. AlPcS4 was loaded in transfersomes composed of phosphatidylcholine/sodium deoxycholate (5:1, 10:1, and 15:1?w/w, ratios), resulting in 110-, 160-, and 200-nm mean size vesicles with encapsulation efficiencies of 16, 25, and 30 %, respectively. In vitro studies on baby hamster kidney-21 fibroblasts revealed twofold enhancement of the photocytotoxicity of AlPcS4 loaded in transfersomes (Trans-AlPcS4), compared to free AlPcS4 dissolved in culture medium. The photocytotoxicity of Trans-AlPcS4 was less dependent on the incubation time with cells, compared to free AlPcS4. Topical application on the dorsal skin of Balb/c mice revealed that both free AlPcS4 and Trans-AlPcS4 exhibited evident photosensitization towards mice skin, but acquiring different regions of skin.     

Retrograde access via the popliteal artery to facilitate the re‐entry technique for recalcitrant superficial femoral artery Chronic total occlusions

Subintimal recanalization is beneficial in selected patients with peripheral chronic total occlusions (CTO). However, in complex cases, re‐entry into the true arterial lumen may prove to be unsuccessful with a conventional guidewire or a re‐entry catheter when using standard femoral artery access. Our case series describes these technical dilemmas along with strategies that can be utilized to overcome these challenges. © 2011 Wiley‐Liss, Inc.     

Tricuspid Regurgitation Following Implantation of a Pacemaker/Cardioverter-Defibrillator

Chronic symptomatic ischemic heart failure remains a major cause of morbidity and mortality in the adult. Recently, the utility of coronary revascularization in early management of patients with stable ischemic heart failure has come into question by several randomized clinical trials. Some of these studies have also challenged the notion that determination of the predominant state of the dysfunctional left ventricular myocardium (viable or scarred) may facilitate identification of patients who would benefit the most from revascularization. These prospective, randomized, multi-center trials have also exposed many of the practical impediments to conducting an ideal clinical investigation particularly in the context of increasingly recognized need for goal-directed and personalized approaches to management of ischemic heart disease. This review summarizes the present evidence for an ischemia-guided approach to evaluation and treatment of chronic ischemic heart disease with left ventricular systolic dysfunction.     

Lysine11-Linked Polyubiquitination of the AnkB F-Box Effector of Legionella pneumophila

The fate of the polyubiquitinated protein is determined by the lysine linkages involved in the polymerization of the ubiquitin monomers, which has seven lysine residues (K⁶, K¹¹, K²⁷, K²⁹, K³³, K⁴⁸, and K⁶³). The translocated AnkB effector of the intravacuolar pathogen Legionella pneumophila is a bona fide F-box protein, which is localized to the cytosolic side of the Legionella-containing vacuole (LCV) and is essential for intravacuolar proliferation within macrophages and amoebae. The F-box domain of AnkB interacts with the host SCF1 E3 ubiquitin ligase that triggers the decoration of the LCV with K⁴⁸-linked polyubiquitinated proteins that are targeted for proteasomal degradation. Here we report that AnkB becomes rapidly polyubiquitinated within the host cell, and this modification is independent of the F-box domain of AnkB, indicating host-mediated polyubiquitination. We show that the AnkB effector interacts specifically with the host E3 ubiquitin ligase Trim21. Mass spectrometry analyses have shown that AnkB is modified by K¹¹-linked polyubiquitination, which has no effect on its stability. This work shows the first example of K¹¹-linked polyubiquitination of a bacterial effector and its interaction with the host Trim21 ubiquitin ligase.     

Intestinal microbiota and its association with colon cancer and red/processed meat consumption

The human colon harbors a high number of microorganisms that were reported to play a crucial role in colorectal carcinogenesis. In the recent decade, molecular detection and metabolomic techniques have expanded our knowledge on the role of specific microbial species in promoting tumorigenesis. In this study, we reviewed the association between microbial dysbiosis and colorectal carcinoma (CRC). Various microbial species and their association with colorectal tumorigenesis and red/processed meat consumption have been reviewed. The literature demonstrated a significant abundance of Fusobacterium nucleatum, Streptococcus bovis/gallolyticus, Escherichia coli, and Bacteroides fragilis in patients with adenoma or adenocarcinoma compared to healthy individuals. The mechanisms in which each organism was postulated to promote colon carcinogenesis were collated and summarized in this review. These include the microorganisms' ability to adhere to colon cells; modulate the inhibition of tumor suppressor genes, the activations of oncogenes, and genotoxicity; and activate downstream targets responsible for angiogenesis. The role of these microorganisms in conjugation with meat components including N‐nitroso compounds, heterocyclic amines, and heme was also evident in multiple studies. The outcome of this review supports the role of red meat consumption in modulating CRC progression and the possibility of gut microbiome influencing the relationship between CRC and diet. The study also demonstrates that microbiota analysis could potentially complement existing screening methods when detecting colonic lesions.     

Application of artificial intelligence using a novel EUS-based convolutional neural network model to identify and distinguish benign and malignant hepatic masses

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