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1.
AMB Express ; 14(1): 82, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023846

ABSTRACT

Apis mellifera, crucial pollinators for both native and cultivated plants, also yield various products such as honey, wax, royal jelly, and propolis, extensively utilized in the food, pharmaceuticals, and cosmetics industries. Nosema ceranae, a prevalent microsporidian worldwide, stands as a significant pathogen for A. mellifera, showing resistance to conventional antibiotics. Consequently, the exploration of novel compounds for N. ceranae control becomes imperative. Dithiocarbimate derivatives emerge as promising antifungal candidates under evaluation for combating various pathogens, particularly those affecting plants. This study assessed the toxicity profile of six dithiocarbimate derivatives on A. mellifera worker survival and N. ceranae pathogen. Among these, four compounds exhibited minimal bee mortality and proceeded to further evaluation against N. ceranae. In vitro assays demonstrated their inhibitory effects on spore germination. Remarkably, the most potent compound suppressed N. ceranae spores by 62% at a concentration of 20 µmol L-1in vivo. Thus, these dithiocarbimate derivatives represent promising new antifungal agents for combatting nosemosis in honey bee populations.

2.
Discov Oncol ; 15(1): 171, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38761320

ABSTRACT

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system characterized by a clonal expansion of abnormal lymphocyte precursor cells. ALL is the most common form of cancer in children, but despite advances in treatment, it can still be fatal. Ethnic differences influence survival rates, and genomic ancestry plays an important role, especially in mixed-race populations such as Latin America. This study aims to analyze the influence of genomic ancestry on toxicity in children with ALL in the Amazon region. METHODS: The study included 171 patients (protocol number 119,649/2012-Ethics Committee) with ALL treated at a pediatric treatment center in Belém do Pará, in the Brazilian Amazon. The patients were submitted to the BFM protocol of induction therapy for ALL. Toxicity was assessed based on laboratory tests and adverse events, classified according to the CTC-NCI guide. Genomic ancestry was determined using autosomal informative markers. RESULTS: The majority of children (94.74%) developed some type of toxicity during treatment, 87.04% of which were severe. Infectious toxicity was the most common, present in 84.8% of cases, 77.24% of which were severe. Amerindian ancestry showed an association with the risk of severe general toxicity and severe infectious toxicity, with a contribution of 35.0% demonstrating a significant increase in risk. In addition, post-induction refractoriness and relapse were also associated with an increased risk of death. CONCLUSION: This study highlights the influence of Amerindian genomic ancestry on response to therapy and toxicity in children with ALL in the Amazon region. Understanding these associations can contribute to personalizing treatment and improving clinical outcomes.

3.
Int J Dent Hyg ; 2024 May 19.
Article in English | MEDLINE | ID: mdl-38764223

ABSTRACT

PURPOSES: Due to the popularity and increasing launch of toothpastes with whitening and sensitivity properties on the market, this study aimed to evaluate the fluoride concentrations in these products, since the concentrations of fluoride directly interfere with the anti-caries potential. METHODS: This is an experimental, in vitro study, where 37 samples from different batches (n = 3) purchased in different countries, were analysed in duplicate, via the ion-selective electrode technique to verify the concentration (µg/g or ppm F-) of total fluoride (TF), total soluble fluoride (TSF) and ionic fluoride (IF). For a comparative data analysis, ANOVA was applied followed by a Tukey's test for multiple comparisons. The level of confidence adopted was 95%. RESULTS: In the 37 assessed toothpastes, 45.9% contained NaF and 54.1% sodium monofluorophosphate (MFP). The TF found in the formulations ranged from 902.8 to 1539.4 ppm of F (mean: 1165.2 ± 179.3); fluoride concentration in the TSF fraction ranged from 708.8 to 1306.7 ppm of F (mean: 959.5 ± 162.4); IF results ranged from 101.9 to 1162.3 ppm of F (642.2 ± 294.1). Significant differences (p < 0.05) were found in the concentrations of the 59.5% assessed toothpastes in comparisons between declared and measured total fluoride (TF) concentrations, as well as in 62.2% when total fluoride (TF) and total soluble fluoride (TSF) were compared. CONCLUSIONS: In this study, most of the samples evaluated showed discrepancies when compared to the information declared by the manufacturers. In addition, the soluble concentrations found in half of the samples were lower than total concentrations and this may affect anti-caries effectiveness.

4.
Nitric Oxide ; 146: 48-57, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38579898

ABSTRACT

The highly porous morphology of chitosan cryogels, with submicrometric-sized pore cell walls, provides a large surface area which leads to fast water absorption and elevated swelling degrees. These characteristics are crucial for the applications of nitric oxide (NO) releasing biomaterials, in which the release of NO is triggered by the hydration of the material. In the present study, we report the development of chitosan cryogels (CS) with a porous structure of interconnected cells, with wall thicknesses in the range of 340-881 nm, capable of releasing NO triggered by the rapid hydration process. This property was obtained using an innovative strategy based on the functionalization of CS with two previously synthesized S-nitrosothiols: S-nitrosothioglycolic acid (TGA(SNO)) and S-nitrosomercaptosuccinic acid (MSA(SNO)). For this purpose, CS was previously methacrylated with glycidyl methacrylate and subsequently submitted to photocrosslinking and freeze-drying processes. The photocrosslinked hydrogels thus obtained were then functionalized with TGA(SNO) and MSA(SNO) in reactions mediated by carbodiimide. After functionalization, the hydrogels were frozen and freeze-dried to obtain porous S-nitrosated chitosan cryogels with high swelling capacities. Through chemiluminescence measurements, we demonstrated that CS-TGA(SNO) and CS-MSA(SNO) cryogels spontaneously release NO upon water absorption at rates of 3.34 × 10-2 nmol mg-1 min-1 and 1.27 × 10-1 nmol mg-1 min-1, respectively, opening new perspectives for the use of CS as a platform for localized NO delivery in biomedical applications.


Subject(s)
Chitosan , Cryogels , Nitric Oxide , Chitosan/chemistry , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Cryogels/chemistry , Porosity , Photochemical Processes , Cross-Linking Reagents/chemistry
5.
Genes (Basel) ; 15(2)2024 01 24.
Article in English | MEDLINE | ID: mdl-38397141

ABSTRACT

Reference genes are used as internal reaction controls for gene expression analysis, and for this reason, they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute leukemia patients, a panel of genes commonly used as endogenous controls was selected from the literature for stability analysis: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Abelson murine leukemia viral oncogene human homolog 1 (ABL), Hypoxanthine phosphoribosyl-transferase 1 (HPRT1), Ribosomal protein lateral stalk subunit P0 (RPLP0), ß-actin (ACTB) and TATA box binding protein (TBP). The stability of candidate reference genes was analyzed according to three statistical methods of assessment, namely, NormFinder, GeNorm and R software (version 4.0.3). From this study's analysis, it was possible to identify that the endogenous set composed of ACTB, ABL, TBP and RPLP0 demonstrated good performances and stable expressions between the analyzed groups. In addition to that, the GAPDH and HPRT genes could not be classified as good reference genes, considering that they presented a high standard deviation and great variability between groups, indicating low stability. Given these findings, this study suggests the main endogenous gene set for use as a control/reference for the gene expression in peripheral blood and bone marrow samples from patients with acute leukemias is composed of the ACTB, ABL, TBP and RPLP0 genes. Researchers may choose two to three of these housekeeping genes to perform data normalization.


Subject(s)
Gene Expression Profiling , Leukemia , Mice , Animals , Humans , Reverse Transcriptase Polymerase Chain Reaction , Genes, Essential , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Acute Disease , Leukemia/genetics , Gene Expression
6.
ACS Appl Mater Interfaces ; 15(42): 48930-48944, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37827196

ABSTRACT

An increasing number of studies have shown that the local release of nitric oxide (NO) from hydrogels stimulates tissue regeneration by modulating cell proliferation, angiogenesis, and inflammation. The potential biomedical uses of NO-releasing hydrogels can be expanded by enabling their application in a fluid state, followed by controlled gelation triggered by an external factor. In this study, we engineered a hydrogel composed of methacrylated hyaluronic acid (HAGMA) and thiolated gelatin (GELSH) with the capacity for in situ photo-cross-linking, coupled with localized NO release. To ensure a gradual and sustained NO release, we charged the hydrogels with poly(l-lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with S-nitrosoglutathione (GSNO), safeguarding SNO group integrity during photo-cross-linking. The formation of thiol-ene bonds via the reaction between GELSH's thiol groups and HAGMA's vinyl groups substantially accelerated gelation (by a factor of 6) and increased the elastic modulus of hydrated hydrogels (by 1.9-2.4 times). HAGMA/GELSH hydrogels consistently released NO over a 14 day duration, with the release of NO depending on the hydrogels' equilibrium swelling degree, determined by the GELSH-to-HAGMA ratio. Biocompatibility assessments confirmed the suitability of these hydrogels for biological applications as they display low cytotoxicity and stimulated fibroblast adhesion and proliferation. In conclusion, in situ photo-cross-linkable HAGMA/GELSH hydrogels, loaded with PLGA-GSNO nanoparticles, present a promising avenue for achieving localized and sustained NO delivery in tissue regeneration applications.


Subject(s)
Gelatin , Hyaluronic Acid , Hyaluronic Acid/chemistry , Gelatin/chemistry , Nitric Oxide , Hydrogels/pharmacology , Hydrogels/chemistry , Sulfhydryl Compounds/chemistry
7.
Eur J Phys Rehabil Med ; 59(6): 754-762, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37847246

ABSTRACT

BACKGROUND: Fibromyalgia is a syndrome characterized by generalized chronic pain and tenderness in specific areas. Photobiomodulation therapy (PBMT) using low-level laser therapy and/or light emitting diode therapy is an electrophysical agent that can be used alone or together with a static magnetic field (PBMT-sMF) to promote analgesia in several health conditions. Little evidence exists regarding the effects of using PBMT and PBMT-sMF in patients with fibromyalgia; this evidence is conflicting. AIM: We aimed to investigate the effects of using PBMT-sMF versus a placebo on reduction of the degree-of-pain rating, impact of fibromyalgia, pain intensity, and satisfaction with treatment in patients with fibromyalgia. DESIGN: A prospectively registered, monocentric, randomized placebo-controlled trial, with blinding of patients, therapists, and assessors, was performed. SETTING: The study was conducted at the Laboratory of Phototherapy and Innovative Technologies in Health (LaPIT) in Brazil, between March and October 2020. POPULATION: Ninety female patients with fibromyalgia were randomized to undergo either PBMT-sMF (N.=45) or placebo (N.=45) treatment. METHODS: Patients from both groups received nine treatment sessions, three times a week, for 3 weeks. Clinical outcomes were collected at baseline, the end of treatment, and at the follow-up appointment 4 weeks post-treatment. The primary outcome was the degree-of-pain rating, measured by the reduction of the tender point count. RESULTS: A decrease in the degree-of-pain rating was observed in patients allocated to the PBMT-sMF group, decreasing the number of tender points when compared to placebo group at the end of treatment (P<0.0001) and at the follow-up assessment (P<0.0001). Patients did not report any adverse events. CONCLUSIONS: PBMT-sMF is superior to placebo, supporting its use in patients with fibromyalgia. CLINICAL REHABILITATION IMPACT: PBMT-sMF might be considered an important adjuvant to the treatment regimens of patients with fibromyalgia.


Subject(s)
Chronic Pain , Fibromyalgia , Low-Level Light Therapy , Humans , Female , Fibromyalgia/radiotherapy , Clinical Protocols , Magnetic Fields
8.
Clinics (Sao Paulo) ; 78: 100243, 2023.
Article in English | MEDLINE | ID: mdl-37459671

ABSTRACT

AIMS: Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac ß1-Adrenergic (ß1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac ß1AR (isoproterenol, ISO), in the absence and presence of cardiac ß1AR (atenolol, AT) or A1R (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied. METHODS: PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 µg) in rat striatum. CIR was produced by a surgical interruption for 10 min followed by reestablishment of blood circulation in the descendent left coronary artery. On the incidence of CIR-Induced Ventricular Arrhythmias (VA), Atrioventricular Block (AVB), and Lethality (LET), evaluated by Electrocardiogram (ECG) analysis, the effects of intravenous treatment with ISO, AT and DPCPX (before CIR) were studied. RESULTS: VA, AVB and LET incidences were significantly higher in 6-OHDA (83%, 92%, 100%, respectively) than in control rats (58%, 67% and 67%, respectively). ISO treatment significantly reduced these incidences in 6-OHDA (33%, 33% and 42%, respectively) and control rats (25%, 25%, 33%, respectively), indicating that stimulation of cardiac ß1AR induced cardioprotection. This response was prevented by pretreatment with AT and DPCPX, confirming the involvement of cardiac ß1AR and A1R. CONCLUSION: Pharmacological modulation of cardiac ß1AR and A1R could be a potential therapeutic strategy to reduce severe arrhythmias and increase life expectancy in PD patients.


Subject(s)
Adrenergic Agents , Parkinson Disease , Rats , Animals , Adrenergic Agents/therapeutic use , Oxidopamine/therapeutic use , Arrhythmias, Cardiac/etiology , Receptors, Purinergic P1/therapeutic use
9.
J Forensic Sci ; 68(3): 780-789, 2023 May.
Article in English | MEDLINE | ID: mdl-36951355

ABSTRACT

Currently, SEM-EDS is used to detect gunshot residue (GSR) from the presence of Ba, Pb, and Sb in the sample. However, the development of new nontoxic ammunition (NTA) has prevented conventional metals from being found. In this work, we aim to determine the presence of an inorganic luminescent chemical marker based on rare earth in gunshot residues using the technique of squarewave voltammetry (SWV). After firing, the luminescent complex [(Eu2 Zr)(btc)3 (Hbtc)0.5 .6H2 O], which is used as a chemical marker, can be detected under a UV lamp. An aqueous solution with 0.1 mol L-1 KCl as supporting electrolyte can be easily collected on carbon paste electrode surfaces for SWV analysis A = 100 mV, f = 10 Hz, and step potential of 5 mV are required. The luminescent marker incorporated into the carbon paste electrode showed two anodic peak currents in the region of 0.4 V (vs Ag/AgCl) and at 0.75 V (vs Ag/AgCl) and also a cathodic one in 0.4 V (vs Ag/AgCl). SEM-EDS was able to analyze the same voltammetric results for conventional and nontoxic ammunition containing the luminescent marker. Therefore, voltammetry and SEM-EDS are valid for detecting the new residue marker in GSR. Despite this, the electrochemical method is still more advantageous because of its low cost and lack of expensive equipment and supplies in forensic laboratories.

10.
Phys Chem Chem Phys ; 25(3): 1903-1922, 2023 Jan 18.
Article in English | MEDLINE | ID: mdl-36541431

ABSTRACT

The application of various density functional approximations (DFAs) and an emphasis on popular methods without any consensus have prevailed in computational studies dedicated to carbocations. More importantly, an extensive and rigorous benchmark investigation on density functionals for the class is still lacking. To close this gap, we present a comprehensive benchmark study of quantum chemical methods on a series of classical and nonclassical carbocations, the CARBO33 dataset. We evaluate a total of 107 DFT methods from all rungs giving particular attention to double hybrid density functionals as the potential of the class has been largely undermined in the context of carbocations. To support our findings, DLPNO-CCSD(T) at the complete basis set (CBS) limit and W1-F12 are used as reference methods. Our results indicate that the composite CBS-QB3 method performs poorly and should not be adopted for target energies. Oftentimes, the tested DFAs of a lower rung perform better than several DFAs in a higher rung of Perdew's "Jacob's ladder". Nonetheless, double hybrids DSD-PBEP86-NL and ωB97X-2-D3(BJ) stand out by showing the overall best performance. Among the hybrids evaluated, about half of them show mean absolute deviation (MAD) below 1.1 kcal mol-1, including the popular hybrids M06-2X and mPW1PW91. In this family, MN15-D3(BJ) performs particularly well (MAD = 0.77 kcal mol-1) displaying reliable results across various tests. Highly popular B3LYP exhibited one of the worst performances (MAD = 4.74 kcal mol-1), and we do not recommend its application to carbocations. We also assess the 24 general-purpose basis sets of single- up to quadruple-ζ quality. The best compromise between accuracy and computational cost is achieved with cc-pVTZ followed by def2-TZVP. Computations on larger structures of general interest, including terpene carbocations, are also presented for selected DFT methods confirming general trends in the results.

11.
Macromol Biosci ; 23(3): e2200448, 2023 03.
Article in English | MEDLINE | ID: mdl-36519642

ABSTRACT

The design of bioresorbable vascular stents (BVS) capable of releasing nitric oxide (NO) at the implant site may enable BVS to mimic the antiplatelet, antiproliferative, and pro-endothelial actions of NO, overcoming complications of BVS such as late thrombosis and restenosis. In this study, the fabrication of BVS composed of methacrylated poly(dodecanediol citrate-co-dodecanediol S-nitroso-mercaptosuccinate) (mP(DC-co-DMSNO)), a novel elastomeric, bioabsorbable, and photocurable copolyester, containing covalently bound S-nitrosothiol groups in the carbon backbone of the polymer, is reported. The mP(DC-co-DMSNO) stents are manufactured via photoinduced 3D printing and allow deployment via a self-expansion process from a balloon catheter. After deployment, hydration of the stents triggers the release of NO, which is maintained during the slow hydrolysis of the polymer. Real-time NO release measurements show that by varying the copolyester composition and the strut geometry of the mP(DC-co-DMSNO) stents, it is possible to modulate their NO release rate in the range of 30-52 pmol min-1 cm-2 . Preliminary biological assays in cell culture show that endothelial cells adhere to the surface of the stents and that NO release favors their endothelization. Thus, mP(DC-co-DMSNO) may emerge as a new platform for the fabrication of advanced BVS.


Subject(s)
Absorbable Implants , Drug-Eluting Stents , Nitric Oxide , Endothelial Cells , Treatment Outcome , Stents , Printing, Three-Dimensional , Polymers
13.
Phys Rev E ; 106(2-1): 024302, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36109937

ABSTRACT

A simple model to study cooperation is the two-species symbiotic contact process (2SCP), in which two different species spread on a graph and interact by a reduced death rate if both occupy the same vertex, representing a symbiotic interaction. The 2SCP is known to exhibit a complex behavior with a rich phase diagram, including continuous and discontinuous transitions between the active phase and extinction. In this work, we advance the understanding of the phase transition of the 2SCP on uncorrelated networks by developing a heterogeneous mean-field (HMF) theory, in which the heterogeneity of contacts is explicitly reckoned. The HMF theory for networks with power-law degree distribution shows that the region of bistability (active and inactive phases) in the phase diagram shrinks as the heterogeneity level is increased by reducing the degree exponent. Finite-size analysis reveals a complex behavior where a pseudodiscontinuous transition at a finite size can be converted into a continuous one in the thermodynamic limit, depending on degree exponent and symbiotic coupling. The theoretical results are supported by extensive numerical simulations.

14.
Clin Oral Investig ; 26(11): 6829-6837, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35930141

ABSTRACT

AIM: This study aimed to identify medications taken by patients before dental appointments and to simulate and characterize their interactions with medications often prescribed by dental surgeons. MATERIALS AND METHODS: A retrospective cross-sectional study evaluated 320 medical records, 118 from the Emergency Service (ES) archives, and 202 from elective appointments at the Dental Clinic (DC) of a university in southern Brazil. Drug interactions were identified and classified according to severity using the Medscape® application into four grades: (1) Minor, (2) Monitor closely, (3) Serious, or (4) Contraindicated. Descriptive and inferential statistical analyses were carried out (α = 5%). RESULTS: Preexisting systemic conditions were noted in 55.9% of the medical records from the ES and 64.35% from the DC. In the ES records, 47.45% contained information on continuous use medication for treatment of systemic conditions and 59.40% of DC records contained such information. A total of 359 potential interactions were found. Drug interactions with analgesics were most frequent, accounting for 50.41% of the sample. CONCLUSIONS: The most prevalent drug interaction severity was grade 2: monitor or use with caution. Many patients take medications to treat systemic conditions and seek dental care, generating a significant possible source of drug interactions. CLINICAL RELEVANCE: Prescribers must carefully analyze the patients' medical histories and obtain accurate data regarding their use of medications to be able to assess the risk-benefit relationships of possible combinations.


Subject(s)
Dentistry , Drug Prescriptions , Humans , Cross-Sectional Studies , Retrospective Studies , Drug Interactions
15.
Pest Manag Sci ; 78(11): 4741-4752, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35871604

ABSTRACT

BACKGROUND: The purpose of this work was to investigate the potential use of zinc-dithiocarbimate salts to control Hemileia vastatrix, the causal agent of the coffee leaf rust disease, and to evaluate their toxicity towards Apis mellifera, one of the most important coffee plant pollinators. RESULTS: Zinc-dithiocarbimate salts were prepared and fully characterized by infrared, proton (1 H) and carbon-13 (13 C) nuclear magnetic resonance and elemental analyses of carbon (C), hydrogen (H), nitrogen (N) and zinc (Zn). X-ray diffraction technique studies confirmed the proposed structures. The salts inhibited the germination of H. vastatrix spores in vitro, with a 50% inhibitory concentration (IC50 ) from 12 to 18 µmol.L-1 and a 90% inhibitory concentration (IC90 ) from 23 to 26 µmol.L-1 . Zinc-dithiocarbimate salts with the best in vitro results were selected for in vivo experiments with Coffea arabica var Caturra and with the pollinator A. mellifera. The results were similar to those of Mancozeb, a broad-spectrum contact fungicide, with a good control of the disease and low toxicity to the honeybee. CONCLUSION: The zinc-dithiocarbimate complex salts have potential to control coffee leaf rust, with low toxicity to the pollinator insect. © 2022 Society of Chemical Industry.


Subject(s)
Basidiomycota , Coffea , Fungicides, Industrial , Animals , Bees , Carbon , Fungicides, Industrial/pharmacology , Nitrogen , Plant Diseases/prevention & control , Protons , Salts , Zinc/pharmacology
16.
Vaccines (Basel) ; 10(7)2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35891310

ABSTRACT

Currently, there is no licensed vaccine to protect against human visceral leishmaniasis (VL), a potentially fatal disease caused by infection with Leishmania parasites. In the current study, a recombinant chimeric protein ChimT was developed based on T-cell epitopes identified from the immunogenic Leishmania amastigote proteins LiHyp1, LiHyV, LiHyC and LiHyG. ChimT was associated with the adjuvants saponin (Sap) or monophosphoryl lipid A (MPLA) and used to immunize mice, and their immunogenicity and protective efficacy were evaluated. Both ChimT/Sap and ChimT/MPLA induced the development of a specific Th1-type immune response, with significantly high levels of IFN-γ, IL-2, IL-12, TNF-α and GM-CSF cytokines produced by CD4+ and CD8+ T cell subtypes (p < 0.05), with correspondingly low production of anti-leishmanial IL-4 and IL-10 cytokines. Significantly increased (p < 0.05) levels of nitrite, a proxy for nitric oxide, and IFN-γ expression (p < 0.05) were detected in stimulated spleen cell cultures from immunized and infected mice, as was significant production of parasite-specific IgG2a isotype antibodies. Significant reductions in the parasite load in the internal organs of the immunized and infected mice (p < 0.05) were quantified with a limiting dilution technique and quantitative PCR and correlated with the immunological findings. ChimT/MPLA showed marginally superior immunogenicity than ChimT/Sap, and although this was not statistically significant (p > 0.05), ChimT/MPLA was preferred since ChimT/Sap induced transient edema in the inoculation site. ChimT also induced high IFN-γ and low IL-10 levels from human PBMCs isolated from healthy individuals and from VL-treated patients. In conclusion, the experimental T-cell multi-epitope amastigote stage Leishmania vaccine administered with adjuvants appears to be a promising vaccine candidate to protect against VL.

17.
Int J Mol Sci ; 23(10)2022 May 14.
Article in English | MEDLINE | ID: mdl-35628297

ABSTRACT

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients' samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-ß, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs' roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.


Subject(s)
HTLV-I Infections , Leukemia-Lymphoma, Adult T-Cell , MicroRNAs , Computational Biology , HTLV-I Infections/genetics , Human T-lymphotropic virus 1 , Humans , Leukemia-Lymphoma, Adult T-Cell/genetics , Leukemia-Lymphoma, Adult T-Cell/virology , MicroRNAs/genetics
18.
Am J Otolaryngol ; 43(3): 103431, 2022.
Article in English | MEDLINE | ID: mdl-35460971

ABSTRACT

PURPOSE: Sialendoscopy is a minimally invasive procedure considered a paradigm shift in the treatment of obstructive sialadenitis. However, it shows an average need for revision procedure in up to 24% of operated cases. This study analyzed whether patient-related variables could predict the need for a revision during postoperative follow-up. METHODS: From 2012 to 2020, this prospective comparative study analyzed demographic data as well as preoperative responses to the "Manukau Salivary Symptoms Score" (MSSS) questionnaire as predictors of the need for a revision procedure due to symptoms recurrence. RESULTS: 188 sialendoscopies (39.4% for stones/60.6% for stenoses) in 112 parotid (59.6%) and 76 submandibular glands (40.4%) were included in this study. Forty patients (21.3%) required a revision procedure. The variable "Impact on quality of life" in the preoperative period of patients with sialoliths showed that the likelihood of a revision procedure increases by 33.6% with each increase in the 10-point Likert scale presented in the MSSS (p = 0.010, OR = 1336, CI = 1.071 to 1.667). This finding was not influenced by the location of the sialolith in the duct (p = 0.415), size (p = 0.058) or number of stones (P = 0.476). Other demographic variables related to the patient showed no association with the need of a revision procedure. CONCLUSION: Further studies should be performed to exclude the influence of other variables on the results; however, special attention should be given to patients who report a greater pre-operative impact on quality of life due to sialolithiasis. LEVEL OF EVIDENCE: II.


Subject(s)
Salivary Gland Calculi , Sialadenitis , Endoscopy/methods , Humans , Prospective Studies , Quality of Life , Retrospective Studies , Salivary Gland Calculi/surgery , Sialadenitis/surgery , Treatment Outcome
20.
Macromol Rapid Commun ; 43(9): e2100930, 2022 May.
Article in English | MEDLINE | ID: mdl-35267220

ABSTRACT

Cellulose nanocrystals (CNC)-based foams are promising tissue engineering materials that may facilitate implant-tissue integration and allow localized and controlled drug delivery. Herein, hybrid CNC-based foams, which are ultralightweight (30-100 mg cm-3 ), highly porous (>95%), ominiphilic and superabsorbent (1500-3000 wt% of water and/or toluene uptake) are obtained by the in situ condensation of poly(ethylene glycol) ditriethoxysilyl (TES-PEG-TES) into a 3D network, where silsesquioxane nanoparticles (SS-NP) are the crosslinking nodes, and CNC are entrapped forming ionic interactions, in a supramolecular structure. In a new approach, using 3-mercaptopropyltrimethoxysilane, sulfhydryl groups are inserted on the SS-NP periphery and S-nitrosated to enable the functionalization of SS-NP with S-nitrosothiol groups, which can nitric oxide (NO), in a process triggered by the hydration of the foams and modulated by their supramolecular structure. CNC-SS-PEG foams exhibit elevated thermal and structural stability, compressive strength compatible with various soft human tissues, and NO release rates (1-18 pmol mg-1 min-1 ) within the range of the beneficial NO actions. Thus, the CNC-SS-PEG foams herein described represent a new platform of supramolecular hybrid materials for localized delivery of NO, with potential uses in tissue engineering and other biomedical applications.


Subject(s)
Cellulose , Nanoparticles , Cellulose/chemistry , Humans , Nanoparticles/chemistry , Nitric Oxide , Tissue Engineering , Water/chemistry
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