Label-free plasmonic immunosensor for cortisol detection in a D-shaped optical fiber.

Measuring cortisol levels as a stress biomarker is essential in many medical conditions associated with a high risk of metabolic syndromes such as anxiety and cardiovascular diseases, among others. One technology that has a growing interest in recent years is fiber optic biosensors that enable ultrasensitive cortisol detection. Such interest is allied with progress being achieved in basic interrogation, accuracy improvements, and novel applications. The development of improved cortisol monitoring, with a simplified manufacturing process, high reproducibility, and low cost, are challenges that these sensing mechanisms still face, and for which solutions are still needed. In this paper, a comprehensive characterization of a D-shaped fiber optic immunosensor for cortisol detection based on surface plasmon resonance (SPR) enabled by gold coating is reported. Specifically, the sensor instrumentation and fabrication processes are discussed in detail, and a simulation with its complete mathematical formalism is also presented. Moreover, experimental cortisol detection tests were performed for a detection range of 0.01 to 100 ng/mL, attaining a logarithmic sensitivity of 0.65 ± 0.02 nm/log(ng/mL) with a limit of detection (LOD) of 1.46 ng/mL. Additionally, an investigation of signal processing is also discussed, with the main issues addressed in order to highlight the best way to extract the sensing information from the spectra measured with a D-shaped sensor.

Macrophage interactions with collecting duct epithelial cells are capable of driving tubulointerstitial inflammation and fibrosis in immunoglobulin A nephropathy.

BACKGROUND: Tubulointerstitial fibrosis is a powerful predictor of future progression inimmunoglobulin A (IgA) nephropathy (IgAN). Proximal tubular epithelial cells (PTECs), in concert with infiltrating macrophages, are regarded as the agents provocateurs for driving this fibrotic process. However, evidence is now emerging for a contributory role of the distal nephron. The aim of this study was to examine the potential influence of macrophages on collecting duct epithelial cells (CDECs) and their combined role in the progression of IgAN. METHODS: CDECs were cultured with macrophage-conditioned media (MCM) generated from human monocyte cell lines U937 and THP-1 stimulated with or without 100 µg/mL galactose-deficient IgA1. CDECs were analysed for evidence of inflammation and fibrosis. RESULTS: Staining of IgAN biopsies for CD68+ macrophages revealed the presence of macrophages juxtaposed to collecting ducts and within their lumina. CDEC exposed to MCM from IgA1-stimulated THP-1 cells (THP-1-IgA-MCM) exhibited markedly increased expression of neutrophil-associated gelatinase (NGAL) and proinflammatory cytokinesinterleukin (IL)-1ß, tumour necrosis factor-α, IL-6 and IL-8 compared with MCM from non-IgA-stimulated THP-1 cells (THP-1-MCM). U937-IgA-MCM increased fibronectin levels and reduced E-cadherinmRNA expression. THP-1-IgA-MCM-derived exosomes induced similar increases in NGAL and cytokine expression while in cross-over experiments exosomes extracted from IL-1ß-exposed CDEC induced IL-1ß and IL-6 mRNA expression in both sets of macrophages. MiRnome analysis revealed that microRNA (miR)-146a, -155 and -200b exhibited a >2-fold increase in expression in CDEC treated with THP-1-IgA-MCM compared with THP-1-MCM. Enforced miR-146a suppression further enhanced NGAL expression, while ectopic miR-146a over-expression downregulated it. NGAL mRNA and miR-146a were upregulated in the biopsies of patients with progressive IgAN compared with non-progressive IgAN. CONCLUSIONS: Taken together, these data suggest that CDEC-macrophage interactions potentially contribute to the tubulointerstitial fibrosis characteristic of progressive IgAN.

Lovastatin production: From molecular basis to industrial process optimization.

Lovastatin, composed of secondary metabolites produced by filamentous fungi, is the most frequently used drug for hypercholesterolemia treatment due to the fact that lovastatin is a competitive inhibitor of HMG-CoA reductase. Moreover, recent studies have shown several important applications for lovastatin including antimicrobial agents and treatments for cancers and bone diseases. Studies regarding the lovastatin biosynthetic pathway have also demonstrated that lovastatin is synthesized from two-chain reactions using acetate and malonyl-CoA as a substrate. It is also known that there are two key enzymes involved in the biosynthetic pathway called polyketide synthases (PKS). Those are characterized as multifunctional enzymes and are encoded by specific genes organized in clusters on the fungal genome. Since it is a secondary metabolite, cultivation process optimization for lovastatin biosynthesis has included nitrogen limitation and non-fermentable carbon sources such as lactose and glycerol. Additionally, the influences of temperature, pH, agitation/aeration, and particle and inoculum size on lovastatin production have been also described. Although many reviews have been published covering different aspects of lovastatin production, this review brings, for the first time, complete information about the genetic basis for lovastatin production, detection and quantification, strain screening and cultivation process optimization. Moreover, this review covers all the information available from patent databases covering each protected aspect during lovastatin bio-production.

Adenoma pleomórfico em mucosa jugal: relato de caso / Pleomorphic adenoma on the buccal mucosa: a case report

O adenoma pleomórfico, que é uma neoplasia mista de glândula salivar, é uma morbidade relativamente comum. Apresenta prevalência dominante como neoplasia em glândula parótida, podendo acometer também glândulas salivares menores. É derivado de uma mistura de elementos ductais e mioepiteliais. O tumor geralmente é solitário e apresenta umcrescimento lento e indolor, como massa nodular única, independentedo sítio de origem. Quando intraoral é mais comum em palato duro e lábio superior, sendo relativamente incomum em mucosa jugal. Nesse trabalho, relata-se um caso clínico de adenoma pleomórfico em mucosa jugal, apresentando sete anos de evolução, com completa resolução após o tratamento cirúrgico conservador.

The pleomorphic adenoma, which is a mixed salivary gland neoplasm, is a relatively common disease. It has dominant prevalence such as neoplasm on parotid gland may also affect the minor salivary glands. It is derived from a mixture of ductal and myoepithelial elements. The tumor is usually solitary and presents a slow and pain less growth, being a single mass, independent of site of origin. When intraoral, it is more common onthe hard palate and upper lip. It is relatively uncommon on the buccal mucosa. In this paper, we report a case of pleomorphic adenoma in the buccal mucosa, with seven years of evolution, with complete resolution after conservatory surgical treatment.