Transforming growth factor beta-1 and vascular endothelial growth factor in the recovery and formation of skin scars

Relevance. Scars are multi-tissue structures that significantly reduce the quality of life of the young, able-bodied population. The most socially significant variants are represented by hypertrophic and keloid postoperative scars and scars after burns, atrophic scars after acne vulgaris and striae. Growth factors, which are also used for their treatment, play a significant role in their formation and progression. The aim of this work is to summarize data on the participation of growth factors (transforming growth factor beta-1 and vascular endothelial growth factor) in the formation of a hypertrophic or atrophic scar. Materials and Methods. The study of literary sources of scientometric scientific bases was carried out. Results and Discussion . The study showed that the duration of the scarring phases preceding it is of great importance in scar formation, their prolongation leads to chronic inflammation and the attachment of an autoimmune component, an increase in the number of myofibroblasts due to inhibition of apoptosis and an increase in the synthesis of intercellular substance and immature forms of collagen, as well as thinning of the epidermis over scar. Growth factors such as growth factor beta-1 and vascular endothelial growth factor are capable of shifting the balance of these two main pathways or towards proliferative processes, contributing to an increase in the number of blood vessels in the hemomicrocirculatory bed, the number of mast cells and total cellularity, as well as, in some cases, the synthesis of keloid - that is, the formation of a hypertrophic or keloid scar. On the contrary, the prevalence of inflammatory processes leads to a decrease in cellularity, a decrease in blood vessels and intercellular substance, as well as damage to elastin and collagen fibers, forming the phenotype of an atrophic scar or striae. Conclusion. Growth factors play a key role in scar formation, contributing to an increase in the number of blood vessels in the hemomicrocirculatory bed, the number of mast cells and total cellularity, as well as, in some cases, the synthesis of keloid - that is, the formation of a hypertrophic or keloid scar.

Nutritional Support With Oral Polymeric Formulation Enriched With Transforming Growth Factor beta 2 (TGF-β2) in Allogenic Hematopoietic Stem Cells Transplantation (Allo-hsct): A Prospective Interventional Study

PurposeIn the allogeneic transplant setting (allo-HSCT), the prevalence of malnutrition at admission is usually low, but at discharge, may be 60% or more and it may affect the transplant outcome.The aim of this study was to reduce the incidence of severe malnutrition (PG-SGA C) at day + 28 days from allo-HSCT in patients supported with an oral polymeric formulation enriched with Transforming Growth Factor beta 2 (TGF-β2).MethodsFifty-one patients were consecutively enrolled between March 2020 and June 2021 in this prospective interventional study. As a group of control, we have retrospectively analyzed an observational cohort composed by thirty patients submitted to allo-HSCT from august 2017 and august 2018 in our institution.ResultsThe incidence of severe malnourished patients (PG-SGA C) at + 28 days was significantly lower in the group with an oral nutritional support (ONS) treatment ratio (TR) major than 50% (TR>50%) in comparison to the ones with less than 50% ONS assumption (TR<50%) (13% vs 88.9% P=0.000). Interestingly, cumulative incidence of gastrointestinal (GI) aGVHD was significantly lower in patients assuming 50% or more of the prescribed ONS dose in comparison to those who assumed less than 50% of ONS (0%, vs 29.6%; p=0.005). Pneumonia was more frequent in patients with TR < 50% compared to patients with TR > 50% (48.1 % and 12.5 % respectively)(p=0.006).ConclusionMODULEN-IBD® seems to be a promising ONS to reduce malnutrition in allogeneic stem cell transplantation and should be tested in a randomized controlled prospective trial. MODULEN-IBD® may also have some positive immunological effects on gastrointestinal GVHD and infections that should be explored in larger studies.

Correlation between Oxidative Stress and Transforming Growth Factor-Beta in Cancers

The downregulation of reactive oxygen species (ROS) facilitates precancerous tumor development, even though increasing the level of ROS can promote metastasis. The transforming growth factor-beta (TGF-β) signaling pathway plays an anti-tumorigenic role in the initial stages of cancer development but a pro-tumorigenic role in later stages that fosters cancer metastasis. TGF-β can regulate the production of ROS unambiguously or downregulate antioxidant systems. ROS can influence TGF-β signaling by enhancing its expression and activation. Thus, TGF-β signaling and ROS might significantly coordinate cellular processes that cancer cells employ to expedite their malignancy. In cancer cells, interplay between oxidative stress and TGF-β is critical for tumorigenesis and cancer progression. Thus, both TGF-β and ROS can develop a robust relationship in cancer cells to augment their malignancy. This review focuses on the appropriate interpretation of this crosstalk between TGF-β and oxidative stress in cancer, exposing new potential approaches in cancer biology.

Genetic Biomarkers in Chronic Myeloid Leukemia: What Have We Learned So Far?

Chronic Myeloid Leukemia (CML) is a rare malignant proliferative disease of the hematopoietic system, whose molecular hallmark is the Philadelphia chromosome (Ph). The Ph chromosome originates an aberrant fusion gene with abnormal kinase activity, leading to the buildup of reactive oxygen species and genetic instability of relevance in disease progression. Several genetic abnormalities have been correlated with CML in the blast phase, including chromosomal aberrations and common altered genes. Some of these genes are involved in the regulation of cell apoptosis and proliferation, such as the epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), or Schmidt-Ruppin A-2 proto-oncogene (SRC); cell adhesion, e.g., catenin beta 1(CTNNB1); or genes associated to TGF-β, such as SKI like proto-oncogene (SKIL), transforming growth factor beta 1 (TGFB1) or transforming growth factor beta 2 (TGFB2); and TNF-α pathways, such as Tumor necrosis factor (TNFA) or Nuclear factor kappa B subunit 1 (NFKB1). The involvement of miRNAs in CML is also gaining momentum, where dysregulation of some critical miRNAs, such as miRNA-451 and miRNA-21, which have been associated to the molecular modulation of pathogenesis, progression of disease states, and response to therapeutics. In this review, the most relevant genomic alterations found in CML will be addressed.