Alginate Formulations: Current Developments in the Race for Hydrogel-Based Cardiac Regeneration

Cardiovascular diseases, including myocardial infarction (MI), represent the main worldwide cause of mortality and morbidity. In this scenario, to contrast the irreversible damages following MI, cardiac regeneration has emerged as a novel and promising solution for in situ cellular regeneration, preserving cell behavior and tissue cytoarchitecture. Among the huge variety of natural, synthetic, and hybrid compounds used for tissue regeneration, alginate emerged as a good candidate for cellular preservation and delivery, becoming one of the first biomaterial tested in pre-clinical research and clinical trials concerning cardiovascular diseases. Although promising results have been obtained, recellularization and revascularization of the infarcted area present still major limitations. Therefore, the demand is rising for alginate functionalization and its combination with molecules, factors, and drugs capable to boost the regenerative potential of the cardiac tissue. The focus of this review is to elucidate the promising properties of alginate and to highlight its benefits in clinical trials in relation to cardiac regeneration. The definition of hydrogels, the alginate characteristics, and recent biomedical applications are herewith described. Afterward, the review examines in depth the ongoing developments to refine the material relevance in cardiac recovery and regeneration after MI and presents current clinical trials based on alginate

Identificação do gene phlD e análise da diversidade genética em isolados de Pseudomonas spp. pertencentes ao grupo fluorescente.

RESUMO – Bactérias do gênero Pseudomonas spp. pertencentes ao grupo fluorescente têm sido mencionadas como eficazes no controle de patógenos que atacam o sistema radicular de plantas. Desse modo, este trabalho se propôs a identificar isolados de Pseudomonas spp. fluorescentes sintetizadores de 2,4-diacetilfloroglucinol (2,4- DAPG), um antibiótico que apresenta atividade contra diversos patógenos radiculares de plantas, além de avaliar a diversidade genética desse gênero de bactérias utilizando a técnica de PCR-RFLP 16S RNAr. Pela técnica de PCR foi amplificado um fragmento do gene phlD, envolvido na síntese do 2,4-DAPG. Para o PCR-RFLP, o gene ribossomal 16S foi amplificado e o produto do PCR foi digerido com a enzima de restrição AluI. De um total de 1.274 isolados analisados, seis apresentaram o gene phlD, revelando que a incidência de Pseudomonas spp. produtoras de 2,4-DAPG é baixa nos solos do Paraná. A análise da diversidade genética, realizada em 50 isolados pela comparação dos padrões de restrição do gene 16S RNAr, revelou que bactérias isoladas de diferentes culturas vegetais apresentam elevada diversidade genética, sendo identificados 11 genótipos distintos

Reasons why HIV-positive women do not want to have a child: the questionnaire-based DIDI study

Given that the majority of HIV‐positive women are of reproductive age, it is necessary to understand the interaction between HIV and family planning, especially as antiretroviral medications allow to live longer, healthier lives. Aim of this analysis form the DIDI study was to assess prevalence of motherhood desire in current years and to identify variables associated pregnancy decision‐making in HIV‐infected women. DIDI is an Italian, 16‐center, questionnaire‐based survey performed in 585 HIV‐positive women between Nov. 2010 and Feb. 2011. The items covered in the self‐administered questionnaire included: socio‐demographic characteristics, sexual and gynecological health, motherhood desire, strategies adopted to become pregnant, reasons for not wanting a child, partnership, HIV disclosure, physical and mental health, ART adherence, drug use. For the present analysis only women aged<45 years and engaged in a partnership were included. Absence of motherhood desire was defined by a negative answer at the question whether the women at present would like to have a child. 178 women were included: mean age 39 (IQR, 33–42), HIV transmission heterosexual 75%, IVDU 11%, heterosexual/IVDU 2.5%, not known 7.5%; mean CD4 and HIV‐RNA were 552/mmc (+252) and 3.85 c/ml (+4.7), respectively. Absence of motherhood desire was found in 61% of women; 50% of women declared that HIV negatively affected motherhood desire, and 22% declared a decrease in desire after start of ART. The probability of vertical transmission was estimated higher than 50% by 19% of women, even when adopting all preventive measures. Not wanting a child was associated with: fear of vertical transmission (p<0.001), fear of not being able to raise the child (p<0.001), decline in motherhood desire after HIV (p=0.007), unstable partnership (p=0.02). At multivariable analysis, variables found to be significantly associated with negative pregnancy decision‐making were: fear of vertical transmission (AOR 3.75; 95%CI 1.18–11.89), economic restrictions (AOR 0.28; 95% CI 0.10–0.76 In conclusion, absent motherhood desire in HIV‐positive women with child‐bearing potential is frequent and essential information on vertical HIV transmission is lacking. HIV‐positive women of childbearing age may benefit from counseling interventions sensitive to factors that influence infected women's pregnancy decisions

Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma.

Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas

Catalytic processing in ruthenium-based polyoxometalate coacervate protocells

The development of programmable microscale materials with cell-like functions, dynamics and collective behaviour is an important milestone in systems chemistry, soft matter bioengineering and synthetic protobiology. Here, polymer/nucleotide coacervate micro-droplets are reconfigured into membrane-bounded polyoxometalate coacervate vesicles (PCVs) in the presence of a bio-inspired Ru-based polyoxometalate catalyst to produce synzyme protocells (Ru4PCVs) with catalase-like activity. We exploit the synthetic protocells for the implementation of multi-compartmentalized cell-like models capable of collective synzyme-mediated buoyancy, parallel catalytic processing in individual horseradish peroxidase-containing Ru4PCVs, and chemical signalling in distributed or encapsulated multi-catalytic protocell communities. Our results highlight a new type of catalytic micro-compartment with multi-functional activity and provide a step towards the development of protocell reaction networks. \ua9 2020, The Author(s)

Generation and characterization of three human induced pluripotent stem cell lines (EURACi007-A, EURACi008-A, EURACi009-A) from three different individuals of the same family with arrhythmogenic cardiomyopathy (ACM) carrying the plakophillin2 p.N346Lfs*12 mutation.

Abstract Arrhythmogenic Cardiomyopathy (ACM) is a genetically based cardiomyopathy associated with ventricular arrhythmias and fibro-fatty substitution of cardiac tissue. It is characterized by incomplete penetrance. We generated human iPSCs by episomal reprogramming of blood cells from three members of the same family: the proband, affected by ACM and carrying the heterozygous plakophillin2 p.N346Lfs*12 mutation, one asymptomatic carrier of the same mutation and one apparently healthy control. hiPSCs were characterized according to standard protocols including karyotyping, pluripotency marker expression and differentiation towards the three germ layers. These hiPSC lines can be used to study the mechanisms of ACM incomplete penetrance in vitro

Collagen Type IV Alpha 5 Chain in Bronchiolitis Obliterans Syndrome After Lung Transplant: The First Evidence

Introduction: Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometry pattern without parenchymal opacities. The protein signature of BOS lesions concerns extracellular matrix organization and aberrant basement membrane composition. In this pilot study, we investigated the presence of COL4A5 in the serum of patients with BOS. Methods: 41 patients who had undergone LTX were enrolled. Of these, 27 developed BOS and 14 (control group) were considered stable at the time of serum sampling. Of BOS patients, serum samples were analysed at the time of BOS diagnosis and before the clinical diagnosis (pre-BOS). COL4A5 levels were detected through the ELISA kit. Results: Serum concentrations of COL4A5 were higher in pre-BOS than in stable patients (40.5 ± 13.9 and 24.8 ± 11.4, respectively, p = 0.048). This protein is not influenced by comorbidities, such as acute rejection or infections, or by therapies. Survival analysis also reveals that a higher level of COL4A5 was also associated with less probability of survival. Our data showed a correlation between concentrations of COL4A5 and FEV1 at the time of diagnosis of BOS. Conclusion: Serum concentrations of COL4A5 can be considered a good prognostic marker due to their association with survival and correlation with functional parameters