Molecular hybridization strategy for tuning bioactive peptide function.

The physicochemical and structural properties of antimicrobial peptides (AMPs) determine their mechanism of action and biological function. However, the development of AMPs as therapeutic drugs has been traditionally limited by their toxicity for human cells. Tuning the physicochemical properties of such molecules may abolish toxicity and yield synthetic molecules displaying optimal safety profiles and enhanced antimicrobial activity.

Profile of MicroRNAs Associated with Death Due to Disease Progression in Metastatic Papillary Thyroid Carcinoma Patients.

Papillary thyroid carcinoma (PTC) is the most common neoplasm of the endocrine system and has an excellent long-term prognosis, with low rates of distant metastatic disease. Although infrequent, there are cases of deaths directly related to PTC, especially in patients with metastatic disease, and the factors that could be associated with this unfavorable outcome remain a major challenge in clinical practice. Recently, research into genetic factors associated with PTC has gained ground, especially mutations in the TERT promoter and BRAF gene.

Alterations of the Extracellular Matrix in Colorectal Carcinoma.

The process of proliferation and invasion of tumor cells depends on changes in the extracellular matrix (ECM) through the activation of enzymes and alterations in the profile of ECM components. Our aims were to investigate the mRNA and protein expression profiles of the ECM components, heparanase-1 (HPSE), heparanase-2 (HPSE2), matrix metalloproteinase-9 (MMP-9), and syndecan-1 (SDC1) in neoplastic and nonneoplastic tissues of 24 patients with colorectal carcinoma (CRC) and to test for associations between the expression patterns of these genes with the presence or absence of lymph node metastases. This was a cross-sectional study in which 24 adult patients with CRC were admitted for resectional surgery.

Resveratrol Decreases the Invasion Potential of Gastric Cancer Cells.

The cancer-preventive agent Resveratrol (RSV) [3,5,4'-trihydroxytrans-stilbene] is a widely recognized antioxidant molecule with antitumoral potential against several types of cancers, including prostate, hepatic, breast, skin, colorectal, and pancreatic. Herein, we studied the effect of RSV on the cell viability and invasion potential of gastric cancer cells. AGS and MKN45 cells were treated with different doses of RSV (0-200 μM) for 24 h.

Comment on Balsamo et al.: "Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature".

In this comment, we highlight the diagnosis of Birt-Hogg-Dubé (BHD) in a 60-year-old man was made from identification and removal of normochromic papular cutaneous lesions whose histological examination indicated trichodyscomas and which are considered equivalent to fibrofolliculomas, presence of bilateral renal mass suggestive of angiomyolipomas by imaging exams. A benign/likely benign variant of FLCN in the intron 13 was also detected. Still, his previous pathological history presented other relevant data such as the prior removal of vocal cord angioma, total thyroidectomy, and left parotidectomy due to a cystic lesion whose histopathological examination revealed the presence of oncocytoma and lipomatosis, in addition to basal cell cutaneous carcinoma.

Extracellular matrix alterations in the skin of patients affected by psoriasis.

Background: Psoriasis is a chronic inflammatory disease dependent upon a complex interaction between genetic predisposition and immunological factors. It is characterized by skin lesions throughout the body, causing great morbidity and affecting life quality. The present study aimed to evaluate the protein and mRNA expression of heparanase-1 (HPSE), heparanase-2 (HPSE2), syndecan-1 (SYND1), metalloproteinases (MMP2, MMP9), and tissue inhibitor metalloproteinases 2 (TIMP2) in skin samples.

The Heparan Sulfate Binding Peptide in Tumor Progression of Triple-Negative Breast Cancer.

Angiogenesis is the formation of new vessels from pre-existing vasculature. The heparan sulfate chains from endothelial cell proteoglycans interact with the major angiogenic factors, regulating blood vessels´ formation. Since the FDA´s first approval, anti-angiogenic therapy has shown tumor progression inhibition and increased patient survival.

Heparanase modulation by Wingless/INT (Wnt).

Heparanase is an endo-beta-glucuronidase, the only enzyme in mammals capable of cleaving heparan sulfate/heparin chains from proteoglycans. The oligosaccharides generated by heparanase present extensive biological functions since such oligosaccharides interact with adhesion molecules, growth factors, angiogenic factors and cytokines, modulating cell proliferation, migration, inflammation, and carcinogenesis. However, the regulation of heparanase activity is not fully understood.

MicroRNA-mediated extracellular matrix remodeling in squamous cell carcinoma of the oral cavity.

Background: We evaluated microRNAs and extracellular matrix component profiles in squamous cell carcinoma of the oral cavity (OSCC) in comparison to healthy mucosa.

Methods: Retrospective study investigating 64 microRNAs related to oncogenic process and to constituents of the extracellular matrix. We also performed immunohistochemical assays for molecules involved in the same biological processes.

MicroRNA-1252-5p Associated with Extracellular Vesicles Enhances Bortezomib Sensitivity in Multiple Myeloma Cells by Targeting Heparanase.

Introduction: Multiple myeloma (MM) remains an incurable disease, and patient survival requires a better understanding of this malignancy's molecular aspects. Heparanase (HPSE) is highly expressed in aggressive MM cells and related to tumor growth, metastasis, and bortezomib (BTZ) resistance. Thus, targeting HPSE seems to be a promising approach for MM treatment, and because microRNAs (miRNAs) have emerged as potential regulators of HPSE expression, the use of extracellular vesicles (EVs) can allow the efficient delivery of therapeutic miRNAs.

Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom.

VmCT1, a linear helical antimicrobial peptide isolated from the venom of the scorpion Vaejovis mexicanus, displays broad spectrum antimicrobial activity against bacteria, fungi, and protozoa. Analogs derived from this peptide containing single Arg-substitutions have been shown to increase antimicrobial and antiparasitic activities against Trypanossoma cruzi. Here, we tested these analogs against malaria, an infectious disease caused by Plasmodium protozoa, and assessed their antitumoral properties.

The Good and Bad Sides of Heparanase-1 and Heparanase-2.

In this chapter, we will emphasize the importance of heparan sulfate proteoglycans (HSPG) in controlling various physiological and pathological molecular mechanisms and discuss how the heparanase enzyme can modulate the effects triggered by HSPG. Additionally, we will also navigate about the existing knowledge of the possible role of heparanase-2 in biological events. Heparan sulfate is widely distributed and evolutionarily conserved, evidencing its vital importance in cell development and functions such as cell proliferation, migration, adhesion, differentiation, and angiogenesis.

Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature.

Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by benign growth of the hair follicles, the presence of pulmonary cysts, spontaneous pneumothorax, and bilateral renal tumors that are usually hybrid oncocytic or multifocal chromophobe renal cell carcinoma. The diagnosis is confirmed by the presence of a pathogenic variant in the tumor suppressor folliculin (FLCN) gene mapped at 17p11.2.

Horizontal histological sections in the preliminary evaluation of basal cell carcinoma submitted to Mohs micrographic surgery.

Background: Mohs micrographic surgery is a surgical technique for the treatment of nonmelanoma skin cancer. Surgery begins by removing the visible tumor before excision of the tissue specimens for evaluation of the tumor margins.

Objectives: To present a new way to evaluate the material obtained from debulking, by horizontal histological analysis of the fragment.

The effect of lysine substitutions in the biological activities of the scorpion venom peptide VmCT1.

Antimicrobial peptides (AMPs) are biologically active molecules with a broad-spectrum activity against a myriad of microorganisms. Aside from their antimicrobial functions, AMPs present physicochemical and structural properties that allow them to exert activity against other kind of cells, such as cancer cells. VmCT1 is a potent cationic amphipathic AMP from the venom of the scorpion Vaejovis mexicanus.

Crosstalk between tumor cells and lymphocytes modulates heparanase expression.

Background: Heparanase (HPSE) is an endo-beta-glucuronidase that degrades heparan sulfate (HS) chains on proteoglycans. The oligosaccharides generated by HPSE promote angiogenesis, tumor growth and metastasis. Heparanase-2 (HPSE2), a close homolog of HPSE, does not exhibit catalytic activity.

Heparanase-1 activity and the early postnatal prostate development.

Ventral prostate (VP) morphogenesis starts during embryonic development and continues for the first three postnatal weeks. Heparan sulfate (HS) affects paracrine signaling. Heparanase-1 (HPSE) is the only enzyme capable of cleaving HS.

Reflectance confocal microscopy as a tool for screening surgical margins of basal cell carcinoma.

Surgical excision of basal cell carcinoma with minimum margins requires serial assessment of layers by frozen histopathology in the case of Mohs micrographic surgery. Evaluation of presurgical tumor margins by in vivo reflectance confocal microscopy is a potential alternative. We selected 12 basal cell carcinoma lesions that were analyzed by confocal microscopy to define margins.

Is surgical debridement necessary in the diabetic foot treated with photodynamic therapy?

: Diabetic patients are susceptible to developing foot ulcers with serious complications such as osteomyelitis and amputations. Treatment approaches are still empirical and the benefit of usual procedures such as surgical debridement has not been properly evaluated. Photodynamic Therapy (PDT) is a non-invasive and highly efficient method for the treatment of the diabetic foot, being able to eradicate the infection and to stimulate healing, decreasing considerably the amputation risk.

Extracellular matrix alterations in the Peyronie's disease.

Peyronie's disease is characterized by fibrous plaque formation of the tunica albuginea, causing penile deformity and fertility problems. The aim of the present study was to investigate alterations in the extracellular matrix in Peyronie's disease. The study used tissues collected by surgical procedure from individuals that presented a well-established disease, while control samples were obtained by biopsies of fresh cadavers.

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

Background:: Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer.

STUDIES OF MOLECULAR CHANGES IN INTERVERTEBRAL DISC DEGENERATION IN ANIMAL MODEL.

Objective: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model.

Methods: Wistar rats underwent intervertebral disc degeneration through 20-gauge needle puncture, and 360° rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15(th) and 28(th) days after degenerative induction.

EVALUATION OF THE EXTRACELLULAR MATRIX OF INJURED SUPRASPINATUS IN RATS.

Objective: To evaluate the evolution of injuries of the supraspinatus muscle by immunohistochemistry (IHC) and anatomopathological analysis in animal model (Wistar rats).

Methods: Twenty-five Wistar rats were submitted to complete injury of the supraspinatus tendon, then subsequently sacrificed in groups of five animals at the following periods: immediately after the injury, 24h after the injury, 48h after, 30 days after and three months after the injury. All groups underwent histological and IHC analysis.

The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms.

Introduction: The search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase (HPSE) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 (HPSE2) modulates HPSE activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions.

Development of the Tardivo Algorithm to Predict Amputation Risk of Diabetic Foot.

Diabetes is a chronic disease that affects almost 19% of the elderly population in Brazil and similar percentages around the world. Amputation of lower limbs in diabetic patients who present foot complications is a common occurrence with a significant reduction of life quality, and heavy costs on the health system. Unfortunately, there is no easy protocol to define the conditions that should be considered to proceed to amputation.