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The present study evaluated the role of heme oxygenase 1 (HO-1)/carbon monoxide (CO) pathway in the cholera toxin-induced diarrhea and its possible action mechanism. The ...pharmacological modulation with CORM-2 (a CO donor) or Hemin (a HO-1 inducer) decreased the intestinal fluid secretion and Cl− efflux, altered by cholera toxin. In contrast, ZnPP (a HO-1 inhibitor) reversed the antisecretory effect of Hemin and potentiated cholera toxin-induced intestinal secretion. Moreover, CORM-2 also prevented the alteration of intestinal epithelial architecture and local vascular permeability promoted by cholera toxin. The intestinal absorption was not altered by any of the pharmacological modulators. Cholera toxin inoculation also increased HO-1 immunoreactivity and bilirubin levels, a possible protective physiological response. Finally, using fluorometric technique, ELISA assay and molecular docking simulations, we show evidence that CO directly interacts with cholera toxin, forming a complex that affects its binding to GM1 receptor, which help explain the antisecretory effect. Thus, CO is an essential molecule for protection against choleric diarrhea and suggests its use as a possible therapeutic tool.
Introduction
There are no drugs specifically approved to treat cutaneous lupus. Inflammatory cells in lupus skin lesions can produce leukotrienes (LT), which promote tissue damage. In addition to ...hypersensitivity reactions, LT are also associated with cardiovascular diseases and elevated serum LT levels have been linked to worse atherosclerotic disease in lupus. Targeting LT could thus be an alternative to treat lupus. We present 4 cases of cutaneous lupus successfully treated with montelukast (MLK), a Cys‐LT antagonist.
Methods
Four consecutive female systemic lupus erythematosus (SLE) patients with refractory skin lesions were treated with MLK (10 mg/d) in the Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará. Skin lesions were scored using Revised Cutaneous LE Disease Area and Severity Index (RCLASI). Relative expression of the 5‐lipoxigenase (ALOX5) and 15‐lipoxigenase (ALOX15) genes was determined in peripheral blood cells (PBC) from lupus patients and 4 age‐matched female controls.
Results
All patients experienced improvement of skin lesions measured using RCLASI scores within 2–12 weeks following initiation of MLK. The response was sustained for at least 3 months follow‐up and no adverse events were recorded. ALOX5 but not ALOX15 gene expression was significantly (P = 0.0425) increased in PBC from SLE patients vs controls.
Conclusion
This is the first report of a fast and sustained successful response of cutaneous lupus to MLK. Given its acceptable safety profile, our data encourage development of a randomized trial as an attempt to reposition MLK as a safe, affordable alternative to treat cutaneous lupus.
Polymeric biomaterials composed of extracellular matrix components possess osteoconductive capacity that is essential for bone healing. The presence of collagen and the ability to undergo ...physicochemical modifications render these materials a suitable alternative in bone regenerative therapies. The objective of this study was to evaluate the osteogenic capacity of collagen-based matrices (native and anionic after alkaline hydrolysis) made from bovine intestinal serosa (MBIS). Twenty-five animals underwent surgery to create a cranial defect to be filled with native and anionic collagen matrixes, mmineralized and non mineralized. The animals were killed painlessly 6 weeks after surgery and samples of the wound area were submitted to routine histology and morphometric analysis. In the surgical area there was new bone formation projecting from the margins to the center of the defect. More marked bone neoformation occurred in the anionic matrices groups in such a way that permitted union of the opposite margins of the bone defect. The newly formed bone matrix exhibited good optical density of type I collagen fibers. Immunoexpression of osteocalcin by osteocytes was observed in the newly formed bone. Morphometric analysis showed a greater bone volume in the groups receiving the anionic matrices compared to the native membranes. Mineralization of the biomaterial did not increase its osteoregenerative capacity. In conclusion, the anionic matrix exhibits osteoregenerative capacity and is suitable for bone reconstruction therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To investigate the participation of canonical Wnt and NF-κB signaling pathways in an experimental model of chronic arthritis induced by methylated bovine serum albumin (mBSA) in rat ...temporomandibular joint (TMJ).
Materials and methods
Wistar rats were sensitized by mBSA+Complete Freund Adjuvant (CFA)/Incomplete Freund Adjuvant (IFA) on the first 14 days (1 ×/week). Subsequently, they received 1, 2 or 3 mBSA or saline solution injections into the TMJ (1 ×/week). Hypernociceptive threshold was assessed during the whole experimental period. 24 h after the mBSA injections, the TMJs were removed for histopathological and immunohistochemical analyses for TNF-α, IL-1β, NF-κB, RANKL, Wnt-10b, β-catenin and DKK1.
Results
The nociceptive threshold was significantly reduced after mBSA injections. An inflammatory infiltrate and thickening of the synovial membrane were observed only after mBSA booster injections. Immunolabeling of TNF-α, IL-1β and Wnt-10b was increased in the synovial membrane in arthritic groups. The immunoexpression of nuclear β-catenin was significantly higher only in the group that received 2 booster TMJ injections. However, NF-κB, RANKL and DKK1 immunoexpression were increased only in animals with 3 mBSA intra-articular injections.
Conclusion
Our results suggest that canonical Wnt and NF-κB signaling pathways participate in the hypernociception and inflammatory response in TMJ synovial membrane during the development of rheumatoid arthritis in rats.
•Rotenone induces mitochondria dysfunction in astrocytes;•Rotenone increases NF-kB expression in astrocytes;•Rotenone also increases Nrf2 expression in astrocytes;•These effects are possibly a ...consequence of the rotenone-induced oxidative stress;•Vitamin D improves cell viability and prevents all these rotenone effects, pointing to its neuroprotective actions and possible benefits in neurodegenerative diseases as PD.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic cells in the substantia nigra pars compacta. PD patients’ brains show neuroinflammation, oxidative stress, and mitochondrial dysfunction. The present study aims to evaluate the neuroprotective activity of VD3 on astrocytes after their exposure to rotenone (ROT) a natural pesticide known to exhibit neurotoxic potential via the inhibition of mitochondrial complex I. Cell viability parameters were evaluated by the MTT test and staining with 7-AAD in cultures of astrocytes treated and untreated with VD3 (0.1, 0.5, and 1.0 ng/mL) and/or ROT (10 µg/mL or 5 µg/mL), and the cytoplasmic production of ROS and the cell death profile were measured by flow cytometry. Glutathione accumulation and ultrastructural changes were evaluated and immunocytochemistry assays for NF-kB and Nrf2 were also carried out. The results showed that VD3 improved the viability of cells previously treated with VD3 and then exposed to ROT, reducing the occurrence of necrotic and apoptotic events. Furthermore, cells exposed to ROT showed increased production of ROS, which decreased significantly with previous treatment with VD3. Importantly, the decrease by ROT in the mitochondrial transmembrane potential was significantly prevented after treating cells with VD3, especially at a concentration of 1 ng/mL. Therefore, treatment with VD3 protected astrocytes from damage caused by ROT, decreasing oxidative stress, decreasing NF-kB and Nrf2 expressions, and improving mitochondrial function. However, further investigation is needed regarding the participation and mechanism of action of VD3 in this cellular model of PD focusing on the crosstalk between Nrf2 and NF-kB.
Biomaterials have been investigated as an alternative for the treatment of bone defects, such as chitosan/carbon nanotubes scaffolds, which allow cell proliferation. However, bone regeneration can be ...accelerated by electrotherapeutic resources that act on bone metabolism, such as low-level laser therapy (LLLT). Thus, this study evaluated the regeneration of bone lesions grafted with chitosan/carbon nanotubes scaffolds and associated with LLLT. For this, a defect (3 mm) was created in the femur of thirty rats, which were divided into 6 groups: Control (G1/Control), LLLT (G2/Laser), Chitosan/Carbon Nanotubes (G3/C+CNTs), Chitosan/Carbon Nanotubes with LLLT (G4/C+CNTs+L), Mineralized Chitosan/Carbon Nanotubes (G5/C+CNTsM) and Mineralized Chitosan/Carbon Nanotubes with LLLT (G6/C+CNTsM+L). After 5 weeks, the biocompatibility of the chitosan/carbon nanotubes scaffolds was observed, with the absence of inflammatory infiltrates and fibrotic tissue. Bone neoformation was denser, thicker and voluminous in G6/C+CNTsM+L. Histomorphometric analyses showed that the relative percentage and standard deviations (mean ± SD) of new bone formation in groups G1 to G6 were 59.93 ± 3.04a (G1/Control), 70.83 ± 1.21b (G2/Laser), 70.09 ± 4.31b (G3/C+CNTs), 81.6 ± 5.74c (G4/C+CNTs+L), 81.4 ± 4.57c (G5/C+CNTsM) and 91.3 ± 4.81d (G6/C+CNTsM+L), respectively, with G6 showing a significant difference in relation to the other groups (a ≠ b ≠ c ≠ d; p < 0.05). Immunohistochemistry also revealed good expression of osteocalcin (OC), osteopontin (OP) and vascular endothelial growth factor (VEGF). It was concluded that chitosan-based carbon nanotube materials combined with LLLT effectively stimulated the bone healing process.
A imposição de isolamento social decorrente da pandemia da Covid-19 desencadeou a suspensão das aulas presenciais em toda rede pública e privada de ensino no Brasil. Com isso, docentes de ...instituições privadas de cursos superiores presenciais de turismo se depararam com a realidade de lecionar longe da convencional sala de aula, tendo que transpor o planejamento pedagógico pautado no ensino presencial para o ensino remoto. Perante essa conjuntura, o objetivo geral desta pesquisa foi investigar as experiências desses docentes devido à implementação do ensino remoto. Quanto aos procedimentos metodológicos, adotou-se a abordagem qualitativa, tendo como instrumento de coleta de dados entrevistas semiestruturadas online com docentes de cursos presenciais de bacharelado em turismo de instituições privadas no estado do Rio de Janeiro, no período de 21 a 28 de maio de 2020. A sistematização e análise de dados ocorreu baseada na pesquisa de Estrada-Villa (2014), concomitantemente ao uso dos pressupostos de análise categorial-temática de Bardin (2011). Como resultados, identificou-se oito categorias: (1) atitude e interesse; (2) características dos estudantes; (3) política da Instituição de Ensino Superior; (4) ferramentas e recursos tecnológicos; (5) treinamento; (6) capacitação docente; (7) ambiente de trabalho e trabalho de reprodução social; (8) condições físicas e psicológicas. Logo, o ensino remoto não apenas expôs o problema da desigualdade ao acesso à tecnologia digital, mas também vários outros problemas que atingem tanto docentes quanto discentes: ambiência para estudos; saúde mental-psicológica; e falta de políticas públicas direcionadas à primeira infância para auxiliar mães e pais docentes.
Palavras-chave: Covid-19. Trabalho Docente. Ensino Remoto. Turismo.
Heparanase is an endo-β-glucuronidase that is capable of degrading heparan sulfate chains of proteoglycans, generating a variety of bioactive molecules such as growth factors and chemotactic and ...angiogenic agents. The expression of heparanase was investigated in the peripheral blood mononuclear cell fraction (PBMC) of 30 patients with breast cancer and 20 healthy control women by reverse transcription—polymerase chain reaction (RT-PCR) and immunocytochemistry. PBMC samples from all breast cancer patients at study entry showed the expression of heparanase, whereas no expression was observed for healthy women. Immunocytochemistry analysis demonstrated that heparanase was expressed in lymphocytes of breast cancer PBMC. Throughout follow-up, heparanase expression by RTPCR decreased significantly after surgery in patients treated with neoadjuvant chemotherapy (P = .002) and after tamoxifen treatment (P = .040), whereas it increased significantly with the advent of systemic metastasis (P = .027). In vitro, either serum from breast cancer patients or a medium originated from coculture experiments of MCF-7 cells and lymphocytes from healthy women stimulated heparanase expression in normal lymphocytes. The results suggest that there is a tumor-inducing effect on heparanase expression by lymphocytes present in the PBMCs of breast cancer patients, which depends, in turn, on the interaction between a tumor and normal lymphocytes.
The treatment of chronic wounds is considered a public health problem. When the condition affects at-risk groups such as those with diabetics, it becomes a great clinical challenge. In this work, we ...evaluated the healing effects of a new zinc complex, Zn(phen)(van)
, identified as ZPV, which was synthesized, characterized and associated with chitosan (CS) membranes and tested on cutaneous wounds of diabetic rats. Chitosan membranes were modified by Schiff base reaction with the complex under two experimental conditions (14 and 21 days), resulting in membranes with concentrations of complex equal to 0.736 μmol cm
(CS-ZPV1) and 1.22 μmol cm
(CS-ZPV2). Release assays in aqueous medium indicated that the membranes release the complex gradually when exposed to an aqueous medium. Diabetes was inducted in
rats using 40 mg/kg (i.v.) streptozotocin. On the 7th day after diabetic induction, a circular excision on the skin (1.0 cm) was performed with a punch. The lesions were treated with the pure chitosan membrane and the membrane associated with the zinc-vanillin complex in two different doses. Skin samples were subjected to macroscopic and histopathological analyses, cytokine (TNF-α, IL-1β, and IL-10) quantification and reverse transcriptase polymerase chain reaction (TGF-β and VEGF) assays. The analyses showed a decrease in wound size, reepithelialization, angiogenic stimulus, collagen deposition, and reduced levels of TNF-α and IL-1β as well as increased IL-10 and gene expression of TGF-β and VEGF. The evaluated parameters suggest that CS-ZPV in the two concentrations tested may be effective in the treatment of chronic wounds.
Clostridioides difficile
infection (CDI) is the leading cause of healthcare-associated diarrhea. This infection can particularly affect older adults, the most susceptible to CDI. Currently, the ...standard therapeutic measure is antibiotic therapy, which in turn increases the risk of recurrence of the infection by its collateral damage to the patient’s microbiota. Probiotics are live microorganisms capable of maintaining balance in the intestinal microbiota. This study aims to perform an integrative review of the protective benefit of probiotics in CDI and diarrhea associated with
C. difficile
. The PubMed, Scopus, and Web of Science databases, the 10-year time cutoff, and the Prism Flow diagram were used for data collection. We observed no consensus among the studies; however, three of the seven evaluated studies demonstrated that the use of probiotics in older adults could contribute to reducing the incidence of hospital-onset CDI. We also found that the studies evaluated a wide variety of microorganisms, particularly
Saccharomyces boulardii
, associated with beneficial effects. More research is needed to understand the successful use of probiotics in the prevention of CDI in hospitalized older adults receiving antibiotics.
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