Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1^−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2^−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.     

Replacing the Burden of the Gluten Free Diet: Then,Now, and the Future

Without a doubt, a majority of diseases are food-pattern-related. However, one disease stands out as an increasingly more common autoimmune-mediated enteropathy triggered by the ingestion of gluten. Celiac disease (CD) is an old disease, with changing clinical patterns, affecting any age, including infancy and adolescence, and becoming more frequent among the elderly. The gluten-free diet (GFD) has been the sole provider of clinical, serological, and histological improvement for patients with CD for more than seven decades. Nowadays, complete avoidance of dietary gluten is rarely possible because of the wide availability of wheat and other processed foods that contain even more gluten, to the detriment of gluten-free products. Undeniably, there is a definite need for replacing the burdensome GFD. An add-on therapy that could control the dietary transgressions and inadvertent gluten consumption that can possibly lead to overt CD should be considered while on GFD. Nevertheless, future drugs should be able to provide patients some freedom to self-manage CD and increase food independence, while actively reducing exposure and mucosal damage and alleviating GI symptoms. Numerous clinical trials assessing different molecules have already been performed with favorable outcomes, and hopefully they will soon be available for patient use.     

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.     

Intraoperative Tumor Detection Using Pafolacianine

Cancer is a leading cause of death worldwide, with increasing numbers of new cases each year. For the vast majority of cancer patients, surgery is the most effective procedure for the complete removal of the malignant tissue. However, relapse due to the incomplete resection of the tumor occurs very often, as the surgeon must rely primarily on visual and tactile feedback. Intraoperative near-infrared imaging with pafolacianine is a newly developed technology designed for cancer detection during surgery, which has been proven to show excellent results in terms of safety and efficacy. Therefore, pafolacianine was approved by the U.S. Food and Drug Administration (FDA) on 29 November 2021, as an additional approach that can be used to identify malignant lesions and to ensure the total resection of the tumors in ovarian cancer patients. Currently, various studies have demonstrated the positive effects of pafolacianine’s use in a wide variety of other malignancies, with promising results expected in further research. This review focuses on the applications of the FDA-approved pafolacianine for the accurate intraoperative detection of malignant tissues. The cancer-targeting fluorescent ligands can shift the paradigm of surgical oncology by enabling the visualization of cancer lesions that are difficult to detect by inspection or palpation. The enhanced detection and removal of hard-to-detect cancer tissues during surgery will lead to remarkable outcomes for cancer patients and society, specifically by decreasing the cancer relapse rate, increasing the life expectancy and quality of life, and decreasing future rates of hospitalization, interventions, and costs.     

Influence of pigment properties on UV‐curing efficiency

The curable formulations containing monomer‐diacrylate, photoinitiator‐p‐methoxybenzoyldiphenylphosphine oxide/benzyldimethylketal, additive reactive‐triethylamine, and inorganic thermoresistant pigments‐white, red, green, and blue were cured by UV exposure films. A series of experiments was carried out to investigate the relationship between the particle size distribution of the inorganic pigment and the colorimetric and mechanical properties of the UV acrylic curable coatings. Pendulum hardness and appearance of the films depend on the content and particle size distribution of the pigment. Optimal particle size distribution and pigment content were established to obtain the best films concerning their pendulum hardness and chromatic parameters. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 247–252, 2007     

Miscibility and properties of linear poly(l-lactide)/branched poly(l-lactide) copolyester blends

Polymer blends consisting of linear poly(l-lactide) (PLLA) and different proportions of dendritic PLLA-based copolyesters (hb-PLLA) characterized by different degrees of branching (DB) were obtained in melt. The solid-state properties of poly(l-lactide)s and their blends were investigated by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), atomic force microscopy (AFM) and stress-strain measurements. DSC and DMA methods proved miscibility of PLLA/hb-PLLA blends for the studied composition range. AFM indicated that no phase separation occurs in PLLA/hb-PLLA blends and that PLLA and hb-PLLA cocrystallize in one single lamellae type. The mechanical characteristics of PLLA/hb-PLLA blends deteriorated with an increase of the DB and with changing blend composition. Susceptibility of the blends to biodegradation was studied by measuring the weight loss in two different biodegradation media. PLLA/hb-PLLA blends showed more pronounced hydrophilic character and higher susceptibility to biodegradation with an increase in the degree of branching.     

Studies on the electronic transport and optical properties of some new chelate modified polysulfones in thin films

The studied polymers (chelate modified polysulfones) have been prepared by the polycondensation reaction between chloro‐end‐capped polysulfones and bis(2,4‐dihydroxybenzaldehyde)Cu²⁺ in the dymethyl sulfoxide/dichlormethane system, in the presence of an aqueous sodium hydroxide solution. The temperature dependence of electrical conductivity and Seebeck coefficient of the respective polymers was investigated using thin‐film samples, deposited from chloroform solutions onto glass substrates. The polymers under study have typical semiconducting properties. The values of some characteristic parameters of the investigated polymers (for example, activation energy of electrical conduction, ratio of carrier mobilities, etc.) have been determined. The nature of the electrical conduction mechanism is discussed. The values of the optical bandgap energy are determined from the absorption spectra. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 100–106, 2006     

Sorption of Cr(III)‐containing cations on strongly basic anion exchangers

It is shown that strongly basic anion exchangers AV‐17 and Varion‐AD in definite conditions are able to retain Cr(III)‐containing ions from Cr(III) sulfate solution. It is found that the sorption of Cr(III)‐containing ions on the polymers is essentially dependent on the pH, temperature, and Cr(III) sulfate concentration. The maximum temperature dependence of sorption was found to be about 60°C. The sorption isotherms are well described by Langmuir's equations. The sorption kinetics is determined by the diffusion of Cr(III)‐containing ions into polymer's phase. It is assumed that the Cr(III)‐containing ions are retained through formation, in polymer's phase, of the jarosite‐type mineral compounds: R₄N[Cr₃(OH)₆(SO₄)₂], H₃O[Cr₃(OH)₆(SO₄)₂], and K[Cr₃(OH)₆(SO₄)₂]. For comparison of sorptional capacities, the sorption of Cr(III)‐containing ions was determined on different cation and anion exchangers. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3978–3985, 2006     

Expedient Immobilization of TEMPO by Copper‐Catalyzed Azide‐Alkyne [3+2]‐Cycloaddition onto Polystyrene Resin

TEMPO was readily grafted by copper(I)‐catalyzed azide‐alkyne cycloaddition onto polystyrene. Starting with commercially available Merrifield resin (4.3 mmol/ g) almost quantitative loading of TEMPO onto the polymer was achieved (≥ 4 mmol/ g). The so obtained PS‐CLICK‐TEMPO allowed the oxidation of alcohols to aldehydes with bleach or molecular oxygen as the terminal oxidant with high yields and selectivity in multiple cycles without loss of activity.