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Background Objective Methods Results Conclusion Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus.To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years.The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: “Candida glabrata”, “Nakaseomyces glabratus”, “Europe”, “resistance” and “Epidemiology” exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta‐analyses and book chapters.Fifty‐seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B.The number of candidemia cases associated with triazole‐resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Sporotrichosis is a fungal infection that can affect both humans and animals, caused by a species of thermo-dimorphic fungi of the genus Sporothrix. This pathology can be acquired by subcutaneous traumatic inoculation through contact with contaminated plants, soil or decomposing organic matter, and/or by inhalation of conidia. The infection can progress to chronic skin infection, or it can even spread to blood vessels, lymph, muscles, bones, and other organs, such as the lungs and nervous system. Those disseminated types are usually associated with cellular immunodeficiency and infection by inhalation, which explains why people living with human immunodeficiency virus (PLHIV) get infected in such a manner. This virus changes the natural history of sporotrichosis, producing a greater fungal load. Methods: The search was carried out in three databases: Pubmed, Scopus, and Scielo. Eligible articles were considered as those that described sporotrichosis in patients infected with HIV-AIDS, as well as case series. Results: A total of 24 articles were selected, with a sum of 37 patients with sporotrichosis and HIV infection. Of these patients, 31 came from Brazil, two from the United States, one from South Africa, one from Bangladesh, and two from an unspecified region. Regarding epidemiology, a predominance of the male sex was found in 28 of the 37 cases (75.6%), while nine were female (24.3%). Conclusions: Sporotrichosis infection continues to present in a more severe and disseminated way among HIV-positive subjects with lower CD4+ counts. [ABSTRACT FROM AUTHOR]

Background: Sporotrichosis is a fungal infection caused by species of the Sporothrix genus. Presently, the prevalence of sporotrichosis in the Americas is unknown, so this study aims to analyze the cases reported in the past 10 years. Methods: An advanced search was conducted from 2012 to 2022 in English and Spanish in PUBMED, SciELO, and Cochrane, with the terms: "sporotrichosis", "lymphocutaneous sporotrichosis", "fixed sporotrichosis", "mycosis", "Sporothrix spp.", "Sporothrix complex", "S. schenckii sensu stricto", "S. schenckii sensu lato", "S. globose", "S. brasiliensis", "S. luriei". Sporotrichosis is a fungal infection caused by species of the Sporothrix genus associated with "pathogenicity" or "epidemiology". Results: A total of 124 articles were found in the Americas, corresponding to 12,568 patients. Of these, 87.38% of cases were reported in South America, 11.62% in North America, and 1.00% in Central America and the Caribbean. Brazil, Peru, and Mexico had the highest number of cases. The most prevalent etiological agents were S. schenckii complex/Sporothrix spp. (52.91%), S. schenckii (42.38%), others (4.68%), and Not Determined (ND) (0.03%). The most frequent form of the disease was lymphocutaneous infection; however, the infection type was not determined in 5639 cases. Among the diagnostic methods, culture was the most used. Conclusions: There is a high occurrence of cases reported in the literature. South America is the region with the highest number of reports because of its environment (climate, inhalation of spores, etc.), zoonotic transmission (scratches and sneezes from contaminated animals), and possible traumatic inoculation due to outdoor activities (agriculture, gardening, and related occupations). Molecular diagnosis has not been sufficiently developed due to its high cost. [ABSTRACT FROM AUTHOR]

The physiopathologic characteristics of COVID-19 (high levels of inflammatory cytokines and T-cell reduction) promote fungal colonization and infection, which can go unnoticed because the symptoms in both diseases are very similar. The objective of this work was to study the current epidemiology of systemic mycosis in COVID-19 times. A literature search on the subject (January 2020–February 2021) was performed in PubMed, Embase, Cochrane Library, and LILACS without language restrictions. Demographic data, etiological agent, risk factors, diagnostic methods, antifungal treatment, and fatality rate were considered. Eighty nine publications were found on co-infection by COVID-19 and pneumocystosis, candidiasis, aspergillosis, mucormycosis, coccidioidomycosis, or histoplasmosis. In general, the co-infections occurred in males over the age of 40 with immunosuppression caused by various conditions. Several species were identified in candidiasis and aspergillosis co-infections. For diagnosis, diverse methods were used, from microbiological to molecular. Most patients received antifungals; however, the fatality rates were 11–100%. The latter may result because the clinical picture is usually attributed exclusively to SARS-CoV-2, preventing a clinical suspicion for mycosis. Diagnostic tests also have limitations beginning with sampling. Therefore, in the remainder of the pandemic, these diagnostic limitations must be overcome to achieve a better patient prognosis. [ABSTRACT FROM AUTHOR]

Hormone replacement therapy (HRT) increases the risk of endometrial and breast cancer. A strategy to reduce this incidence is the use of tibolone (TIB). The aim of this paper was to address the effects of TIB on the central nervous system (CNS). For the present review, MEDLINE (via PubMed), LILACS (via BIREME), Ovid Global Health, SCOPUS, Scielo, and PsycINFO (ProQuest Research Library) electronic databases were searched for the results of controlled clinical trials on peri- and postmenopausal women published from 1990 to September 2016. Also, this paper reviews experimental studies performed to analyze neuroprotective effects, cognitive deficits, neuroplasticity, oxidative stress, and stroke using TIB. Although there are few studies on the effect of this hormone in the CNS, it has been reported that TIB decreases lipid peroxidation levels and improves memory and learning. TIB has important neuroprotective effects that could prevent the risk of neurodegenerative diseases in postmenopausal women as well as the benefits of HRT in counteracting hot flashes, improving mood, and libido. Some reports have found that TIB delays cognitive impairment in various models of neuronal damage. It also modifies brain plasticity since it acts as an endocrine modulator regulating neurotransmitters, Tau phosphorylation, and decreasing neuronal death. Finally, its antioxidant effects have also been reported in different animal models. [ABSTRACT FROM AUTHOR]

A high performance liquid chromatography (HPLC) method for the estimation of pravastatin in human serum samples has been developed to monitor dyslipidemic patients. The method was fully validated and validation parameters were in the linearity range 10-200 ng/mL, correlation coefficient 0.99, mean recovery >0.73, quantification limit 10 ng/mL, and limit of detection, 5 ng/mL; this method was applied for pravastatin determination in human serum from Mexican dyslipidemic patients. Pravastatin values found for three studied patients were 73, 57, and <10 ng/mL, indicating the importance of monitoring, due to the metabolic variability of these chronic patients. [ABSTRACT FROM AUTHOR]

The present study analyses the clinical characteristics of patients diagnosed with cutaneous fusarium through a systematic review of cases reported in literature. A total of 39 cases were included, of which 53% were men, 30% were women, and in 17% the sex was not specified. The age ranged from 5 to 85 years. Most cases were reported in Brazil, followed by Japan and United States of America. The most common agent was Fusarium solani, in 37.5% of the patients. Most of the affected individuals had acute myeloid leukaemia and some of the predisposing factors, which included induction chemotherapy, febrile neutropenia, and bone marrow transplantation. The clinical topography of the lesions was located in 27.5% and disseminated in 72.5%, with the most observed clinical feature outstanding the presence of papules and nodules with central necrosis in 47% of the cases. Longer survival was demonstrated in those treated with more than three antifungals. It is concluded that cutaneous fusarium is a complex and challenging clinical entity, infection in patients with leukaemias underscores the need for thorough care to decrease morbidity and mortality. [ABSTRACT FROM AUTHOR]

Microsporum canis is a widely distributed dermatophyte, which is among the main etiological agents of dermatophytosis in humans and domestic animals. This fungus invades, colonizes and nourishes itself on the keratinized tissues of the host through various virulence factors. This review will bring together the known information about the mechanisms, enzymes and their associated genes relevant to the pathogenesis processes of the fungus and will provide an overview of those virulence factors that should be better studied to establish effective methods of prevention and control of the disease. Public databases using the MeSH terms "Microsporum canis", "virulence factors" and each individual virulence factor were reviewed to enlist a series of articles, from where only original works in English and Spanish that included relevant information on the subject were selected. Out of the 147 articles obtained in the review, 46 were selected that reported virulence factors for M. canis in a period between 1988 and 2023. The rest of the articles were discarded because they did not contain information on the topic (67), some were written in different languages (3), and others were repeated in two or more databases (24) or were not original articles (7). The main virulence factors in M. canis are keratinases, fungilisins and subtilisins. However, less commonly reported are biofilms or dipeptidylpeptidases, among others, which have been little researched because they vary in expression or activity between strains and are not considered essential for the infection and survival of the fungus. Although it is known that they are truly involved in resistance, infection and metabolism, we recognize that their study could strengthen the knowledge of the pathogenesis of M. canis with the aim of achieving effective treatments, as well as the prevention and control of infection. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) affects women more than men and consequently has been associated with menopause. Tibolone (TIB) has been used as a hormone replacement therapy to alleviate climacteric symptoms. Neuroprotective effects of TIB have also been reported in some animal models. Objective: This study aimed to assess the effect of TIB on memory and Aβ peptides and tau protein content in the hippocampus and cerebellum of transgenic 3xTgAD ovariectomized mice. Methods: Three-month-old female mice were ovariectomized. Ten days after surgery, animals were divided into four groups: wild-type (WT)+vehicle; WT+TIB (1 mg/kg); 3xTgAD+vehicle; and 3xTgAD+TIB (1 mg/kg). TIB was administered for three months, and memory was evaluated using the object-in-context recognition task. Subsequently, animals were decapitated, and the hippocampus and cerebellum were dissected. Using commercial ELISA kits, these brain structures were homogenized in a PBS buffer for quantifying Aβ40 and Aβ42 and phosphorylated and total tau. Results: A long-term memory deficit was observed in the 3xTgAD+vehicle group. In contrast, TIB treatment improved long-term memory in the 3xTgAD+TIB group than those treated with vehicle (p < 0.05). Furthermore, TIB treatment decreased Aβ and tau content in the hippocampus of 3xTgAD mice compared to vehicle-treated groups (p < 0.05). No significant changes were observed in the cerebellum. Conclusion: Chronic treatment with TIB showed neuroprotective effects and delayed AD neuropathology in the 3xTgAD mice. Our results support hormone replacement therapy with TIB in menopausal women for neuroprotection. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a set of risk factors that consist of abdominal obesity, arterial hypertension, alterations in the lipid profile, and hyperglycemia. The current therapeutic strategy includes polypharmacy, using three or more drugs to control each syndrome component. However, this approach has drawbacks that could lead to therapeutic failure. Multitarget drugs are molecules with the ability to act on different targets simultaneously and are an attractive alternative for treating complex diseases such as metabolic syndrome. Previously, we identified a triamide derivative of 5-aminoanthranilic acid that exhibited hypoglycemic, hypolipemic, and antihypertensive activities simultaneously. In the present study, we report the synthesis and in combo evaluation of new derivatives of anthranilic acid, intending to identify the primary structural factors that improve the activity over metabolic syndrome-related parameters. We found that substitution on position 5, incorporation of 3,4-dimethoxyphenyl substituents, and having a free carboxylic acid group lead to the in vitro inhibition of HMG-CoA reductase, and simultaneously the diminution of the serum levels of glucose, triglycerides, and cholesterol in a diet-induced in vivo model. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) causes memory deficit and alterations in other cognitive functions, mainly in adults over 60 years of age. As the diagnosis confirmation is performed by a postmortem neuropathological examination of the brain, this disease can be confused with other types of dementia at early stages. About 860,000 Mexicans are affected by dementia, most of them with insufficient access to adequate comprehensive health care services. Plasma biomarkers could be a rapid option for early diagnosis of the disease.Objective: This study aimed to analyze some plasma biomarkers (amyloid-β, tau, and lipids) in Mexican AD patients and control subjects with no associated neurodegenerative diseases.Methods: Plasma amyloid-β peptides (Aβ40 and Aβ42), total and phosphorylated tau protein (T-tau and P-tau), and cholesterol and triglyceride levels were quantified by enzyme-linked immunosorbent assay in AD patients and control subjects.Results: In Mexican AD patients, we found significantly lower levels of Aβ42 (p < 0.05) compared to the control group. In contrast, significantly higher levels of P-tau (p < 0.05) and triglycerides (p < 0.05) were observed in AD patients compared to controls. Furthermore, a significant correlation was found between the severity of dementia and plasma P-tau levels, Aβ42/Aβ40 and P-tau/T-tau ratios, and triglycerides concentrations. This correlation increased gradually with cognitive decline.Conclusion: The detection of these plasma biomarkers is an initial step in searching for a timely, less invasive, and cost-efficient diagnosis in Mexicans. [ABSTRACT FROM AUTHOR]

Introduction: Prolonged ozone exposure can produce a state of oxidative stress, which in turn causes alterations in the dynamics of the brain and affects memory and learning. Moreover, different investigations have shown that high flavonoid content berries show a great antioxidant activity. The relationship between the protective effect of the maqui berry extract and its antioxidant properties in the brain has not been studied in depth. Objectives: The present study evaluated whether the protection exerted by the aqueous extract of maqui berry in brain regions associated with cognitive performance is due to its antioxidant capacity. Methods: Sprague Dawley rats were exposed to 0.25 ppm ozone and administered with maqui berry extracts. At the end of the treatments, spatial learning and short- and long-term memory were evaluated, as well as oxidative stress markers. Results: The administration of 50 and 100 mg/kg of the aqueous extract of maqui berry was effective in preventing the cognitive deficit caused by chronic exposure to ozone. The antioxidant effect of the administration of maqui berry was analyzed in the prefrontal cortex, hippocampus, and amygdala. Oxidative stress markers levels decreased and the enzymatic activity of superoxide dismutase diminished in animals exposed to ozone treated with the 50 mg/kg dose of maqui berry. Discussion: These results show a relationship between protection at the cognitive level and a decrease in oxidative stress markers, which suggests that the prevention of cognitive damage is due to the antioxidant activity of the maqui berry. [ABSTRACT FROM AUTHOR]

The metabolic syndrome includes changes in blood glucose levels, arterial hypertension, triglycerides, dyslipidemia and central obesity. Countless reports have described the correlation between the metabolic syndrome and cognitive impairment. However, only a few reports have assessed cognitive impairment associated with the metabolic syndrome in animals of both sexes. For this purpose, Sprague‐Dawley male and female rats were fed either with a hypercaloric diet as model of the metabolic syndrome or with a standard chow diet as controls. Subsequently, spatial learning and memory (Morris water maze) as well as short‐ and long‐term memory (passive avoidance task) were evaluated. Body weight, blood pressure, triglycerides, and total cholesterol significantly increased (F(1, 36) = 94.89, p <.001) in rats fed with hypercaloric diet compared to control rats. Furthermore, cognitive impairment was observed in spatial learning and spatial memory on male rats but not on female rats fed with hypercaloric diet. In addition, a long‐term memory impairment was observed in both groups fed with hypercaloric diet in comparison to their respective control group (F(1, 32) = 10.61, p =.0027). Immunohistochemistry results showed no changes in the number of positive cells for NeuN, GFAP and Ox‐42. In males fed with a hypercaloric diet, a decrease in testosterone levels was observed, whereas estradiol levels decreased in females when compared with their respective control group (p <.0001). In this MetS animal model, metabolic and cognitive differences were observed in males and females, which demonstrates that sex hormones play a significant role in metabolic regulation and neuroprotection related to the CA1 region of the hippocampus. [ABSTRACT FROM AUTHOR]

Aging and neurodegenerative diseases share oxidative stress cell damage and depletion of endogenous antioxidants as mechanisms of injury, phenomena that are occurring at different rates in each process. Nevertheless, as the central nervous system (CNS) consists largely of lipids and has a poor catalase activity, a low amount of superoxide dismutase and is rich in iron, its cellular components are damaged easily by overproduction of free radicals in any of these physiological or pathological conditions. Thus, antioxidants are needed to prevent the formation and to oppose the free radicals damage to DNA, lipids, proteins, and other biomolecules. Due to endogenous antioxidant defenses are inadequate to prevent damage completely, different efforts have been undertaken in order to increase the use of natural antioxidants and to develop antioxidants that might ameliorate neural injury by oxidative stress. In this context, natural antioxidants like flavonoids (quercetin, curcumin, luteolin and catechins), magnolol and honokiol are showing to be the efficient inhibitors of the oxidative process and seem to be a better therapeutic option than the traditional ones (vitamins C and E, and β-carotene) in various models of aging and injury in vitro and in vivo conditions. Thus, the goal of the present review is to discuss the molecular basis, mechanisms of action, functions, and targets of flavonoids, magnolol, honokiol and traditional antioxidants with the aim of obtaining better results when they are prescribed on aging and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In recent years, a progressive increase in the incidence of invasive fungal infections (IFIs) caused by Candida glabrata has been observed. The objective of this literature review was to study the epidemiology, drug resistance, and virulence factors associated with the C. glabrata complex. For this purpose, a systematic review (January 2001–February 2021) was conducted on the PubMed, Scielo, and Cochrane search engines with the following terms: "C. glabrata complex (C. glabrata sensu stricto, C. nivariensis, C. bracarensis)" associated with "pathogenicity" or "epidemiology" or "antibiotics resistance" or "virulence factors" with language restrictions of English and Spanish. One hundred and ninety-nine articles were found during the search. Various mechanisms of drug resistance to azoles, polyenes, and echinocandins were found for the C. glabrata complex, depending on the geographical region. Among the mechanisms found are the overexpression of drug transporters, gene mutations that alter thermotolerance, the generation of hypervirulence due to increased adhesion factors, and modifications in vital enzymes that produce cell wall proteins that prevent the activity of drugs designed for its inhibition. In addition, it was observed that the C. glabrata complex has virulence factors such as the production of proteases, phospholipases, and hemolysins, and the formation of biofilms that allows the complex to evade the host immune response and generate fungal resistance. Because of this, the C. glabrata complex possesses a perfect pathogenetic combination for the invasion of the immunocompromised host. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a complex disease that affects almost a quarter of the world's adult population. In MetS, diabetes, obesity, hyperglycemia, high cholesterol, and high blood pressure are the most common disorders. Polypharmacy is the most used strategy for managing conditions related to MetS, but it has drawbacks such as low medication adherence. Multitarget ligands have been proposed as an interesting approach to developing drugs to treat complex diseases. However, suitable preclinical models that allow their evaluation in a context closer to a clinical situation of a complex disease are needed. From molecular docking studies, compound 1b, a 5-aminoanthranilic acid derivative substituted with 4′-trifluoromethylbenzylamino and 3′,4′-dimethoxybenzamide moieties, was identified as a potential multitarget drug, as it showed high in silico affinity against targets related to MetS, including PPAR-α, PPAR-γ, and HMG-CoA reductase. It was evaluated in a diet-induced MetS rat model and simultaneously lowered blood pressure, glucose, total cholesterol, and triglyceride levels after a 14-day treatment. No toxicity events were observed during an acute lethal dose evaluation test at 1500 mg/kg. Hence, the diet-induced MetS model is suitable for evaluating treatments for MetS, and compound 1b is an attractive starting point for developing multitarget drugs. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infects host cells by interacting its spike protein with surface angiotensin-converting enzyme 2 (ACE2) receptors, expressed in lung and other cell types. Although several risk factors could explain why some countries have lower incidence and fatality rates than others, environmental factors such as diet should be considered. It has been described that countries with high polyunsaturated fatty acid (PUFA) intake have a lower number of COVID-19 victims and a higher rate of recovery from the disease. Moreover, it was found that linoleic acid, an omega-6 PUFA, could stabilize the spike protein in a closed conformation, blocking its interaction with ACE2. These facts prompted us to perform in silico simulations to determine if other PUFA could also stabilize the closed conformation of spike protein and potentially lead to a reduction in SARS-CoV-2 infection. We found that: (a) countries whose source of omega-3 is from marine origin have lower fatality rates; and (b) like linoleic acid, omega-3 PUFA could also bind to the closed conformation of spike protein and therefore, could help reduce COVID-19 complications by reducing viral entrance to cells, in addition to their known anti-inflammatory effects. [ABSTRACT FROM AUTHOR]