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1.
Transplant Direct ; 10(6): e1643, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769976

ABSTRACT

Background: The urinary microbiome, also known as the urobiome, was traditionally considered sterile. However, emerging evidence suggests its presence in the urinary tract. Urobiome dysbiosis has been associated with various urologic conditions, making it a topic of interest also in kidney transplantation. This systematic review examines the evidence of urobiome changes in kidney transplant recipients (KTRs). Methods: Systematic literature searches in the PubMed and SCOPUS databases. Results: Of the 770 articles identified, 8 met the inclusion criteria. The urobiome showed reduced diversity in KTRs compared with healthy controls and patients on dialysis. Proteobacteria enrichment was associated with graft stability or spontaneous tolerance in KTRs without immunological events. Kidney interstitial fibrosis and tubular atrophy were associated with changes in resident urinary microbes and increased pathogenic bacteria. Additionally, KTRs with chronic allograft dysfunction had a higher prevalence of Corynebacterium. Conclusions: The review highlights the importance of studying the urobiome in KTRs and its potential impact on transplant outcomes. The field remains largely unexplored, and further research is needed to establish consistent study designs and objectives. Future studies could lead to biomarker discovery, personalized therapies, and improved outcomes and graft survival in KTRs.

2.
Article in English | MEDLINE | ID: mdl-38688175

ABSTRACT

The present work aimed at the development and characterization of aroeira leaf flour (Schinus terebinthifolius Raddi), obtained by lyophilization and drying in an air circulation oven. The technological, physical, physico-chemical, morphological, functional, and microbiological aspects were analyzed. Physico-chemical analysis identified the following properties with values provided respectively for fresh leaves (FOin) and flours (FES and FLIO): low water activity (0.984, 0.370, 0.387 g/100 g), moisture (64.52, 5.37, 7.97 g /100 g), ash (2.69, 6.51, and 6.89 g/100 g), pH (0.89, 4.45, 4.48 g/100 g), lipids (0.84, 1.67, 5.23 g/100 g), protein (3.29, 8.23, 14.12 g/100 g), carbohydrates (17.02, 53.12, 33.02 g/100 g), ascorbic acid (19.70, 34.20, 36.90 mg/100 g). Sources of fiber from plant leaves and flours (11.64, 25.1, 32.89 g/100 g) showed increased levels of luminosity. For NMR, the presence of aliphatic and aromatic compounds with olefinic hydrogens and a derivative of gallic acid were detected. The most abundant minerals detected were potassium and calcium. Micrographs identified the presence of irregular, non-uniform, and sponge-like particles. The main sugars detected were: fructose, glucose, and maltose. Malic, succinic, citric, lactic, and formic acids were found. Fifteen phenolic compounds were identified in the samples, highlighting: kaempferol, catechin, and caffeic acid. The values ​​found for phenolics were (447, 716.66, 493.31 mg EAG/100 g), flavonoids (267.60, 267.60, 286.26 EC/100 g). Antioxidant activity was higher using the ABTS method rather than FRAP for analysis of FOin, FES, and FLIO. Since the flours of the aroeira leaf have an abundant matrix of nutrients with bioactive properties and antioxidant activity, they have a potential for technological and functional use when added to food.


Subject(s)
Anacardiaceae , Flour , Plant Leaves , Plant Leaves/chemistry , Anacardiaceae/chemistry , Flour/analysis , Freeze Drying , Carbohydrates/analysis , Carbohydrates/chemistry , Antioxidants/analysis , Antioxidants/chemistry , Schinus
3.
J Toxicol Environ Health A ; 87(11): 457-470, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38576186

ABSTRACT

Glutamate is one of the predominant excitatory neurotransmitters released from the central nervous system; however, at high concentrations, this substance may induce excitotoxicity. This phenomenon is involved in numerous neuropathologies. At present, clinically available pharmacotherapeutic agents to counteract glutamatergic excitotoxicity are not completely effective; therefore, research to develop novel compounds is necessary. In this study, the main objective was to determine the pharmacotherapeutic potential of the hydroalcoholic extract of Psidium guajava (PG) in a model of oxidative stress-induced by exposure to glutamate utilizing Danio rerio larvae (zebrafish) as a model. Data showed that treatment with glutamate produced a significant increase in oxidative stress, chromatin damage, apoptosis, and locomotor dysfunction. All these effects were attenuated by pre-treatment with the classical antioxidant N-acetylcysteine (NAC). Treatment with PG inhibited oxidative stress responsible for cellular damage induced by glutamate. However, exposure to PG failed to prevent glutamate-initiated locomotor damage. Our findings suggest that under conditions of oxidative stress, PG can be considered as a promising candidate for treatment of glutamatergic excitotoxicity and consequent neurodegenerative diseases.


Subject(s)
Psidium , Zebrafish , Animals , Glutamates/toxicity , Oxidative Stress , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Leaves
4.
Motor Control ; : 1-29, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580301

ABSTRACT

Premature life exposure, meaning an immature central nervous system, presents a significant challenge for the development of postural control and, in turn, overall motor development. Preventing motor delay thus requires identifying, characterizing, and quantifying deficit in postural control as early as possible. In our study, we reviewed the procedures used in past studies to assess postural control among individuals born preterm, specifically the characterization of participants, the instruments and motor tasks involved, the types of data collected and analyzed, and the outcomes. To that end, we performed a literature search on PubMed, Wiley Online Library, Web of Science, and Scopus using Boolean logic and assessed the quality of the studies with a standardized assessment based on the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Of 35 potential studies, 24 were included; all evaluated infants born preterm, but six did not include a control group of full-term infants. Although the heterogeneity of measurements, variability of instruments, and divergence in motor tasks examined limit definitive conclusions based on quantitative synthesis and the generalization of the results, most studies revealed dysfunctional postural control among individuals born preterm.

5.
Plants (Basel) ; 13(6)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38592872

ABSTRACT

The change in land use in the Brazilian Cerrado modifies the dynamics of soil organic matter (SOM) and, consequently, carbon (C) stocks and their fractions and soil enzyme activities. This study evaluated the effect of brachiaria (Brachiaria decumbens Stapf.) intercropped with Arabica coffee (Coffea arabica L.) on the stock and fractions of soil carbon and enzyme activities. The experiment was arranged in a completely randomized block design with three replications and treatments in a factorial design. The first factor consisted of coffee with or without intercropped brachiaria, the second of Arabica coffee cultivars ('I.P.R.103' and 'I.P.R.99') and the third factor of the point of soil sampling (under the canopy (UC) and in inter-rows (I)). Soil was sampled in layers of 0-10, 10-20, 20-30, 30-40, 40-60 and 60-80 cm. Soil from the 0-10 cm layer was also used to analyze enzymatic activity. Significant effects of coffee intercropped with brachiaria were confirmed for particulate organic carbon (POC), with highest contents in the 0-10 and 20-30 cm layers (9.62 and 6.48 g kg-1, respectively), and for soil enzymes (280.83 and 180.3 µg p-nitrophenol g-1 for arylsulfatase and ß-glucosidase, respectively).

6.
Int J Dev Neurosci ; 84(3): 163-176, 2024 May.
Article in English | MEDLINE | ID: mdl-38488315

ABSTRACT

INTRODUCTION: Recent research indicates that some brain structures show alterations in conditions such as Autism Spectrum Disorder (ASD). Among them, are the basal ganglia that are involved in motor, cognitive and behavioral neural circuits. OBJECTIVE: Review the literature that describes possible volumetric alterations in the basal ganglia of individuals with ASD and the impacts that these changes have on the severity of the condition. METHODOLOGY: This systematic review was registered in the design and reported according to the PRISMA Items and registered in PROSPERO (CRD42023394787). The study analyzed data from published clinical, case-contemplate, and cohort trials. The following databases were consulted: PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials, using the Medical Subject Titles (MeSH) "Autism Spectrum Disorder" and "Basal Ganglia". The last search was carried out on February 28, 2023. RESULTS: Thirty-five eligible articles were collected, analyzed, and grouped according to the levels of alterations. CONCLUSION: The present study showed important volumetric alterations in the basal ganglia in ASD. However, the examined studies have methodological weaknesses that do not allow generalization and correlation with ASD manifestations.


Subject(s)
Autism Spectrum Disorder , Basal Ganglia , Humans , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/pathology , Autism Spectrum Disorder/physiopathology , Basal Ganglia/pathology , Basal Ganglia/diagnostic imaging
7.
J Bras Pneumol ; 50(1): e20230233, 2024.
Article in English, Portuguese | MEDLINE | ID: mdl-38536982

ABSTRACT

Although lung cancer (LC) is one of the most common and lethal tumors, only 15% of patients are diagnosed at an early stage. Smoking is still responsible for more than 85% of cases. Lung cancer screening (LCS) with low-dose CT (LDCT) reduces LC-related mortality by 20%, and that reduction reaches 38% when LCS by LDCT is combined with smoking cessation. In the last decade, a number of countries have adopted population-based LCS as a public health recommendation. Albeit still incipient, discussion on this topic in Brazil is becoming increasingly broad and necessary. With the aim of increasing knowledge and stimulating debate on LCS, the Brazilian Society of Thoracic Surgery, the Brazilian Thoracic Association, and the Brazilian College of Radiology and Diagnostic Imaging convened a panel of experts to prepare recommendations for LCS in Brazil. The recommendations presented here were based on a narrative review of the literature, with an emphasis on large population-based studies, systematic reviews, and the recommendations of international guidelines, and were developed after extensive discussion by the panel of experts. The following topics were reviewed: reasons for screening; general considerations about smoking; epidemiology of LC; eligibility criteria; incidental findings; granulomatous lesions; probabilistic models; minimum requirements for LDCT; volumetric acquisition; risks of screening; minimum structure and role of the multidisciplinary team; practice according to the Lung CT Screening Reporting and Data System; costs versus benefits of screening; and future perspectives for LCS.


Subject(s)
Lung Neoplasms , Radiology , Thoracic Surgery , Humans , Lung Neoplasms/diagnosis , Brazil/epidemiology , Early Detection of Cancer/methods , Tomography, X-Ray Computed/methods , Mass Screening
8.
BJU Int ; 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520403

ABSTRACT

OBJECTIVE: This review investigates the prevalence of male non-neurogenic lower urinary tract symptoms (LUTS) after renal transplant, as kidney transplantation is a transformative intervention for patients with end-stage renal disease significantly enhancing quality of life that might be diminished by LUTS. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A systematic search in the PubMed and Scopus databases was performed using specific terms. Inclusion criteria considered male kidney transplant recipients, analysing outcomes in English-language studies. Discrepancies were resolved by consultation. RESULTS: Among 18 studies involving 29 086 recipients, the prevalence of non-neurogenic LUTS ranged from 5.8% to 33.0%. Studies predominantly used the International Prostate Symptom Score for evaluation. Surgical interventions, mostly for benign prostatic obstruction, ranged from 2.5% to 20.0%. Voiding and post-micturition symptoms were under-represented. CONCLUSION: This review found varied non-neurogenic LUTS prevalence and characteristics in male kidney transplant recipients, emphasising the need for standardised assessments, prospective studies, and improved understanding of LUTS mechanisms. Enhanced knowledge can guide interventions, additionally benefiting recipient quality of life.

9.
Bioorg Chem ; 146: 107302, 2024 May.
Article in English | MEDLINE | ID: mdl-38521010

ABSTRACT

Leishmaniasis, a group of neglected infectious diseases, encompasses a serious health concern, particularly with visceral leishmaniasis exhibiting potentially fatal outcomes. Nucleoside hydrolase (NH) has a fundamental role in the purine salvage pathway, crucial for Leishmania donovani survival, and presents a promising target for developing new drugs for visceral leishmaniasis treatment. In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs). The LdNH-IMER activity was monitored on-flow in a multidimensional liquid chromatography system, with the IMER in the first dimension. A C18 analytical column in the second dimension furnished the rapid separation of the substrate (inosine) and product (hypoxanthine), enabling direct enzyme activity monitoring through product quantification. LdNH-IMER exhibited high stability and was characterized by determining the Michaelis-Menten constant. A known inhibitor (1-(ß-d-Ribofuranosyl)-4-quinolone derivative) was used as a model to validate the established method in inhibitor recognition. Screening of three additional derivatives of 1-(ß-d-Ribofuranosyl)-4-quinolone led to the discovery of novel inhibitors, with compound 2a exhibiting superior inhibitory activity (Ki = 23.37 ± 3.64 µmol/L) compared to the employed model inhibitor. Docking and Molecular Dynamics studies provided crucial insights into inhibitor interactions at the enzyme active site, offering valuable information for developing new LdNH inhibitors. Therefore, this study presents a novel screening assay and contributes to the development of potent LdNH inhibitors.


Subject(s)
Leishmania donovani , Leishmaniasis, Visceral , Humans , N-Glycosyl Hydrolases/metabolism , Chromatography, Affinity , 4-Quinolones
10.
Nutrients ; 16(5)2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38474865

ABSTRACT

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.


Subject(s)
Extracellular Vesicles , Proteomics , Humans , Mice , Animals , Obesity/metabolism , Protein Processing, Post-Translational , Proteome/metabolism , Extracellular Vesicles/metabolism
11.
Chemosphere ; 352: 141423, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38340991

ABSTRACT

Chlorothalonil is a broad-spectrum organochlorine fungicide widely employed in agriculture to control fungal foliar diseases. This fungicide enters aquatic environments through the leaching process, leading to toxicity in non-target organisms. Organic contaminants can impact organism reproduction as they have the potential to interact with the neuroendocrine system. Although there are reports of toxic effects of chlorothalonil, information regarding its impact on reproduction is limited. The aim of the present study was to evaluate the influence of chlorothalonil on male reproductive physiology using the zebrafish (Danio rerio) as ecotoxicological model. Zebrafish were exposed for 7 days to two concentrations of chlorothalonil (0.1 and 10 µg/L) along with a control group (with DMSO - 0.001%). Gene expression of hypothalamus-pituitary-gonad axis components (gnrh2, gnrh3, lhr, fshr, star, hsd17b1, hsd17b3, and cyp19a1), as well as hepatic vitellogenin concentration were assessed. In sperm cells, reactive oxygen species (ROS) content, lipid peroxidation (LPO), mitochondrial functionality, and membrane integrity and fluidity were evaluated. Results indicate that exposure to the higher concentration of chlorothalonil led to a reduction in brain gnr2 expression. In gonads, mRNA levels of lhr, star, and hsd17b1 were decreased at both chlorothalonil concentrations tested. Similarly, hepatic vitellogenin concentration was reduced. Regarding sperm cells, a decreased ROS level was observed, without significant difference in LPO level. Additionally, a higher mitochondrial potential and lower membrane fluidity were observed in zebrafish exposed to chlorothalonil. These findings demonstrate that chlorothalonil acts as an endocrine disruptor, influencing reproductive control mechanisms, as evidenced by changes in expression of genes HPG axis, as well as hepatic vitellogenin concentration. Furthermore, our findings reveal that exposure to this contaminant may compromise the reproductive success of the species, as it affected sperm quality parameters.


Subject(s)
Endocrine Disruptors , Fungicides, Industrial , Nitriles , Water Pollutants, Chemical , Animals , Male , Zebrafish/metabolism , Endocrine Disruptors/metabolism , Hypothalamic-Pituitary-Gonadal Axis , Reactive Oxygen Species/metabolism , Fungicides, Industrial/metabolism , Vitellogenins/metabolism , Semen , Gonads , Spermatozoa/metabolism , Reproduction , Water Pollutants, Chemical/metabolism
12.
Biotechnol J ; 19(2): e2300325, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38385504

ABSTRACT

Ultraviolet (UV) radiation from sunlight can damage DNA, inducing mutagenesis and eventually leading to skin cancer. Topical sunscreens are used to avoid the effect of UV irradiation, but the topical application of DNA repair enzymes, such as photolyase, can provide active photoprotection by DNA recovery. Here we produced a recombinant Thermus thermophilus photolyase expressed in Escherichia coli, evaluated the kinetic parameters of bacterial growth and the kinetics and stability of the enzyme. The maximum biomass (𝑋𝑚𝑎𝑥 ) of 2.0 g L-1 was reached after 5 h of cultivation, corresponding to 𝑃X  = 0.4 g L-1 h. The µð‘šð‘Žð‘¥ corresponded to 1.0 h-1 . Photolyase was purified by affinity chromatography and high amounts of pure enzyme were obtained (3.25 mg L-1 of cultivation). Two different methods demonstrated the enzyme activity on DNA samples and very low enzyme concentrations, such as 15 µg mL-1 , already resulted in 90% of CPD photodamage removal. We also determined photolyase kM of 9.5 nM, confirming the potential of the enzyme at very low concentrations, and demonstrated conservation of enzyme activity after freezing (-20°C) and lyophilization. Therefore, we demonstrate T. thermophilus photolyase capacity of CPD damage repair and its potential as an active ingredient to be incorporated in dermatological products.


Subject(s)
Deoxyribodipyrimidine Photo-Lyase , Deoxyribodipyrimidine Photo-Lyase/genetics , Deoxyribodipyrimidine Photo-Lyase/chemistry , Deoxyribodipyrimidine Photo-Lyase/metabolism , Thermus thermophilus , Ultraviolet Rays , DNA/chemistry , DNA Repair
13.
J Mater Sci Mater Med ; 35(1): 12, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38315254

ABSTRACT

The development of wound dressings from biomaterials has been the subject of research due to their unique structural and functional characteristics. Proteins from animal origin, such as collagen and chitosan, act as promising materials for applications in injuries and chronic wounds, functioning as a repairing agent. This study aims to evaluate in vitro effects of scaffolds with different formulations containing bioactive compounds such as collagen, chitosan, N-acetylcysteine (NAC) and ε-poly-lysine (ε-PL). We manufactured a scaffold made of a collagen hydrogel bioconjugated with chitosan by crosslinking and addition of NAC and ε-PL. Cell viability was verified by resazurin and live/dead assays and the ultrastructure of biomaterials was evaluated by SEM. Antimicrobial sensitivity was assessed by antibiogram. The healing potential of the biomaterial was evaluated in vivo, in a model of healing of excisional wounds in mice. On the 7th day after the injury, the wounds and surrounding skin were processed for evaluation of biochemical and histological parameters associated with the inflammatory process. The results showed great cell viability and increase in porosity after crosslinking while antimicrobial action was observed in scaffolds containing NAC and ε-PL. Chitosan scaffolds bioconjugated with NAC/ε-PL showed improvement in tissue healing, with reduced lesion size and reduced inflammation. It is concluded that scaffolds crosslinked with chitosan-NAC-ε-PL have the desirable characteristics for tissue repair at low cost and could be considered promising biomaterials in the practice of regenerative medicine.


Subject(s)
Acetylcysteine , Anti-Infective Agents , Chitosan , Animals , Mice , Anti-Infective Agents/pharmacology , Biocompatible Materials/chemistry , Chitosan/chemistry , Collagen/chemistry , Tissue Scaffolds/chemistry , Wound Healing , Polylysine/chemistry
14.
Drug Chem Toxicol ; : 1-10, 2024 Feb 04.
Article in English | MEDLINE | ID: mdl-38311823

ABSTRACT

Polydatin (3,4',5-trihydroxystilbene-3-ß-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to its widespread adoption in human therapeutics and consumer products, a comprehensive investigation of its toxicological effects is crucial. In this study, the toxicity of polydatin was investigated in a developmental toxicity test using zebrafish (Danio rerio) as a valuable model for preclinical assessments. We employed the Fish Embryo Test (FET test - OECD n°236) to investigate the effects of polydatin on survival, hatchability, development, and behavior of zebrafish embryo-larval stage. Remarkably, the results demonstrated that polydatin up to 435 µM showed no toxicity. Throughout the exposure period, zebrafish embryos exposed to polydatin exhibited normal development, with no significant mortality observed. Furthermore, hatching success and heartbeat rate were unaffected, and no morphological abnormalities were identified, signifying a lack of teratogenic effects and cardiotoxicity. Locomotion activity assessment revealed normal swimming patterns and response to stimuli, indicating no neurotoxic effects. Our study provides valuable insights into the toxicological profile of polydatin, suggesting that it may offer potential therapeutic benefits under a considerable concentration range. In addition, zebrafish model proves to be an efficient system for early-stage toxicological screening, guiding further investigations into the secure utilization of polydatin for human health and wellness.

15.
Sci Rep ; 14(1): 2689, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38302481

ABSTRACT

Hepatic and pulmonary lesions are common in cetaceans, despite their poorly understood viral etiology. Herpesviruses (HV), adenoviruses (AdV) and hepatitis E virus (HEV) are emerging agents in cetaceans, associated with liver and/or pulmonary damage in mammals. We isolated and molecularly tested DNA for HV and AdV (n = 218 individuals; 187 liver and 108 lung samples) and RNA for HEV (n = 147 animals; 147 liver samples) from six cetacean families. All animals stranded or were bycaught in Brazil between 2001 and 2021. Positive-animals were analyzed by histopathology. Statistical analyses assessed if the prevalence of viral infection could be associated with the variables: species, family, habitat, region, sex, and age group. All samples were negative for AdV and HEV. Overall, 8.7% (19/218) of the cetaceans were HV-positive (4.8% [9/187] liver and 11.1% [12/108] lung), without HV-associated lesions. HV-prevalence was statistically significant higher in Pontoporiidae (19.2%, 10/52) when compared to Delphinidae (4.1%, 5/121), and in southeastern (17.1%, 13/76)-the most industrialized Brazilian region-when compared to the northeastern region (2.4%, 3/126). This study broadens the herpesvirus host range in cetaceans, including its description in pygmy sperm whales (Kogia breviceps) and humpback whales (Megaptera novaeangliae). Further studies must elucidate herpesvirus drivers in cetaceans.


Subject(s)
Adenoviridae Infections , Hepatitis E virus , Herpesviridae , Humpback Whale , Humans , Animals , Brazil/epidemiology , Adenoviridae/genetics , Herpesviridae/genetics , Adenoviridae Infections/epidemiology , Adenoviridae Infections/veterinary , Liver , Lung
16.
Nat Commun ; 15(1): 1633, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38395948

ABSTRACT

Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors of survival in melanoma. The MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant treatment with autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 patients collected serum and stool samples before and after 2 bimonthly injections to perform metabolomics (MB) and metagenomics (MG) as prespecified exploratory analysis. Clinical outcomes are reported separately. Here we show that different microbes were associated with prognosis, with the health-related Faecalibacterium prausnitzii standing out as the main beneficial taxon for no recurrence at 2 years (p = 0.008 at baseline, nDC arm). Therapy coincided with major MB perturbations (acylcarnitines, carboxylic and fatty acids). Despite randomization, nDC arm exhibited MG and MB bias at baseline: relative under-representation of F. prausnitzii, and perturbations of primary biliary acids (BA). F. prausnitzii anticorrelated with BA, medium- and long-chain acylcarnitines. Combined, these MG and MB biomarkers markedly determined prognosis. Altogether, the host-microbial interaction may play a role in localized melanoma. We value systematic MG and MB profiling in randomized trials to avoid baseline differences attributed to host-microbe interactions.


Subject(s)
Melanoma , Microbiota , Humans , Metabolic Reprogramming , Microbiota/genetics , Dendritic Cells
17.
PLoS Negl Trop Dis ; 18(1): e0011880, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38236929

ABSTRACT

The Lipid Droplet Protein Kinase (LDK) facilitates lipid droplet (LD) biogenesis, organelles involved in various metabolic and signaling functions in trypanosomatids. As LDK's function has not been previously explored in Leishmania spp., we utilized CRISPR/Cas9 technology to generate LDK-knockout lines of Leishmania infantum to investigate its role in this parasite. Our findings demonstrate that LDK is not an essential gene for L. infantum, as its deletion did not impede parasite survival. Furthermore, removing LDK did not impact the growth of promastigote forms of L. infantum lacking LDK. However, a noticeable reduction in LDs occurred during the stationary phase of parasite growth following LDK deletion. In the presence of myriocin, a LD inducer, LDK-knockout parasites displayed reduced LD abundance during both logarithmic and stationary growth phases compared to control parasites. Moreover, an infection analysis involving THP-1 cells revealed that 72 h post-infection, LDK-knockout L. infantum lines exhibited fewer infected macrophages and intracellular amastigotes than control parasites. LDK-knockout L. infantum lines also displayed 1.7 to 1.8 -fold greater resistance to trivalent antimony than control parasites. There were no observed alterations in susceptibility to amphotericin B, miltefosine, or menadione in LDK-knockout L. infantum lines. Our results suggest that LDK plays a crucial role in the biogenesis and/or maintenance of LDs in L. infantum, as well as in parasite infectivity and resistance to trivalent antimony.


Subject(s)
Leishmania infantum , Parasites , Parasitic Diseases , Animals , Leishmania infantum/physiology , Antimony/pharmacology , Lipid Droplets , Protein Kinases
18.
Prep Biochem Biotechnol ; 54(1): 1-11, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37071540

ABSTRACT

This study describes the production, characterization and application of an endoglucanase from Penicillium roqueforti using lignocellulosic agro-industrial wastes as the substrate during solid-state fermentation. The endoglucanase was generated after culturing with different agro-industrial wastes for 96 h without any pretreatment. The highest activity was obtained at 50 °C and pH 4.0. Additionally, the enzyme showed stability in the temperature and pH ranges of 40-80 °C and 4.0-5.0, respectively. The addition of Ca2+, Zn2+, Mg2+, and Cu2+ increased enzymatic activity. Halotolerance as a characteristic of the enzyme was confirmed when its activity increased by 35% on addition of 2 M NaCl. The endoglucanase saccharified sugarcane bagasse, coconut shell, wheat bran, cocoa fruit shell, and cocoa seed husk. The Box-Behnken design was employed to optimize fermentable sugar production by evaluating the following parameters: time, substrate, and enzyme concentration. Under ideal conditions, 253.19 mg/g of fermentable sugars were obtained following the saccharification of wheat bran, which is 41.5 times higher than that obtained without optimizing. This study presents a thermostable, halotolerant endoglucanase that is resistant to metal ions and organic solvents with the potential to be applied in producing fermentable sugars for manufacturing biofuels from agro-industrial wastes.


Subject(s)
Cellulase , Saccharum , Cellulase/chemistry , Cellulose , Dietary Fiber , Fermentation , Industrial Waste , Research Design , Saccharum/metabolism , Sugars , Calcium/chemistry , Copper/chemistry , Zinc/chemistry , Magnesium/chemistry
19.
Andrology ; 12(4): 835-840, 2024 May.
Article in English | MEDLINE | ID: mdl-37691298

ABSTRACT

BACKGROUND: Surgical exploration and closure of the tunica albuginea is the recommended treatment for penile fractures. The recovery of sexual function is the main result that surgeons and patients pursue. OBJECTIVE: We sought to evaluate the sexual health effects of a surgically corrected penile fracture. Secondarily, we sought to identify risk factors that may influence long-term sexual function and their effects on genital body image satisfaction. METHODS: A retrospective analysis of patients who underwent surgical correction of penile fractures between 2007 and 2022 in a tertiary center was performed. Lesion characteristics, weeks until the resumption of sexual activity, and post-operative sexual function were recorded. The presence of glans hypoesthesia, penile deformation, penile nodule palpation, and self-satisfaction with body image were assessed. RESULTS: Sixty-nine patients with a mean age of 42.30 ± 12.98 years and a median follow-up of 70 (20-134) months were identified. Sexual intercourse was recorded as a percentage. Penile deformation was the most common complication, appearing in 14.5% of patients, erectile dysfunction in 5.8%, penile nodules in 4.3%, and glans hypoesthesia in 2.9%. The median post-operative International Index of Erectile Function-5 was 24 (21.5-24). Self-satisfaction with body image had a median of 9 and was negatively associated with bilateral lesions and penile deformation. DISCUSSION AND CONCLUSION: Distal fractures could be linked to erectile dysfunction and glans hypoesthesia. Surgical correction of penile fractures shows positive functional and self-reported outcomes, and the potential andrological complications rarely necessitate specific treatment.


Subject(s)
Erectile Dysfunction , Penile Diseases , Male , Humans , Adult , Middle Aged , Erectile Dysfunction/etiology , Retrospective Studies , Hypesthesia/complications , Penis/surgery , Patient Satisfaction , Treatment Outcome
20.
Oral Oncol ; 148: 106623, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38006691

ABSTRACT

OBJECTIVES: Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis. MATERIALS AND METHODS: Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients. RESULTS: A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding. CONCLUSION: Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.


Subject(s)
Gastrointestinal Microbiome , Head and Neck Neoplasms , Mucositis , Male , Humans , Female , Squamous Cell Carcinoma of Head and Neck/complications , Head and Neck Neoplasms/complications , Mucositis/etiology , Prospective Studies , Chemoradiotherapy/adverse effects
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