Platelet lysate and adipose mesenchymal stromal cells on silk fibroin nonwoven mats for wound healing

In this work platelet lysate (PL) and adipose‐derived mesenchymal stromal cells (ASCs) seeded on nonwoven fibroin mats were in vitro and in vivo evaluated for tissue regenerative applications. Nonwoven mats obtained by a large scale water entanglement technique were characterized for their physico‐chemical properties. Results indicated a high purity of fibroin fibers, their stability after sterilization process and appropriate technological properties suitable for tissue engineering. Moreover, the scaffolds in vitro supported adhesion and migration of ASCs and the presence of PL improved the cell proliferation. The products were then applied on epithelial/dermal wounds carried out on the dorsal surface of rabbit: the skin reparative process was solved in 9 days, with a completely restitutio ad integrum of the epithelium in animals treated with PL alone; ASCs did not further improve the wound healing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42942.     

Activity of Fluorine‐Containing Analogues of WC‐9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii

Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC‐9 (4‐phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells. Two fluorine‐containing derivatives, the 3‐(3‐fluorophenoxy)‐ and 3‐(4‐fluorophenoxy)phenoxyethyl thiocyanates, exhibited half‐maximal effective concentration (EC₅₀) values of 1.6 and 4.9 μm , respectively, against tachyzoites of T. gondii, whereas they showed similar potency to WC‐9 against intracellular T. cruzi (EC₅₀ values of 5.4 and 5.7 μm , respectively). In addition, 2‐[3‐ (phenoxy)phenoxyethylthio]ethyl‐1,1‐bisphosphonate, which is a hybrid inhibitor containing 3‐phenoxyphenoxy and bisphosphonate groups, has activity against T. gondii proliferation at sub‐micromolar levels (EC₅₀=0.7 μm ), which suggests a combined inhibitory effect of the two functional groups.     

Montmorillonite reinforced type A gelatin nanocomposites

This study investigates the structural, morphological, thermal, and mechanical properties of type A gelatin/montmorillonite (MMT) films as a function of MMT concentration. The variations of the X‐ray diffraction pattern suggest that the structure of the nanocomposites turns from intercalated to exfoliated on increasing clay loading up to 20 wt %. Simultaneously, gelatin interaction with clay negative sheets during gelling provokes a reduction of the triple helix content of the composite films, in agreement with the reduction of the relative intensity of the 1.1 nm diffraction reflection of gelatin and of the values of denaturation enthalpy. On the other hand, the increase of the denaturation and decomposition temperatures, the significant rise of the Young's modulus, as well as the swelling decrease observed as clay content increases, demonstrate a relevant stabilizing effect of MMT on gelatin. The reinforcement action of MMT allows to utilize a relatively low concentration of the crosslinking agent genipin to further stabilize the films. The synergic action of clay and genipin prevents dissolution of the nanocomposites in aqueous solution and enhances their mechanical properties. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40301.     

Impact of Spatially Heterogeneous Trop-2 Expression on Prognosis in Oral Squamous Cell Carcinoma

Oral cancer often presents with aggressive behavior and a high risk of recurrence and metastasis. For oral squamous cell carcinoma (OSCC), which is the most frequent histological subtype, therapy strategies include surgery, radiation therapy, chemotherapy, immune checkpoint inhibitors, and EGFR inhibitors. Recently, a Trop-2 antibody-drug conjugate (ADC) has been approved in the United States of America for the treatment of advanced triple-negative breast cancer. However, this ADC has also been tested in other solid tumors including head & neck squamous cell carcinoma. The prognostic impact of Trop-2 has already been reported for several cancers. We studied the prognostic influence of Trop-2 protein expression on OSCC patients’ survival. The cohort comprised n = 229 OSCC patients with available archived tumor tissue and corresponding non-neoplastic oral mucosa tissue. Using immunohistochemistry, we investigated Trop-2 expression in both the central and peripheral regions of each tumor and in corresponding non-neoplastic oral mucosa. In patients suffering from OSCC with combined high central and low peripheral Trop-2 expression, five-year overall survival (OS) was 41.2%, whereas 55.6% of OSCC patients who presented lower central and/or higher peripheral tumoral Trop-2 expression were alive after five years (p = 0.075). In multivariate Cox regression, the expression pattern of high central tumoral and lower peripheral Trop-2 expression was significantly correlated with impaired OS (HR = 1.802, 95%-CI: 1.134–2.864; p = 0.013) and recurrence-free survival (RFS) (HR = 1.633, 95%-CI: 1.042–2.560; p = 0.033), respectively, when adjusting for co-variables. Hence, Trop-2 may serve as an independent prognostic biomarker in OSCC. In subsequent studies, the pathophysiological meaning of downregulated Trop-2 expression in the OSCC periphery has to be analyzed.     

Effect of Processing on the Physico-Chemical Characteristics of Quinoa Flour (Chenopodium quinoa,Willd)

The nature and extent of the modification of starch in quinoa, caused by various processes like cooking and autoclaving of the seeds, drum drying of the flour and extrusion of the grits was investigated by measuring the physico-chemical properties - the water absorption, water solubility, swelling power, viscosity and degree of gelatinisation - of the processed samples. Autoclaved samples showed the lowest degree of gelatinisation (32.5% by DSC) of the starch, while the degree of gelatinisation of the precooked/drum dried samples was found to be 97.4% by DSC method. Higher polymer degradation was observed in cooked samples than in autoclaved samples as seen in the gel chromatographic separation. The water solubility in cooked samples (5.44 to 15.58) and in autoclaved samples (7.02 to 9.64) increased with the process time. In the extrusion process, the moisture content as well as the compression ratio was found to affect the degree of starch modification significantly (p <0.01).     

Thermal and flammability properties influenced by Zn/Al,Co/Al,and Ni/Al layered double hydroxide in low-density polyethylene nanocomposites

Layered double hydroxide (LDH) containing different metal constituents (Zn, Co, and Ni) was intercalated with different organic anions and has been used as fillers in low-density polyethylene (LDPE), and its thermal and flammability behavior was evaluated. The best thermal stability (∆T_0.5 = 21 °C) was obtained with the LDPE-Ni/Al-dodecyl sulfate (4 wt %) nanocomposite. Addition of hydrophobic LDHs systematically decreases the enthalpy of melting and crystallization compared to the neat polymer. In LDPE-Co/Al-dodecyl sulfate (2 wt %) nanocomposite, the melting and crystallization enthalpies declined by about 45 J/g, indicating a good interaction of the filler with the polymer matrix. A reduction of 20% of the flammability for the LDPE-Ni/Al-stearate (4 wt %) nanocomposite was obtained. On the other hand, Zn–Co LDH as filler in LDPE nanocomposite did not affect effectively the same property. In an innovative study, results indicate that different metal constituents and interlayer anion of LDH as filler can change thermal and flammability properties of the polymer nanocomposite. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48737.     

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT₁ receptors and NADPH oxidase, and lower expression of AT₂, Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.     

PDGF/PDGFR: A Possible Molecular Target in Scleroderma Fibrosis

Systemic sclerosis (SSc) is a clinically heterogeneous disorder of the connective tissue characterized by vascular alterations, immune/inflammatory manifestations, and organ fibrosis. SSc pathogenesis is complex and still poorly understood. Therefore, effective therapies are lacking and remain nonspecific and limited to disease symptoms. In the last few years, many molecular and cellular mediators of SSc fibrosis have been described, providing new potential options for targeted therapies. In this review: (i) we focused on the PDGF/PDGFR pathway as key signaling molecules in the development of tissue fibrosis; (ii) we highlighted the possible role of stimulatory anti-PDGFRα autoantibodies in the pathogenesis of SSc; (iii) we reported the most promising PDGF/PDGFR targeting therapies.