Cytogenotoxic evaluation of the acetonitrile extract, citrinin and dicitrinin-A from Penicillium citrinum.

Endophytic fungi are promising sources of bioactive substances; however, their secondary metabolites are toxic to plants, animals, and humans. This study aimed toevaluate the toxic, cytotoxic, mutagenic and oxidant/antioxidant activities of acetonitrile extract (AEPc), citrinin (CIT) and dicitrinin-A (DIC-A) of Penicillium citrinum. For this, the test substances at 0.5; 1.0; 1.5 and 2 µg/mLwere exposed for 24 and 48 h in Artemia salina, and 48 h in Allium cepa test systems. The oxidant/antioxidant test was evaluated in pre-, co- and post-treatment with the stressor hydrogen peroxide (H2O2) in Saccharomyces cerevisiae. The results suggest that the AEPc, CIT and DIC-A at 0.5; 1.0; 1.5 and 2 µg/mL showed toxicity in A. saline, with LC50 (24 h) of 2.03 µg/mL, 1.71 µg/mL and 2.29 µg/mL, and LC50 (48 h) of 0.51 µg/mL, 0.54 µg/mL and 0.54 µg/mL, respectively.In A. cepa, the test substances also exerted cytotoxic and mutagenic effects. The AEPc, CIT and DIC-A at lower concentrations modulated the damage induced by H2O2 in the proficient and mutant strains of S. cerevisiae for cytoplasmic and mitochondrial superoxide dismutase. Moreover, the AEPc at 2 µg/mL and CIT at the two highest concentrations did not affect the H2O2-induced DNA damage in the test strains. In conclusion, AEPc, CIT and DIC-A of P. citrinum may exert their toxic, cytotoxic and mutagenic effects in the test systems possibly through oxidative stress induction pathway.

4-Dimethylaminoantipyrine as a Broad Electrochemical Indicator for Immunosensors Platform.

Here, we describe 4-dimethylaminoantipyrine (4-DMAA)-mediated interfacing as a broad biochemical indicator to stabilize and promote the higher response of electrodes for immunological detection. We hypothesized that the improved biological interactions of 4-DMAA with electrodes and biological samples may be due to the interaction properties of the benzene and pyrazole chemical groups with graphite and proteins, respectively. In order to demonstrate that 4-DMAA could be used as a general indicator in electrochemical immunoassays, we used peptides as probes for the diagnosis of four neglected tropical infectious diseases Tegumentary leishmaniasis, Visceral leishmaniasis, Strongyloidiasis, and Leprosy on commercial graphite screen-printed electrodes. 4-DMAA oxidation was used to indicate specific biological recognition between the epitope-based peptide and serum immunoglobulin G (IgG) from infected patients. We demonstrated that 4-DMAA should be incorporated into the electrodes prior to serum application, which avoids interference with its sensitivity and specificity. In addition, 4-DMAA oxidizes at a low anodic potential, and the oxidation peak is useful for detecting proteins in biological fluids. In summary, we have successfully demonstrated the broad application of 4-DMAA as a general indicator for the specific diagnosis of four infectious diseases in electrochemical immunosensors. Such a strategy is quite advantageous for indirect detection of proteins that lack electrochemical activities or are spatially inaccessible on the electrode surface. This new indicator opens a new avenue for monitoring biological recognition, especially for immunosensors.

Citrinin against breast cancer: A cytogenotoxicological study.

Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.

Antitumor effects of citrinin in an animal model of Sarcoma 180 via cytogenetic mechanisms.

Citrinin (CIT) is a cytotoxic, hepatotoxic, nephrotoxic and cardiotoxic metabolite obtained from Penicillium citrinum, that has been increasingly searched as an anticancer drug candidate. In this study, we assessed the antitumor effects of citrinin, using cytogenetic biomarkers for genotoxicity in Sarcoma 180 (S-180) ascitic fluid cells of mice. Citrinin, extracted from P. citrinum acetonitrile extract, was characterized by LC-MS. Cytotoxic assessment was done through using comet (alkaline version) and micronucleus assays. In S-180 cells, CI50 of CIT was 3.77 µg/mL, while at 12.5 and 100 µg/mL, CIT was as cytotoxic as doxorubicin (2 µg/mL). At 0.5, 1.0 and 2.0 µg/mL, it induced genotoxicity and mutagenicity in S-180 cells, especially at 2 µg/mL, triggering oxidative damage similar to hydrogen peroxide (10 mM). The antitumor effects were evidenced by a marked increase in S-180 cells apoptosis and necrosis due to clastogenic and/or aneugenic cytogenetic effects (micronucleus formation), as well as by induction of nucleoplasm bridges and nuclear buds, culminating in S-180 apoptosis and necrosis. CIT has potential as drug candidate for antitumor purposesbyinvolving cytogenetic mechanisms.

Role of Carotid Body in Intermittent Hypoxia-Related Hypertension.

Obstructive sleep apnea (OSA), a common breathing disorder, is recognized as an independent risk factor for systemic hypertension. Among the alterations induced by OSA, the chronic intermittent hypoxia (CIH) is considered the main factor for the hypertension. Exposure of rodents to CIH is the gold-standard method to study the mechanisms involved in the cardiovascular alterations induced by OSA. Although it is well known that CIH produces hypertension, the underlying mechanisms are not totally elucidated. It is likely that the CIH-induced systemic oxidative stress and inflammation may elicit endothelial dysfunction and increase the arterial blood pressure. In addition, OSA patients and animals exposed to CIH show sympathetic hyperactivity and potentiated cardiorespiratory responses to acute hypoxia, suggesting that CIH enhances the peripheral hypoxic chemoreflex. Recent experimental evidences support the proposal that CIH selectively enhances carotid body (CB) chemosensory reactivity to oxygen, which in turn increases sympathetic outflow leading to neurogenic hypertension. In this review, we will discuss the supporting evidence for a critical role of the CB in the generation and maintenance of the hypertension induced by CIH, also, the contribution of oxidative stress to enhance CB chemosensory drive and the activation of sympathetic-related centers in the brain.

Antigen production using heterologous expression of dengue virus-2 non-structural protein 1 (NS1) in Nicotiana tabacum (Havana) for immunodiagnostic purposes.

KEY MESSAGE: Expression of dengue-2 virus NS1 protein in Nicotiana tabacum plants for development of dengue immunodiagnostic kits. Dengue is one of the most important diseases caused by arboviruses in the world. A significant increase in its geographical distribution has been noticed over the last 20 years, with continuous transmission of several serotypes and emergence of the hemorrhagic fever in areas where the disease was previously not prevalent. Although the methodological processes for dengue diagnosis are in deep development and improvement, a limitation for the realization of dengue diagnostic tests is the difficulty of large-scale production of the antigen to be used in diagnostic tests. Due to this demand, the purpose of this study was to obtain the non-structural protein 1 (NS1) from dengue-2 serotype by heterologous expression in Nicotiana tabacum (Havana). After confirmation of the NS1 protein gene integration in the plant genome, the heterologous protein was characterized using SDS-PAGE and immunoblotting. In an immunoenzymatic test, the recombinant NS1 protein presents an antigen potential for development of dengue immunodiagnostic kits.

Association between polymorphism of interleukin-6 in the region -174G/C and tinnitus in the elderly with a history of occupational noise exposure.

UNLABELLED: Tinnitus is a symptom usually related to cochlear change that may arise from noise exposure and induces expression of proinflammatory cytokines including interleukin-6 (IL6). This study aimed to evaluate the association between the polymorphism of the IL6 gene in the region 174G/C and tinnitus in elderly with history of occupational noise exposure. SETTINGS AND DESIGN: This was a cross-sectional study with a sample of 179 independent elderly individuals aged >60 years. Information on exposure to occupational noise was obtained by interviews. Audiological evaluation was performed using pure tone audiometry and genotyped through polymerase chain reaction by restriction fragment length polymorphism (PCR-RFLP). Data were analyzed using the chi-square test and the odds ratio (OR), with the significance level set at 5%. Among the study subjects, 24.6% were homozygous for the G allele, 39.7% were homozygous for the C allele, and 35.8% were heterozygous for IL6 (P > 0.05). Of these, 33.5% reported noise exposure history, with 42.5% having tinnitus. We found significant association between the genotype and allele frequencies of the IL6 -174 gene (rs1800795) and tinnitus among the elderly with history of exposure to occupational noise (P = 0.03). The elderly with the C allele were less likely to have tinnitus associated with history of exposure to occupational noise [OR = 0.167, confidence interval (CI) 95% 0.167-0.749; P = 0.004] when compared to those carrying the G allele. This study suggests that there is an association between polymorphisms in the IL6 gene at region - 174G/C and susceptibility to tinnitus.

Uptake, translocation, and control of trumpet flower (Tecoma stans) with aminocyclopyrachlor.

To gain a better understanding of the physiology of the herbicide aminocyclopyrachlor in young plants of trumpet flower, the uptake and translocation were evaluated after the application of herbicide. This was determined by treating individual leaves with formulated herbicides plus (14)C-aminocyclopyrachlor after the application of the formulated herbicide. This experiment used a randomized experimental design with three replications. In addition, field studies were conducted to assess the effectiveness of foliar applications of aminocyclopyrachlor in association with metsulfuton-methyl. The plant absorbed 20% of the herbicide applied. The translocation percentage did not surpass 5% of the total amount applied. Only 1% of the herbicide applied was translocated to the roots. Rate of 40 + 13 g a.i. 100 L(-1) of aminocyclopyrachlor+metsulfuron-methyl was effective to control T. stans.

Interleukin-4 deficiency protects mice from acetaminophen-induced liver injury and inflammation by prevention of glutathione depletion.

OBJECTIVE: Interleukin-4 (IL-4) is a multifunctional cytokine involved in many diseases such as autoimmune hepatitis and idiosyncratic drug reactions. However, its role in acetaminophen (APAP)-induced liver injury remains unclear. Our objective was to evaluate the contribution of IL-4 to the pathogenesis of APAP-induced liver injury. METHODS: Balb/C (WT) and IL-4 knockout (IL-4(-/-)) mice were orally overdosed with APAP. After 24 h, survival percentage, biochemical and morphological markers of liver injury, and tissue inflammation were assessed. RESULTS: IL-4(-/-) mice were protected from APAP toxicity. Intravital confocal microscopy, tissue histology and serum ALT levels showed significantly less liver injury and inflammation than in the WT group, which may explain the increased survival rate of IL-4(-/-) mice. In addition, IL-4(-/-) mice had decreased production of tumor necrosis factor α, CXCL1 and interleukin-1ß in the liver, but not in a remote site such as the lungs. Hepatic macrophage activation was markedly reduced in IL-4-deficient mice. In addition, glutathione depletion-a primary cause of APAP-mediated injury-was significantly attenuated in IL-4(-/-) mice. CONCLUSIONS: Taken together, our data demonstrate that IL-4(-/-) mice are protected from APAP-induced liver injury due to reduced depletion of glutathione, which prevented liver damage and tissue inflammation.

Dengue immunoassay with an LSPR fiber optic sensor.

Dengue fever is a viral disease that affects millions of people worldwide. Specific tests for dengue are not usually performed due to high costs, complicated procedures and, in some cases, long time to yield a result. For widespread use of specific tests to be possible, fast, reliable and fairly simple methods are needed. In this paper, we present a new dengue diagnostic method for the acute phase of the infection. The method proposed uses an all-optical fiber sensor based on Localized Surface Plasmon Resonance (LSPR) and specular reflection from gold nanoparticles (AuNPs). Dengue anti-NS1 antibody was immobilized on AuNPs deposited on the endface of a standard multimode fiber (62.5 µm/125 µm). The sensor is able to detect NS1 antigen at different concentrations, with limit of quantification estimated to be 0.074 µg/ml = 1.54 nM. These results indicate that the sensor could potentially be used for dengue diagnosis in the acute phase of the infection.

Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles.

PURPOSE: Anti-oxidation and exocytosis are important for maintaining exocrine tissue homeostasis. During aging, functional and structural alterations occur in the lacrimal gland (LG), including oxidative damage to proteins, lipids, and DNA. The aims of the present study were to determine in the aging LG: a) the effects of aging on LG structure and secretory activity and b) changes in the expression of oxidative stress markers. METHODS: To address these goals, tear secretion composition and corneal impression cytology were compared between male Wistar rats of 2 (control) and 24 (aged) months. LG morphology and the expression levels of vitamin E and malonaldehyde (MDA) were evaluated to determine the anti-oxidant activity and lipid peroxidation, respectively. RT-PCR and western blot analysis were used for the analysis of Ras related in brain GTPase protein (Rab) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins of the secretory machinery (i.e.; Rab 3d, Rab 27, vesicle-associated membrane protein-2 (Vamp-2), and syntaxin). RESULTS: Histological analysis of aged rats revealed a higher frequency of corneal epithelia metaplasia. In the acinar cells, organelles underwent degeneration, and lipofucsin-like material accumulated in the cytoplasm along with declines in the anti-oxidant marker vitamin E. Rab3d and Rab27b mRNA levels fell along with Rab3d protein expression, whereas syntaxin levels increased. CONCLUSIONS: These findings indicate that exocytotic and anti-oxidant mechanisms become impaired with age in the rat LG. In parallel with these structural alterations, functional declines may contribute to the pathophysiology caused by tear film modification in dry eye disease.

Lacrimal Gland as a Target Organ for Adenovirus Gene Therapy Encoding Erythropoietin for Dry Eye Induced by Benzalkonium Chloride.

Purpose: The aims of this work were a) to describe the histology of the lacrimal gland (LG) and cornea induced by an adenovirus (Ad) vector encoding the human erythropoietin (Epo) gene delivered to the LG and b) to evaluate the therapeutic potential of this strategy to prevent benzalkonium chloride (BAK) corneal toxicity.Methods: Structure and function of male Wistar rats LG were compared in the groups: 1) naïve control and 2) Ad-hEpo in the right LG (RLG). The protective response against BAK eye drops was compared among the groups 1) naïve control, 2) BAK in the right eye, 3) Ad-hEpo RLG + BAK and 4) Ad-hEpo in the right salivary gland (RSG)+BAK. Ad-hEpo groups received an injection of AdLTR2EF1a-hEPO (25 ul, 1010 particles/ml) in the right LG or SG (positive control). The BAK groups received 0.2% BAK in the right cornea twice a day. The tests applied after 7 days, included tear secretion, hEPO mRNA detection by qRT-PCR, LG and cornea histology, LG ELISA for cytokines and hematocrit.Results: hEPO mRNA was present in the Ad-hEpo RLG and RSG, but not kidney or liver samples (negative controls). TNF-α and IL-1ß increased in the LG exposed to Ad-hEpo compared to naïve control (p = .0115 and p = .0397, respectively). BAK reduced tear secretion, but this reduction was prevented by Ad-hEpo RLG+BAK and Ad-hEpo RSG+BAK (p = .017). The corneal epithelia were thinner in the BAK-treated groups independent of Ad-hEpo (p = .0009). Hematocrit increased only in the Ad-hEpo RSG group (p = .01).Conclusions: Ad-hEpo infection of rat LG and SG induces local, but only the SG infection induced systemic changes in rats. Importantly, Ad-hEpo attenuated the BAK-mediated toxic reduction in tear flow. Future studies must consider viral vector tissue tropism, biodistribution and effective therapeutic gene products for ocular surface diseases.

Intra-host evolution during SARS-CoV-2 prolonged infection.

Long-term infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to virus dispersion and the control of coronavirus disease 2019 (COVID-19) pandemic. The reason why some people have prolonged infection and how the virus persists for so long are still not fully understood. Recent studies suggested that the accumulation of intra-host single nucleotide variants (iSNVs) over the course of the infection might play an important role in persistence as well as emergence of mutations of concern. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during prolonged infection. Thirty-three patients who remained reverse transcription polymerase chain reaction (RT-PCR) positive in the nasopharynx for on average 18 days from the symptoms onset were included in this study. Whole-genome sequences were obtained for each patient at two different time points. Phylogenetic, populational, and computational analyses of viral sequences were consistent with prolonged infection without evidence of coinfection in our cohort. We observed an elevated within-host genomic diversity at the second time point samples positively correlated with cycle threshold (Ct) values (lower viral load). Direct transmission was also confirmed in a small cluster of healthcare professionals that shared the same workplace by the presence of common iSNVs. A differential accumulation of missense variants between the time points was detected targeting crucial structural and non-structural proteins such as Spike and helicase. Interestingly, longitudinal acquisition of iSNVs in Spike protein coincided in many cases with SARS-CoV-2 reactive and predicted T cell epitopes. We observed a distinguishing pattern of mutations over the course of the infection mainly driven by increasing A→U and decreasing G→A signatures. G→A mutations may be associated with RNA-editing enzyme activities; therefore, the mutational profiles observed in our analysis were suggestive of innate immune mechanisms of the host cell defense. Therefore, we unveiled a dynamic and complex landscape of host and pathogen interaction during prolonged infection of SARS-CoV-2, suggesting that the host's innate immunity shapes the increase of intra-host diversity. Our findings may also shed light on possible mechanisms underlying the emergence and spread of new variants resistant to the host immune response as recently observed in COVID-19 pandemic.

Monitoring the bacterial community dynamics in a petroleum refinery wastewater membrane bioreactor fed with a high phenolic load.

The phenolic compounds are a major contaminant class often found in industrial wastewaters and the biological treatment is an alternative tool commonly employed for their removal. In this sense, monitoring microbial community dynamics is crucial for a successful wastewater treatment. This work aimed to monitor the structure and activity of the bacterial community during the operation of a laboratory-scale continuous submerged membrane bioreactor (SMBR), using PCR and RT-PCR followed by Denaturing Gradient Gel Electrophoresis (DGGE) and 16S rRNA libraries. Multivariate analyses carried out using DGGE profiles showed significant changes in the total and metabolically active dominant community members during the 4-week treatment period, explained mainly by phenol and ammonium input. Gene libraries were assembled using 16S rDNA and 16S rRNA PCR products from the fourth week of treatment. Sequencing and phylogenetic analyses of clones from 16S rDNA library revealed a high diversity of taxa for the total bacterial community, with predominance of Thauera genus (ca. 50%). On the other hand, a lower diversity was found for metabolically active bacteria, which were mostly represented by members of Betaproteobacteria (Thauera and Comamonas), suggesting that these groups have a relevant role in the phenol degradation during the final phase of the SMBR operation.

Colonization by Enterobacteriaceae is crucial for acute inflammatory responses in murine small intestine via regulation of corticosterone production.

Although dysbiosis in the gut microbiota is known to be involved in several inflammatory diseases, whether any specific bacterial taxa control host response to inflammatory stimuli is still elusive. Here, we hypothesized that dysbiotic indigenous taxa could be involved in modulating host response to inflammatory triggers. To test this hypothesis, we conducted experiments in germ-free (GF) mice and in mice colonized with dysbiotic taxa identified in conventional (CV) mice subjected to chemotherapy-induced mucositis. First, we report that the absence of microbiota decreased inflammation and damage in the small intestine after administration of the chemotherapeutic agent 5-fluorouracil (5-FU). Also, 5-FU induced a shift in CV microbiota resulting in higher amounts of Enterobacteriaceae, including E. coli, in feces and small intestine and tissue damage. Prevention of Enterobacteriaceae outgrowth by treating mice with ciprofloxacin resulted in diminished 5-FU-induced tissue damage, indicating that this bacterial group is necessary for 5-FU-induced inflammatory response. In addition, monocolonization of germ-free (GF) mice with E. coli led to reversal of the protective phenotype during 5-FU chemotherapy. E. coli monocolonization decreased the basal plasma corticosterone levels and blockade of glucocorticoid receptor in GF mice restored inflammation upon 5-FU treatment. In contrast, treatment of CV mice with ciprofloxacin, that presented reduction of Enterobacteriaceae and E. coli content, induced an increase in corticosterone levels. Altogether, these findings demonstrate that Enterobacteriaceae outgrowth during dysbiosis impacts inflammation and tissue injury in the small intestine. Importantly, indigenous Enterobacteriaceae modulates host production of the anti-inflammatory steroid corticosterone and, consequently, controls inflammatory responsiveness in mice.

Antitumoral effects of [6]-gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] in sarcoma 180 cells through cytogenetic mechanisms.

BACKGROUND: [6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice. METHODS: The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 µM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 µM) and hydrogen peroxide (85.33 µM) were used as positive controls. RESULTS: [6]-Gingerol, especially at concentrations of 42.66 and 85.33 µM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with H2O2 (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress. CONCLUSIONS: Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis.

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.

Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.

Possible Association between the Lack of Regular Physical Activity with Tinnitus and Headache: Cross-sectional Study.

Introduction Physical inactivity is an important risk factor for many aging-related symptoms. Studies suggest that physical activity may help to relieve tinnitus and headache. Objective To investigate the presence of tinnitus and headache in elderly individuals by associating it with the lack of regular physical activity. Methods A cross-sectional study including elderly individuals who live independently. The practice of physical activity and the complaints of headache and of tinnitus were checked by means of a questionnaire with objective questions. The statistical analysis was performed using the chi-squared test and relative risk, and a multiple logistic regression model was used to determine how well each factor predicted headache while controlling for each of the other factors. Results Based on a sample of 494 subjects, it was found that 213 (43.11%) complained of tinnitus. Among the complainants, 97 (45.53%) practiced physical activity regularly. We have confirmed associations between headache with lack of physical activity among elderly individuals with tinnitus ( p = 0.0440). It was also observed that certain factors, such as male gender and tinnitus, are independent factors for the complaint of headache. Conclusion We have found that headache could be a symptom related to the lack of regular physical activity among elderly individuals with tinnitus.

Antioxidant, anti-inflammatory and cytotoxic/antitumoral bioactives from the phylum Basidiomycota and their possible mechanisms of action.

Biologically active compounds from species of the phylum Basidiomycota have been shown a wide range of pharmacological activities and provide a vast reservoir of potential innovational drugs. The aim of this review is to discuss some mechanisms of action involved in antioxidant, anti-inflammatory and cytotoxic/antitumoral activities attributed to the bioactive compounds from species of the phylum Basidiomycota. We show that isolated compounds from extracts, secondary metabolites and polysaccharides that presented antioxidant properties have mechanisms of action involved in the elimination/capture of free radicals and reduction of lipid peroxidation. Also, some bioactives with anti-inflammatory activity were reported to enhance innate and cell-mediated immune responses. Finally, compounds that presented cytotoxic/antitumoral activity induces increased free radical production, collapse of the mitochondrial membrane potential and increased expression of proteins responsible for cell cycle arrest and apoptosis. Investigating the mechanisms of action of biologically active compounds will facilitate further efforts to accelerate the discovery of novel therapeutic strategies.