Oral administration of botryosphaeran [(1 → 3)(1 → 6)-ß-d-glucan] reduces inflammation through modulation of leukocytes and has limited effect on inflammatory nociception.

Several biological activities of the fungal exopolysaccharide (1 → 3)(1 → 6)-ß-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal ß-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal ß-glucan a new possibility for complementary treating acute and chronic inflammation.

More than just acral melanoma: the controversies of defining the disease.

Acral melanoma (AM) is a malignant cutaneous melanocytic tumour specifically located on the palms, soles, and nail apparatus, which are areas of glabrous (hairless) skin. Acral lentiginous melanoma, a subtype of AM, represents a histopathological subtype diagnosis of cutaneous melanoma with unique morphological and structural features. Despite clear definitions, the misuse of these terms and the inconsistency in reporting the histopathological features of AM cases have become a major obstacle to the study of the disease. In this review, we discuss the epidemiology, histopathological features, prognosis, and genetic profile of AM, highlighting the differences observed when histopathological subtypes are considered. The increasing global effort to characterise AM cases from ethnically diverse populations would benefit greatly from a more consistent classification of the disease.

The progression of metastatic melanoma augments a pro-oxidative milieu locally but not systemically.

Malignant melanoma is the most dangerous form of skin cancer. Despite new therapies for melanoma treatment, effective therapy is mainly limited by excessive metastasis. Currently, the factors determining metastasis development are not elucidated, but oxidative stress was suggested to be involved. To this end, we analyzed oxidative stress parameters during the metastatic development using the syngeneic B16F10 melanoma model. An increase in blood plasma lipid peroxidation occurred at the earliest stage of the disease, with a progressive decrease in oxidative damage and an increase in antioxidant defense. Vice versa, increased lipid peroxidation and 3-nitrotyrosine, and decreased antioxidant parameters were observed in the metastatic nodules throughout the disease. This was concomitant with a progressive increase in vascular endothelial growth factor and proliferating cell nuclear antigen. We conclude that the oxidative stress in the bloodstream decreases during the metastatic process and that nitrosative stress increases during the proliferation and growth of metastatic nodules in the tumor microenvironment. These results will help to better understand the role of oxidative stress during melanoma metastasis.

Metformin: oxidative and proliferative parameters in-vitro and in-vivo models of murine melanoma.

Cutaneous melanoma is one of the most lethal cancers because of its increased rate of metastasis and resistance to available therapeutic options. Early studies indicate that metformin has beneficial effects on some types of cancer, including melanoma. To clarify knowledge of the mechanism of action of metformin on this disease, two treatment-based approaches are presented using metformin on melanoma progression: an in-vitro and an in-vivo model. The in-vitro assay was performed for two experimental treatment periods (24 and 48 h) at different metformin concentrations. The results showed that metformin decreased cell viability, reduced proliferation, and apoptosis was a major event 48 h after treating B16F10 cells. Oxidative stress was characterized by the decrease in total thiol antioxidants immediately following 24 h of metformin treatment and showed an increase in lipid peroxidation. The in-vivo model was performed by injecting B16F10 cells into the subcutaneous of C57/BL6 mice. Treatment with metformin began on day 3 and on day 14, the mice were killed. Treatment of mice with metformin reduced tumor growth by 54% of its original volume compared with nontreatment. The decrease in systemic vascular endothelial growth factor, restoration of antioxidants glutathione and catalase, and normal levels of lipid peroxidation indicate an improved outcome for melanoma following metformin treatment, meeting a need for new strategies in the treatment of melanoma.

Isoflavin-ß modifies muscle oxidative stress and prevents a thyrotoxicosis-induced loss of muscle mass in rats.

INTRODUCTION: We sought to verify whether isoflavin-beta (Iso-ß), a mixture of isoflavones with antioxidant properties, could prevent thyrotoxicosis-induced loss of muscle mass and the participation of oxidative stress (OS) in the mechanisms of this prevention. METHODS: Two experimental periods of thyrotoxicosis induction were used in Wistar rats: 3 and 5 days to assess Iso-ß effects before and after thyrotoxicosis-induced muscle wasting. After euthanasia, peritoneal fat and gastrocnemius muscle were collected, weighed, and muscle OS was assessed. RESULTS: Iso-ß prevented the loss of gastrocnemius mass in thyrotoxic rats through the prevention of muscle OS generation during thyrotoxicosis, increasing muscle total antioxidant capacity and decreasing mitochondrial cytochrome c oxidase activity, lipid peroxidation, and protein carbonyl content. CONCLUSION: Iso-ß decreased oxidative modification of proteins, which is known to exert a major role during proteolysis induction and is present in thyrotoxic myopathy, highlighting the potential action of Iso-ß in this complication of the disease. Muscle Nerve 56: 975-981, 2017.

Involvement of regulatory T cells in HIV immunopathogenesis.

Recently, a mechanism of negative regulation of immune responses by a specialized population of so-called regulatory T cells (Tregs) has become a focus of intense investigation. Through the discovery of transcription factor Foxp3 as a central molecular determinant of Tregs differentiation and function, the complex biology of these cells, including maintenance of immunological tolerance to "self" and regulation of immune responses to pathogens, commensals, and tumors, has become the focus of intense investigation. The ability to control the infection and to delay the progression of the infection to AIDS and/or death is probably regulated by a balance between host factors, such as immunologic response and viral factors. Different rates of disease progression among HIV-1 infected individuals have been observed. In this context, Tregs may play an important role in the immunopathology of HIV-1 infection due to their potent suppressive activity of both T cell activation and effector function. In this review, we present the molecular and immunological aspects of Tregs in the HIV system and the association between Tregs and highly active antiretroviral therapy (HAART).