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1.
J Clin Invest ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833303

ABSTRACT

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8 T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8 T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce reactive oxygen species and ultimately increased the hypoxic state and granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.

2.
Cytotherapy ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38762805

ABSTRACT

BACKGROUND AIMS: Extracellular vesicles (EVs) represent a new axis of intercellular communication that can be harnessed for therapeutic purposes, as cell-free therapies. The clinical application of mesenchymal stromal cell (MSC)-derived EVs, however, is still in its infancy and faces many challenges. The heterogeneity inherent to MSCs, differences among donors, tissue sources, and variations in manufacturing conditions may influence the release of EVs and their cargo, thus potentially affecting the quality and consistency of the final product. We investigated the influence of cell culture and conditioned medium harvesting conditions on the physicochemical and proteomic profile of human umbilical cord MSC-derived EVs (hUCMSC-EVs) produced under current good manufacturing practice (cGMP) standards. We also evaluated the efficiency of the protocol in terms of yield, purity, productivity, and expression of surface markers, and assessed the biodistribution, toxicity and potential efficacy of hUCMSC-EVs in pre-clinical studies using the LPS-induced acute lung injury model. METHODS: hUCMSCs were isolated from a cord tissue, cultured, cryopreserved, and characterized at a cGMP facility. The conditioned medium was harvested at 24, 48, and 72 h after the addition of EV collection medium. Three conventional methods (nanoparticle tracking analysis, transmission electron microscopy, and nanoflow cytometry) and mass spectrometry were used to characterize hUCMSC-EVs. Safety (toxicity of single and repeated doses) and biodistribution were evaluated in naive mice after intravenous administration of the product. Efficacy was evaluated in an LPS-induced acute lung injury model. RESULTS: hUCMSC-EVs were successfully isolated using a cGMP-compliant protocol. Comparison of hUCMSC-EVs purified from multiple harvests revealed progressive EV productivity and slight changes in the proteomic profile, presenting higher homogeneity at later timepoints of conditioned medium harvesting. Pooled hUCMSC-EVs showed a non-toxic profile after single and repeated intravenous administration to naive mice. Biodistribution studies demonstrated a major concentration in liver, spleen and lungs. HUCMSC-EVs reduced lung damage and inflammation in a model of LPS-induced acute lung injury. CONCLUSIONS: hUCMSC-EVs were successfully obtained following a cGMP-compliant protocol, with consistent characteristics and pre-clinical safety profile, supporting their future clinical development as cell-free therapies.

3.
Pathogens ; 13(5)2024 May 16.
Article in English | MEDLINE | ID: mdl-38787268

ABSTRACT

Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p < 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis.

4.
Prev Vet Med ; 227: 106211, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38691954

ABSTRACT

Sporotrichosis is a widespread fungal infection that affects skin and subcutaneous tissues in humans and animals. In cats, it is displayed as nodules, ulcers and lesions on the nasal and respiratory mucosa. Antifungal treatment of cats is crucial but many cases are difficult, thus resulting in discontinue of the treatment, with disastrous consequences for the animal, encouraging contamination of the environment, other animals and people. The effects of responsible ownership education and health education for owners of cats with feline sporotrichosis as well as the interval between veterinary consultations on treatment outcomes for three groups of owners and their pet cats were evaluated in this study. The responsible ownership education and health education strategies consisted in videos in easy and accessible language for people with any level of education and were presented during consultations for two of the three groups included. The time between appointments was two weeks for two of the groups, and four weeks for one of the groups. The median of treatment time for the group without educational activities was 138 days, while for the other two groups it was 77.5 days and 86 days. It was found a significative reduction in the treatment time in the groups exposed to Responsible ownership education videos. There was no contamination of those responsible for home treatment, and the interval between monthly appointments did not impact on cure or death rates compared to the interval between fortnightly appointments. All these results can be applied to feline sporotrichoses treatment protocols increasing the owners treatment adherence and reducing either, the treatment discontinuation and the treatment costs and helps to control zoonotic sporotrichosis. The importance of attractive and comprehensible educational strategies as part of the feline sporotrichosis treatment protocol for the promotion of one health was highlighted.


Subject(s)
Cat Diseases , Health Education , Ownership , Sporotrichosis , Animals , Cats , Cat Diseases/therapy , Cat Diseases/prevention & control , Cat Diseases/microbiology , Sporotrichosis/veterinary , Sporotrichosis/drug therapy , Sporotrichosis/prevention & control , Sporotrichosis/therapy , Humans , Female , Male , Antifungal Agents/therapeutic use
5.
PLoS One ; 19(4): e0302317, 2024.
Article in English | MEDLINE | ID: mdl-38640135

ABSTRACT

Animal welfare encompasses the overall well-being of an animal, spanning both its physical and mental health, assessable through potential measurements. It stands in contrast to mistreatment, which involves actions, direct or indirect, that endanger an animal's well-being. This study sought to appraise the factors influencing the Brazilian population's understanding of dog welfare and mistreatment. The survey questions were adapted from the Animal Welfare Examination Protocol, utilized by veterinarians to evaluate suspected passive abuse cases in dogs. Out of 1377 responses, 1353 were valid and analyzed. Among the 19 assessed indicators, 15 demonstrated an adequate response rate surpassing 90% of all 1353 responses. However, for three questions related to comfort, a smaller yet notable percentage of responses were only minimally adequate. Moreover, in one question within the comfort assessment, 186 participants (13.74%) provided inadequate responses. This implies that these people could potentially subject animals to a state of low Animal Welfare. Lack of knowledge emerged as a potential root of passive abuse, specifically negligence. In the assessment of nutritional indicators, water supply and quality received unanimous adequate responses. In evaluating comfort perceptions, significant associations were noted between gender, dog ownership, family income, and responses regarding resting surface. Regarding health indicators, the majority responded appropriately. Female gender and dog ownership correlated with providing the appropriate response, while not owning a dog was associated with minimally adequate responses. In the context of comfort indicators, "Hitting the Dog" also demonstrated an association with gender, with females tending towards appropriate responses. Given the lack of significant correlation between educational levels and the most suitable responses, it underscores the urgency of implementing environmental education programs in schools with a focus on animal protection.


Subject(s)
Veterinarians , Animals , Humans , Dogs , Female , Brazil , Surveys and Questionnaires , Veterinarians/psychology , Educational Status , Animal Welfare , Perception
6.
Sci Rep ; 14(1): 8770, 2024 04 16.
Article in English | MEDLINE | ID: mdl-38627575

ABSTRACT

Oxygen availability can have profound effects on cell fate decisions and survival, in part by regulating expression of hypoxia-inducible factors (HIFs). In the ovary, HIF expression has been characterised in granulosa cells, however, any requirement in oocytes remains relatively undefined. Here we developed a Hif2a/Epas1 germline-specific knockout mouse line in which females were fertile, however produced 40% fewer pups than controls. No defects in follicle development were detected, and quality of MII oocytes was normal, as per assessments of viability, intracellular reactive oxygen species, and spindle parameters. However, a significant diminishment of the primordial follicle pool was evident in cKO females that was attributed to accelerated follicle loss from postnatal day 6 onwards, potentially via disruption of the autophagy pathway. These data demonstrate the importance of HIF signalling in oocytes, particularly at the primordial follicle stage, and lend to the importance of controlling oxygen tension in the development of in vitro growth and maturation approaches for assisted reproduction.


Subject(s)
Ovarian Follicle , Ovary , Animals , Female , Mice , Granulosa Cells/metabolism , Oocytes/metabolism , Ovarian Follicle/physiology , Oxygen/metabolism
7.
Epidemiol Serv Saude ; 33: e2023899, 2024.
Article in English, Portuguese | MEDLINE | ID: mdl-38629675

ABSTRACT

OBJECTIVE: To describe the profile of cases of mpox in the city of Rio de Janeiro between June and November 2022. METHODS: This was a descriptive study of secondary data obtained from mpox notification forms. Socioeconomic, clinical and spatial data were analyzed. RESULTS: Of the 928 cases, 93.7% were male, 85.0% cisgender male, 65.6% homosexual, 41.8% between 30 and 39 years old, and 41.0% were of White race/skin color. A total of 34.5% had immunosuppression due to illness, and 41.9% reported their HIV status as being positive. The most prevalent signs and symptoms were: skin lesions (96.6%), especially with multiple manifestations (67.8%) in the genital region (46.1%), in addition to fever (58.3%), adenomegaly (43.3%) and headache (38.7%). Most notifications occurred in public services (81.3%) and in hospital care (51.3%). CONCLUSION: The study revealed high incidence of mpox, especially among young, cisgender and homosexual men. Most cases were mild, with genital lesions, progressing to cure without hospitalization. Person-to-person transmission was predominant.


Subject(s)
Mpox (monkeypox) , Humans , Male , Adult , Female , Brazil/epidemiology , Cities , Incidence , Socioeconomic Factors
8.
Scand J Pain ; 24(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38557595

ABSTRACT

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.


Subject(s)
Fibromyalgia , Transcranial Direct Current Stimulation , Humans , Adult , Rats , Male , Animals , Transcranial Direct Current Stimulation/methods , Fibromyalgia/drug therapy , Pregabalin/pharmacology , Brain-Derived Neurotrophic Factor , Rats, Wistar , Tumor Necrosis Factor-alpha , Nociception/physiology , Reserpine , Pain , Anxiety/drug therapy , Biomarkers
9.
Eur J Radiol ; 173: 111396, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38428254

ABSTRACT

PURPOSE: To describe the structure of a dedicated body oncologic imaging fellowship program. To summarize the numbers and types of cross-sectional imaging examinations reported by fellows. METHODS: The curriculum, training methods, and assessment measures utilized in the program were reviewed and described. An educational retrospective analysis was conducted. Data on the number of examinations interpreted by fellows, breakdown of modalities, and examinations by disease management team (DMT) were collected. RESULTS: A total of 38 fellows completed the fellowship program during the study period. The median number of examinations reported per fellow was 2296 [interquartile range: 2148 - 2534], encompassing all oncology-relevant imaging modalities: CT 721 [646-786], MRI 1158 [1016-1309], ultrasound 256 [209-320] and PET/CT 176 [130-202]. The breakdown of examinations by DMT revealed variations in imaging patterns, with MRIs most frequently interpreted for genitourinary, musculoskeletal, and hepatobiliary cancers, and CTs most commonly for general staging or assessment of nonspecific symptoms. CONCLUSION: This descriptive analysis may serve as a foundation for the development of similar fellowship programs and the advancement of body oncologic imaging. The volume and diversity of examinations reported by fellows highlights the comprehensive nature of body oncologic imaging.


Subject(s)
Neoplasms , Positron Emission Tomography Computed Tomography , Humans , Retrospective Studies , Fellowships and Scholarships , Curriculum , Neoplasms/diagnostic imaging , Surveys and Questionnaires
10.
Parasit Vectors ; 17(1): 136, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38491527

ABSTRACT

BACKGROUND: Maintaining mosquito colonies in the laboratory requires a blood supply so that females' oocytes can mature and oviposition can take place. In this study, a new artificial hematophagy system for colonization and maintenance of Culex quinquefasciatus in the laboratory was developed and tested. METHODS: We developed an attractive polymeric biofilm including 25% L-lactic acid for use as a membrane in an artificial hematophagy system and compared the feeding rate of females with Parafilm-M®. We also evaluated the oviposition rate, larval survival and adult emergence of females fed through the attractive biofilm. RESULTS: The average percentage of female Cx. quinquefasciatus fed through the attractive biofilm was 87%, while only 20% became engorged with Parafilm-M® (p < 0.0001). Feeding through the attractive biofilm developed in this study produced high levels of evaluated biological parameters; the percentage of egg laying by females that underwent artificial hematophagy through the biofilm was 90%, with an average of 158 eggs per raft. From these eggs, 97% of the larvae hatched, of which 95% reached the pupal stage. The adult emergence rate corresponded to 93% of pupae. CONCLUSIONS: Insects fed with attractant through the biofilm system had a higher engorgement rate compared to those fed through Parafilm-M®. Our study is preliminary and suggests that polymeric biofilm has great potential for artificially feeding mosquitoes in the laboratory. Based on this research, new studies will be carried out with biofilm and different systems.


Subject(s)
Culex , Culicidae , Female , Animals , Paraffin , Ovum , Oviposition , Larva
11.
Vaccines (Basel) ; 12(3)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38543944

ABSTRACT

Immunization with various Leishmania species lacking centrin induces robust immunity against a homologous and heterologous virulent challenge, making centrin mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and Leishmania spp. lacking centrin are unable to replicate in vivo and are non-pathogenic. We developed a centrin-deficient Leishmania braziliensis (LbCen-/-) cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, LbCen-/- failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with LbCen-/- was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against L. braziliensis infection, distinct from L. major, L. donovani, and L mexicana centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with centrin-deficient L. donovani (LdonCen-/-) cross-protected against L. braziliensis challenge, illustrating the ability of LdonCen-/- to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while centrin deficiency in L. braziliensis causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response.

12.
J Mycol Med ; 34(2): 101473, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38493607

ABSTRACT

Diagnosis and management of fungal infections are challenging in both animals and humans, especially in immunologically weakened hosts. Due to its broad spectrum and safety profile when compared to other antifungals, itraconazole (ITZ) has been widely used in the treatment and prophylaxis of fungal infections, both in human and veterinary medicine. The dose and duration of management depend on factors such as the type of fungal pathogen, the site of infection, sensitivity to ITZ, chronic stages of the disease, the health status of the hosts, pharmacological interactions with other medications and the therapeutic protocol used. In veterinary practice, ITZ doses generally vary between 3 mg/kg and 50 mg/kg, once or twice a day. In humans, doses usually vary between 100 and 400 mg/day. As human and veterinary fungal infections are increasingly associated, and ITZ is one of the main medications used, this review addresses relevant aspects related to the use of this drug in both clinics, including case reports and different clinical aspects available in the literature.


Subject(s)
Antifungal Agents , Itraconazole , Mycoses , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Itraconazole/therapeutic use , Mycoses/drug therapy , Mycoses/veterinary , Mycoses/microbiology , Animals , Veterinary Medicine/methods
13.
J Affect Disord ; 355: 200-209, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38513773

ABSTRACT

INTRODUCTION: The impacts of antidepressant pharmacotherapies on cardiovascular risk are unclear. We completed a systematic review with meta-analysis to assess the effect of paroxetine on heart rate variability (HRV) in patients with major depressive disorder (MDD). METHODS: The searches were accomplished via EMBASE, MEDLINE/PubMed (using the National Library of Medicine), Cochrane Library, CINAHL, Scopus, and Web of Science databases. We included non-blind, single, or double-blind randomized control trials in patients older than 18 diagnosed with MDD. Paroxetine needs to be enforced as a chronic therapeutic medication. We included individual studies that investigated resting HRV. RESULTS: We documented 402 studies, only following screening and eligibility phases; only six were included (five studies in the meta-analysis). No significant change was noticed for the SDNN index: subtotal = 8.23 [CI: -2.17, 18.63], p = 0.12, I2 = 54 % (very low quality of evidence). A significant change was distinguished for the LF index: subtotal = 0.74 [CI: 0.33, 1.15], p = 0.0004, I2 = 0 % (low quality of evidence). A significant alteration was perceived for the HF index: subtotal = 0.33 [CI: 0.06, 0.6], p = 0.02, I2 = 0 % (low quality of evidence). CONCLUSION: Meta-analysis demonstrated that paroxetine could advance HRV in MDD patients. Nevertheless, our supposition is founded only on statistical analysis and the very low quality of evidence breakdown reinforces the necessity for further studies to confirm or reject this theory.


Subject(s)
Depressive Disorder, Major , Paroxetine , Humans , Paroxetine/adverse effects , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/chemically induced , Heart Rate , Double-Blind Method , Randomized Controlled Trials as Topic
14.
Clin Rehabil ; 38(5): 688-699, 2024 May.
Article in English | MEDLINE | ID: mdl-38347746

ABSTRACT

OBJECTIVE: There is a large gap between evidence-based recommendations for spatial neglect assessment and clinical practice in stroke rehabilitation. We aimed to describe factors that may contribute to this gap, clinician perceptions of an ideal assessment tool, and potential implementation strategies to change clinical practice in this area. DESIGN: Qualitative focus group investigation. Focus group questions were mapped to the Theoretical Domains Framework and asked participants to describe their experiences and perceptions of spatial neglect assessment. SETTING: Online stroke rehabilitation educational bootcamp. PARTICIPANTS: A sample of 23 occupational therapists, three physiotherapists, and one orthoptist that attended the bootcamp. INTERVENTION: Prior to their focus group, participants watched an hour-long educational session about spatial neglect. MAIN MEASURES: A deductive analysis with the Theoretical Domains Framework was used to describe perceived determinants of clinical spatial neglect assessment. An inductive thematic analysis was used to describe perceptions of an ideal assessment tool and practice-change strategies in this area. RESULTS: Participants reported that their choice of spatial neglect assessment was influenced by a belief that it would positively impact the function of people with stroke. However, a lack of knowledge about spatial neglect assessment appeared to drive low clinical use of standardised functional assessments. Participants recommended open-source online education involving a multidisciplinary team, with live-skill practice for the implementation of spatial neglect assessment tools. CONCLUSIONS: Our results suggest that clinicians prefer functional assessments of spatial neglect, but multiple factors such as knowledge, training, and policy change are required to enable their translation to clinical practice.


Subject(s)
Occupational Therapy , Perceptual Disorders , Stroke Rehabilitation , Stroke , Humans , Stroke Rehabilitation/methods , Stroke/complications , Stroke/diagnosis , Perceptual Disorders/diagnosis , Perceptual Disorders/etiology , Perceptual Disorders/rehabilitation , Occupational Therapists , Occupational Therapy/methods
15.
Rev Esc Enferm USP ; 57: e20230145, 2024.
Article in English, Portuguese | MEDLINE | ID: mdl-38362841

ABSTRACT

OBJECTIVE: To verify the association between prenatal care quality indicators and neonatal outcomes in maternity hospitals. METHOD: Hospital-based cross-sectional study in four high-risk referral maternity hospitals in the five health macro-regions enabled by the Stork Network in Ceará-Brazil. Between April 2017 and July 2018, 440 puerperal women were interviewed using simple probabilistic sampling and a formula with finite populations and stratification of each maternity hospital. The analysis involved Pearson's Chi-Square, Adjusted Residuals Analysis and Fisher's Exact. RESULTS: There was an association between fewer consultations with prematurity and low birth weight. Delivery in the maternity hospital where the woman lived was associated with low birth weight and the need for ventilatory support. CONCLUSION: Prenatal care quality indicators influenced neonatal outcomes, which underlines the importance of ensuring access and quality of care as ways of reducing infant morbidity and mortality.


Subject(s)
Hospitals, Maternity , Prenatal Care , Infant, Newborn , Pregnancy , Female , Humans , Cross-Sectional Studies , Postpartum Period , Infant, Premature , Brazil
16.
Neurobiol Learn Mem ; 209: 107902, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38336097

ABSTRACT

Calorie restriction (CR) is a non-invasive and economic approachknown to increase healthspan and life expectancy, through a decrease in oxidative stress, an increase in neurotrophins, among other benefits. However, it is not clear whether its benefit could be noted earlier, as at the beginning of middle-age. Hence, weaimed to determine whether six months of long-term CR, from early adulthood to the beginning of middle age (10 months of age) could positively affect cognitive, neurochemical, and behavioral parameters. Male C57BL6/J mice were randomly distributed into Young Control (YC, ad libitum food), Old Control (OC, ad libitum food), and Old Restricted (OR, 30 % of caloric restriction) groups. To analyze the cognitive and behavioral aspects, the novel object recognition task (NOR), open field, and elevated plus maze tests were performed. In addition, immunohistochemistry targetingΔFosB (neuronal activity), brain-derived neurotrophic factor (BDNF) and the DNA oxidative damage (8OHdG) in hippocampal subfields CA1, CA2, CA3, and dentate gyrus (DG), and in basolateral amygdala and striatum were performed. Our results showed that long-term CR prevented short-term memory impairment related to aging and increased 8OHdG in hippocampal DG. BDNF was not involved in the effects of either age or CR on memory at middle-age, as it increased in CA3 of the OC group but was not altered in OR. Regarding anxiety-type behavior, no parameter showed differences between the groups. In conclusion, while the effects of long-term CR on anxiety-type behavior were inconclusive, it mitigated the memory deficit related to aging, which was accompanied by an increase in hippocampal 8OHdG in DG. Future studies should investigate whether the benefits of CR would remain if the restriction were interrupted after this long-term protocol.


Subject(s)
Caloric Restriction , Oxidative Stress , Mice , Animals , Male , 8-Hydroxy-2'-Deoxyguanosine , Hippocampus/physiology , DNA , Memory Disorders/prevention & control , Dentate Gyrus
17.
Acta Trop ; 252: 107148, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38354996

ABSTRACT

Trypanosoma evansi is a flagellate protozoan that infects a wide range of hosts, especially horses. Clinically, the infection is characterized by rapid weight loss, anemia and mobility disorders. This study evaluated the efficacy of treatment gallium maltolate (GaM) in rats infected with T. evansi in the acute and chronic phases of the disease and its influence on the enzyme and blood parameters. 48 animals (Rattus norvegicus) were divided into 8 groups (A-H) of 6 animals each, namely: A: (negative control) uninfected; B: acutely infected positive control; C: chronically infected positive control; D: acutely infected, treated with GaM for 7 days post infection (p.i.); E: acutely infected treated with GaM for 3 days before infection (b.i) and 7 days p.i.; F: chronically infected, treated with GaM for 7 days p.i.; G: chronically infected, treated with GaM for 3 days b.i. and 7 days p.i.; and H: uninfected treated with GaM for 10 days. Acute infected animals (B, D and E) had a progressive increase in parasitemia and were died or euthanized before completing treatment days (5th days p.i.) as they had high parasitemia (over 100 field trypanosomes in the blood smear). Thus, it can be concluded that GaM was not effective against an acute infection. In untreated chronically infected animals (C) the parasitemia also increased progressively and they were euthanized on the 7th day p.i.. The chronically infected and treated animals (F and G) showed low parasitemia and after treatment became negative, showing no trypanosomes in the bloodstream until the 50th day of the experiment. Thus, we conclude that GaM was effective against chronic infections. In uninfected and treated animals (H) hematological, biochemical and enzymatic parameters had no significant changes when compared to the negative control group (A) demonstrating the low toxicity of GaM.


Subject(s)
Anemia , Organometallic Compounds , Pyrones , Trypanosoma , Trypanosomiasis , Mice , Rats , Horses , Animals , Trypanosomiasis/drug therapy , Trypanosomiasis/veterinary , Parasitemia/drug therapy
18.
Vet Parasitol Reg Stud Reports ; 47: 100962, 2024 01.
Article in English | MEDLINE | ID: mdl-38199700

ABSTRACT

This study reports the infection and diagnosis of the protozoan morphologic complex Trichomonas gallinae in a baby red-breasted toucan (Ramphastos dicolorus). Nodular lesions on the soft palate and edema in the oral cavity were observed macroscopically. Microscopically, a granuloma with multiple layers of necrosis interspersed with inflammatory polymorphonuclear infiltrates was observed. Parasitism was confirmed by parasitological diagnosis, isolation of the flagellates in culture medium, and Polymerase Chain Reaction (PCR) using 5.8S ribosomal RNA (rRNA). Flanking internal transcribed spacer (ITS) gene regions were amplified by polymerase chain reaction, and the sequences were analyzed phylogenetically using MEGA 11 software. Phylogenetic analysis based on ITS1/5.8S rRNA/ITS2 sequences demonstrated high nucleotide identity with two Trichomonas sequences available in GenBank, which were more closely related to T. vaginalis (99%) than to T. gallinae (98%). In addition to being potential transmitters of this protozoan, rigorous monitoring of infectious and parasitic diseases in wild bird populations is essential for their preservation. The forms of transmission of Trichomonas sp. favor the occurrence of the disease in many non-Columbiformes species, which is essential for the monitoring of this disease in wild birds.


Subject(s)
Trichomonas Infections , Trichomonas , Animals , Phylogeny , Trichomonas Infections/diagnosis , Trichomonas Infections/veterinary , Trichomonas/genetics , Birds , Databases, Nucleic Acid
19.
BMC Genomics ; 25(1): 14, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166730

ABSTRACT

BACKGROUND: Mapping expression quantitative trait loci (eQTLs) in skeletal muscle tissue in pigs is crucial for understanding the relationship between genetic variation and phenotypic expression of carcass traits in meat animals. Therefore, the primary objective of this study was to evaluate the impact of different sets of single nucleotide polymorphisms (SNP), including scenarios removing SNPs pruned for linkage disequilibrium (LD) and SNPs derived from SNP chip arrays and RNA-seq data from liver, brain, and skeletal muscle tissues, on the identification of eQTLs in the Longissimus lumborum tissue, associated with carcass and body composition traits in Large White pigs. The SNPs identified from muscle mRNA were combined with SNPs identified in the brain and liver tissue transcriptomes, as well as SNPs from the GGP Porcine 50 K SNP chip array. Cis- and trans-eQTLs were identified based on the skeletal muscle gene expression level, followed by functional genomic analyses and statistical associations with carcass and body composition traits in Large White pigs. RESULTS: The number of cis- and trans-eQTLs identified across different sets of SNPs (scenarios) ranged from 261 to 2,539 and from 29 to 13,721, respectively. Furthermore, 6,180 genes were modulated by eQTLs in at least one of the scenarios evaluated. The eQTLs identified were not significantly associated with carcass and body composition traits but were significantly enriched for many traits in the "Meat and Carcass" type QTL. The scenarios with the highest number of cis- (n = 304) and trans- (n = 5,993) modulated genes were the unpruned and LD-pruned SNP set scenarios identified from the muscle transcriptome. These genes include 84 transcription factor coding genes. CONCLUSIONS: After LD pruning, the set of SNPs identified based on the transcriptome of the skeletal muscle tissue of pigs resulted in the highest number of genes modulated by eQTLs. Most eQTLs are of the trans type and are associated with genes influencing complex traits in pigs, such as transcription factors and enhancers. Furthermore, the incorporation of SNPs from other genomic regions to the set of SNPs identified in the porcine skeletal muscle transcriptome contributed to the identification of eQTLs that had not been identified based on the porcine skeletal muscle transcriptome alone.


Subject(s)
Polymorphism, Single Nucleotide , Quantitative Trait Loci , Swine/genetics , Animals , Phenotype , Muscle, Skeletal/metabolism , Genome-Wide Association Study , Body Composition/genetics
20.
Exp Dermatol ; 33(1): e15008, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38284197

ABSTRACT

Skin is the ultimate barrier between body and environment and prevents water loss and penetration of pathogens and toxins. Internal and external stressors, such as ultraviolet radiation (UVR), can damage skin integrity and lead to disorders. Therefore, skin health and skin ageing are important concerns and increased research from cosmetic and pharmaceutical sectors aims to improve skin conditions and provide new anti-ageing treatments. Biomolecules, compared to low molecular weight drugs and cosmetic ingredients, can offer high levels of specificity. Topically applied enzymes have been investigated to treat the adverse effects of sunlight, pollution and other external agents. Enzymes, with a diverse range of targets, present potential for dermatological use such as antioxidant enzymes, proteases and repairing enzymes. In this review, we discuss enzymes for dermatological applications and the challenges associated in this growing field.


Subject(s)
Cosmetics , Skin Diseases , Humans , Ultraviolet Rays/adverse effects , Skin , Skin Diseases/therapy , Sunlight/adverse effects , Cosmetics/pharmacology
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