Chemical characterization and antineoplastic effect of oligosaccharides from Cabernet Franc red wine in mammary tumor model in mice.

The present study characterized oligosaccharide compounds (Oligo) in Cabernet Franc red wine and investigated its antineoplastic effects against mammary tumor cells in vivo and in vitro, isolated or in combination with chemotherapy. The Oligo fraction was characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. The complex mixture of Oligo showed high amounts of oligoxyloglucuronans, oligorhamnogalacturonans, oligoarabinogalactans, and oligoglucans, such as trehalose and isomaltotriose. To investigate the antineoplastic effects of Oligo, Female Swiss mice were subcutaneously inoculated with Ehrlich tumor cells and then received vehicle (distilled water, p.o.), Oligo solution (9, 35, or 70 mg/kg, p.o.), or methotrexate (1.5 mg/kg, i.p.). The treatments were administered in a conventional (21-d) or chemopreventive (42-d) protocol. Oligo reduced the growth of Ehrlich tumors in both protocols and increased the effectiveness of methotrexate in controlling tumor growth. Oligo did not reduce the viability of MCF-7, MDA-MB-231, MDA-MB-436, and HB4a human breast cells that were cultured for 48 h, showing no cytotoxicity. Overall, Oligo exerted an in vivo antineoplastic effect and modulated immune blood cells, dependent on treatment time, and was not directly cytotoxic to tumor cells. Thus, Oligo may indirectly regulate tumor cell development and may be a promising drug for cancer therapy in combination with methotrexate.

Ocular Manifestations of Chikungunya Infection: A Systematic Review.

The Chikungunya virus (CHIKV) can cause long lasting symptoms and manifestations. However, there is little information on which ocular ones are most frequent following infection. We performed a systematic review (registered in the International Prospective Register of Systematic Reviews; no CRD42020171928) to establish the most frequent ocular manifestations of CHIKV infection and their associations with gender and age. Articles published until September 2020 were selected from PubMed, Scielo, Cochrane and Scopus databases. Only studies with CHIKV-infected patients and eye alterations were included. Reviews, descriptive studies, or those not investigating the human ocular manifestations of CHIKV, those with patients with other diseases and infections, abstracts and studies without relevant data were excluded. Twenty-five studies were selected for inclusion. Their risk of bias was evaluated by a modified Newcastle-Ottawa scale. The most frequent ocular symptoms of CHIKV infection included ocular pain, inflammation and reduced visual acuity, whilst conjunctivitis and optic neuritis were the most common manifestations of the disease. These occurred mostly in individuals of 42 ± 9.5 years of age and woman. The few available reports on CHIKV-induced eye manifestations highlight the need for further research in the field to gather more substantial evidence linking CHIKV infection, the eye and age/gender. Nonetheless, the data emphasizes that ocular alterations are meaningful occurrences of CHIKV infection which can substantially affect quality of life.

Polysaccharides from green sweet pepper increase the antineoplastic effect of methotrexate on mammary tumor cells.

This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg-1, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg-1 CAP (p.o.) + 1 mg kg-1 MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg-1, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity.

Evidence of a Role for the TRPC Subfamily in Mediating Oxidative Stress in Parkinson's Disease.

Parkinson's disease (PD) represents one of the most common multifactorial neurodegenerative disorders affecting the elderly population. It is associated with the aggregation of α-synuclein protein and the loss of dopaminergic neurons in the substantia nigra pars compacta of the brain. The disease is mainly represented by motor symptoms, such as resting tremors, postural instability, rigidity, and bradykinesia, that develop slowly over time. Parkinson's disease can also manifest as disturbances in non-motor functions. Although the pathology of PD has not yet been fully understood, it has been suggested that the disruption of the cellular redox status may contribute to cellular oxidative stress and, thus, to cell death. The generation of reactive oxygen species and reactive nitrogen intermediates, as well as the dysfunction of dopamine metabolism, play important roles in the degeneration of dopaminergic neurons. In this context, the transient receptor potential channel canonical (TRPC) sub-family plays an important role in neuronal degeneration. Additionally, PD gene products, including DJ-1, SNCA, UCH-L1, PINK-1, and Parkin, also interfere with mitochondrial function leading to reactive oxygen species production and dopaminergic neuronal vulnerability to oxidative stress. Herein, we discuss the interplay between these various biochemical and molecular events that ultimately lead to dopaminergic signaling disruption, highlighting the recently identified roles of TRPC in PD.