Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of ...kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) on the testicular redox, as well as mediators of the unfolded protein response (UPR) in adult rats with hypothyroidism. Adult male Wistar rats were randomly separated into the Control (
= 15), Hypo (
= 13) and Hypo + Kp10 (
= 14) groups, and hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals received Kp10. Testis samples were collected for enzymatic, immunohistochemical and/or gene evaluation of mediators of oxidative stress (TBARs, lipid hydroperoxides (LOOH), ROS, peroxynitrite, SOD, CAT and GPX), endoplasmic reticulum stress (GRP78, ATF6, PERK, CHOP, HO-1 and sXBP1) and antiapoptocytes (BCL-2). Hypothyroidism increased apoptosis index, TBARS and LOOH concentrations, and reduced testicular gene expression of
,
and
, as well as the expression of
,
,
and
. Treatment with Kp10, in turn, reduced testicular apoptosis and the production of peroxynitrite, while increased SOD1 and GPX ½ expression, and enzymatic activity of CAT, but did not affect the lower expression of UPR mediators caused by hypothyroidism. This study demonstrated that hypothyroidism causes oxidative stress and dysregulated the UPR pathway in rat testes and that, although Kp10 does not influence the low expression of UPR mediators, it improves the testicular redox status, configuring it as an important antioxidant factor in situations of thyroid dysfunction.
Candida auris and Candida haemulonii are two emerging opportunistic pathogens that have caused an increase in clinical cases in the recent years worldwide. The differentiation of some Candida species ...is highly laborious, difficult, costly, and time-consuming depending on the similarity between the species. Thus, this study aimed to develop a new, faster, and less expensive methodology for differentiating between C . auris and C. haemulonii based on near-infrared (NIR) spectroscopy and multivariate analysis. C. auris CBS10913 and C. haemulonii CH02 were separated in 15 plates per species, and three isolated colonies of each plate were selected for Fourier transform near-infrared (FT-NIR) analysis, totaling 90 spectra. Subsequently, principal component analysis (PCA) and variable selection algorithms, including the successive projections algorithm (SPA) and genetic algorithm (GA) coupled with linear discriminant analysis (LDA), were employed to discern distinctive patterns among the samples. The use of PCA, SPA, and GA algorithms associated with LDA achieved 100% sensitivity and specificity for the discriminations. The SPA-LDA and GA-LDA algorithms were essential in selecting the variables (infrared wavelengths) of most importance for the models, which could be attributed to binding of cell wall structures such as polysaccharides, peptides, proteins, or molecules resulting from yeasts’ metabolism. These results show the high potential of combined FT-NIR and multivariate analysis techniques for the classification of Candida -like fungi, which can contribute to faster and more effective diagnosis and treatment of patients affected by these microorganisms.
Cryptococcus gattii is the main pathogen of cryptococcosis in healthy patients and is treated mainly with fluconazole and amphotericin B. The combination of these drugs has been questioned because ...the mechanisms of action could lead to a theoretical antagonistic interaction. We evaluated distinct parameters involved in the in vitro combination of fluconazole and amphotericin B against Cryptococcus gattii. Fourteen strains of C. gattii were used for the determination of MIC, fractional inhibitory concentration, time-kill curve, and postantifungal effect (PAFE). Ergosterol quantification was performed to evaluate the influence of ergosterol content on the interaction between these antifungals. Interaction between the drugs varied from synergistic to antagonistic depending on the strain and concentration tested. Increasing fluconazole levels were correlated with an antagonistic interaction. A total of 48 h was necessary for reducing the fungal viability in the presence of fluconazole, while 12 h were required for amphotericin B. When these antifungals were tested in combination, fluconazole impaired the amphotericin B activity. The ergosterol content decreased with the increase of fluconazole levels and it was correlated with the lower activity of amphotericin B. The PAFE found varied from 1 to 4 h for fluconazole and from 1 to 3 h for amphotericin B. The interaction of fluconazole and amphotericin B was concentration-dependent and special attention should be directed when these drugs are used in combination against C. gattii.
Acanthamoeba polyphaga mimivirus (APMV) is a giant virus from the Mimiviridae family. It has many unusual features, such as a pseudoicosahedral capsid that presents a starfish shape in one of its ...vertices, through which the ∼ 1.2-Mb double-stranded DNA is released. It also has a dense glycoprotein fibril layer covering the capsid that has not yet been functionally characterized. Here, we verified that although these structures are not essential for viral replication, they are truly necessary for viral adhesion to amoebae, its natural host. In the absence of fibrils, APMV had a significantly lower level of attachment to the Acanthamoeba castellanii surface. This adhesion is mediated by glycans, specifically, mannose and N-acetylglucosamine (a monomer of chitin and peptidoglycan), both of which are largely distributed in nature as structural components of several organisms. Indeed, APMV was able to attach to different organisms, such as Gram-positive bacteria, fungi, and arthropods, but not to Gram-negative bacteria. This prompted us to predict that (i) arthropods, mainly insects, might act as mimivirus dispersers and (ii) by attaching to other microorganisms, APMV could be ingested by amoebae, leading to the successful production of viral progeny. To date, this mechanism has never been described in the virosphere.
APMV is a giant virus that is both genetically and structurally complex. Its size is similar to that of small bacteria, and it replicates inside amoebae. The viral capsid is covered by a dense glycoprotein fibril layer, but its function has remained unknown, until now. We found that the fibrils are not essential for mimivirus replication but that they are truly necessary for viral adhesion to the cell surface. This interaction is mediated by glycans, mainly N-acetylglucosamine. We also verified that APMV is able to attach to bacteria, fungi, and arthropods. This indicates that insects might act as mimivirus dispersers and that adhesion to other microorganisms could facilitate viral ingestion by amoebae, a mechanism never before described in the virosphere.
Fungal infections vary from superficial to invasive and can be life-threatening in immunocompromised and healthy individuals. Antifungal resistance is one of the main reasons for an increasing ...concern about fungal infections as they become more complex and harder to treat. The fungal “omics” databases help us find drug resistance genes, which is of great importance and extremely necessary. With that in mind, we built a new platform for drug resistance genes. We added seven drug classes of resistance genes to our database: azoles (without specifying which drug), fluconazole, voriconazole, itraconazole, flucytosine, micafungin, and caspofungin. Species with known resistance genes were used to validate the results from our database. This study describes a list of 261 candidate genes related to antifungal resistance, with several genes displaying transport functions involved in azole resistance. Over 65% of the candidate genes found were related to at least one type of azole. Overall, the candidate genes found have functional annotations consistent with genes or enzymes that have been linked to antifungal resistance in previous studies. Also, candidate antifungal resistance genes found exhibit functional annotations consistent with previously described resistance mechanisms. The existence of an HMM profile focusing on antifungal resistance genes allows in silico searches for candidate genes, helping future wet lab experiments, and hence, reducing costs when studying candidate antifungal genes without prior knowledge of the species or genes. Finally, ResFungi has proven to be a powerful tool to narrow down candidate antifungal-related genes and unravel mechanisms related to resistance to help in the design of experiments focusing on the genetic basis of antifungal resistance.
Candida and Cryptococcus affect millions of people yearly, being responsible for a wide array of clinical presentations, including life‐threatening diseases. Interestingly, most human pathogenic ...yeasts are not restricted to the clinical setting, as they are also ubiquitous in the environment. Recent studies raise concern regarding the potential impact of agricultural use of azoles on resistance to medical antifungals in yeasts, as previously outlined with Aspergillus fumigatus. Thus, we undertook a narrative review of the literature and provide lines of evidence suggesting that an alternative, environmental route of azole resistance, may develop in pathogenic yeasts, in addition to patient route. However, it warrants sound evidence to support that pathogenic yeasts cross border between plants, animals and humans and that environmental reservoirs may contribute to azole resistance in Candida or other yeasts for humans. As these possibilities could concern public health, we propose a road map for future studies under the One Health perspective.
The aim of the present study was to analyze the reproductive aspects of the fat snook, Centropomus parallelus, in a tropical estuary. During the study period, 187 specimens were collected, including ...73 females and 114 males. The length at first sexual maturity was estimated to be 224 mm for the females and 141 mm for the males. An extensive reproductive period, January to August, was observed for the females based on the gonadosomatic index. For the males, the highest values were from July to October. Sexual segregation was observed in length classes, with predominance of males and females in the smaller and larger sizes, respectively. This pattern, observed in protandric hermaphrodites, has been confirmed with the identification of an individual in sexual transition. The average relative fecundity was 14,260 oocytes. The average absolute fecundity was 491,036 oocytes/female, and the average size of the vitellogenic oocytes was 435 µm. Management actions are suggested for better conservation of the species.
Atorvastatin as a promising anticryptococcal agent Ribeiro, Noelly de Queiroz; Costa, Marliete Carvalho; Magalhães, Thaís Furtado Ferreira ...
International journal of antimicrobial agents,
06/2017, Letnik:
49, Številka:
6
Journal Article
Recenzirano
Highlights • Drug repositioning is a fast and cheap strategy for the establishment of new antifungals. • Atorvastatin combined with fluconazole improved cryptococcosis caused by Cryptococcus gattii. ...• The polysaccharide capsule and fungal cell membrane are changed in the presence of statin. • These modifications induce death of C. gattii within phagocytes. • Mice treated with atorvastatin had increased survival and better clinical outcome.
Nasal leiomyosarcoma in a Quarter Horse Firmino, Millena de Oliveira; Alves, Rodrigo Cruz; Soares, Yanca Góes dos Santos ...
Ciência rural,
2023, Letnik:
53, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We described the clinical and anatomopathological findings observed in a case of nasal leiomyosarcoma in a five-year-old male Quarter Mile horse, whose main complaints were decreased sports ...performance and bilateral purulent nasal discharge. The nodule was observed in the nasal cavity, obstructing the left nostril and associated with purulent drainage. The nodule was of irregular shape and yellow color, measuring 19.4 cm × 6.9 cm × 4.3 cm in size, with coalescent multifocal areas that were brownish, friable, opaque, and fetid. When cut, the surface was compact, grayish-white, and smooth with yellow, friable, irregular multifocal areas, measuring 1-3.2 cm in diameter. Histopathological examination showed spindle-shaped neoplastic cells, which was negative on Masson’s trichromic stain. A diagnosis of leiomyosarcoma was established based on the morphotintorial aspects of neoplastic cells and confirmed through immunohistochemistry, with positive immunostaining for antibodies 1A4, HHF35, desmin, and S100. Leiomyosarcoma primarily affects the nasal cavity of horses and should be included in the differential diagnosis of diseases that affect the nasal cavity and cause nasal obstruction associated with dyspnea.
RESUMO: Descreve-se os achados clínicos e anatomopatológicos observados em um caso de leiomiossarcoma nasal em um equino, Quarto de Milha, macho, de cinco anos de idade, com queixa principal de diminuição do rendimento esportivo e secreção nasal purulenta bilateral. Na cavidade nasal, observou-se um nódulo obstruindo a narina esquerda associada à secreção purulenta. O nódulo era de superfície irregular, amarelada, brilhante, fibroelástica, medindo 19,4 x 6,9 x 4,3cm de tamanho, com áreas multifocais a coalescente acastanhadas, friáveis, opacas e fétidas. Ao corte, a superfície era compacta, branco-acinzentada e lisa com áreas multifocais amarelas, friáveis e irregulares, medindo 1-3,2 cm de diâmetro. No exame histopatológico foi observado proliferação de células neoplásicas fusiformes, que foram negativas na coloração de Tricrômico de Masson. O diagnóstico de leiomiossarcoma foi estabelecido com base nos aspectos morfotintoriais das células neoplásicas e confirmado através da imuno-histoquímica, no qual houve imunomarcação positiva para os anticorpos 1A4, HHF35, Desmina e S100. O leiomiossarcoma pode afetar primariamente a cavidade nasal de equinos, devendo ser incluído no diagnóstico diferencial de doenças que afetam a cavidade nasal e que provocam quadros de obstrução nasal associado a dispneia.
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