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1.
Eur J Clin Invest ; : e14263, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849326

RESUMO

BACKGROUND: Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non-invasively measuring these parameters during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure-Strain Product (PSP), a novel speckle-tracking echocardiography parameter, (1) can correlate with pressure-volume catheter-based LVSWI and CPI, and (2) can be load-independent during the flow modification of V-A ECMO. METHODS: Nine Dorset-cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V-A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24-h observation, echocardiographic parameters as well as pressure-volume catheter-based LVSWI and CPI were simultaneously measured with X and following X-1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively. RESULTS: PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure-volume catheter-based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558). CONCLUSIONS: A novel echocardiographic parameter, PSP, may non-invasively predict pressure-volume catheter-based LVSWI and CPI in a load-independent manner in a cardiogenic shock supported by V-A ECMO.

2.
Stem Cell Res ; 79: 103470, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38896970

RESUMO

Autism spectrum disorder (ASD) is a complex developmental disorder characterized by challenges with social interactions and restricted/repetitive behaviors. Here, we recruited nine Qatari children of Arab ethnicity (males, aged 2-4 years), including six ASD subjects (n = 3 mild-to-moderate ASD and n = 3 severe ASD) and three control subjects. We generated induced pluripotent stem cell (iPSC) lines from PBMC samples of these subjects using non-integrating Sendai viral vectors. These iPSC lines were fully characterized and exhibited pluripotency characteristics, normal karyotypes, and trilineage differentiation potential. These iPSC lines provide valuable cell models for understanding ASD pathophysiology and developing new therapeutics for ASD.

3.
Can J Kidney Health Dis ; 11: 20543581241258812, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863503

RESUMO

Background: Cisplatin (Cis) is potent chemotherapy used to treating already many different types of cancer; however, it is found to correlate with nephrotoxicity and other adverse health consequences. Thymoquinone (TQ) is an antioxidant and anti-inflammatory molecule that may defend against the consequences of different chemotherapies. Thymoquinone uses, although, are negatively impacted by its weak solubility and inadequate biological availability. Objectives: This investigation examined the efficacy of a new nanoparticle (NP) absorbing TQ in an Ehrlich Ascites Carcinoma (EAC) mice model to address its low solubility, enhance its bioavailability, and protect against Cis-induced nephrotoxicity. Methods: Following 4 treatment groups were included in this research: (1) control, (2) EAC, (3) EAC + Cis + Thymoquinone nanoparticle (TQ-NP) treated, and (4) EAC + Cis-treated. Results: The study revealed that TQ-NP was efficacious in avoiding Cis-induced kidney problems in EAC mice, as well as restoring kidney function and pathology. Thymoquinone nanoparticle considerably reduced Cis-induced oxidative damage in renal tissue by augmenting antioxidant levels. According to tumor weight and histological investigation results, TQ-NP did not impair Cis's anticancer efficacy. Conclusion: Thymoquinone nanoparticle might be used as a potential drug along with Cis anticancer therapy to reduce nephrotoxicity and other side effects while maintaining Cis anticancer properties.


Contexte: Le cisplatine (CIS) est un puissant agent chimiothérapeutique utilisé pour le traitement de nombreux types de cancers. Le cisplatine est cependant corrélé à de la néphrotoxicité et à d'autres conséquences néfastes pour la santé. La thymoquinone (TQ) est une molécule antioxydante et anti-inflammatoire qui peut protéger contre les effets néfastes de différents agents chimiothérapeutiques. Les faibles solubilité et biodisponibilité de la TQ limitent toutefois son utilisation. Objectifs: Un modèle de souris atteintes d'un carcinome ascitique d'Ehrlich (souris EAC) a servi à vérifier l'efficacité d'une nouvelle nanoparticule (NP) absorbant la TQ pour remédier aux faibles solubilité et biodisponibilité de la TQ et protéger contre la néphrotoxicité induite par le CIS. Méthodologie: Les quatre groupes suivants ont été examinés: i) témoin; ii) souris EAC; iii) souris EAC traitées par CIS + TQ-NP (thymoquinone-nanoparticule); iv) souris EAC traitées par CIS. Résultats: L'étude a révélé que la TQ-NP était efficace pour éviter les problèmes rénaux induits par le CIS chez les souris EAC, de même que pour restaurer la fonction rénale et soigner la pathologie. En augmentant les niveaux d'antioxydants, la TQ-NP a considérablement réduit les dommages oxydatifs induits par le CIS dans le tissu rénal. Selon le poids des tumeurs et les résultats de l'étude histologique, la TQ-NP n'a pas altéré l'efficacité anticancéreuse du CIS. Conclusion: La TQ-NP pourrait potentiellement être utilisée avec le traitement anticancéreux par CIS afin de réduire la néphrotoxicité et les autres effets secondaires, sans altérer les propriétés anticancer du CIS.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38932684

RESUMO

Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle hypertrophy in response to RT when compared to younger adults. This may be attributed to underlying molecular processes that are dysregulated by aging and exacerbated by improperly prescribed RT weekly volume, intensity, and/or frequency doses. MicroRNA (miRNA) are key epigenetic regulators that impact signaling pathways and protein expression within cells, are dynamic and responsive to exercise stimuli, and are often dysregulated in diseases. In this study, we used untargeted miRNA-seq to examine miRNA in skeletal muscle and serum-derived exosomes of older adults (n = 18, 11M/7F, 66±1y) who underwent 3x/wk RT for 30 weeks [e.g., high intensity 3x/wk (HHH, n = 9) or alternating high-low-high intensity (HLH, n = 9)], after a standardized four-week wash-in. Within each tissue, miRNAs were clustered into modules based on pairwise correlation using Weighted Gene Correlation Network Analysis (WGCNA). Modules were tested for association with the magnitude of RT-induced thigh lean mass (TLM) change (as measured by DXA). While no modules were unique to training dose, we identified miRNA modules in skeletal muscle associated with TLM gains irrespective of exercise dose. Using miRNA-target interactions, we analyzed key miRNAs in significant modules for their potential regulatory involvement in biological pathways. Findings point toward potential miRNAs that may be informative biomarkers and could also be evaluated as potential therapeutic targets as an adjuvant to RT in order to maximize skeletal muscle mass accrual in older adults.

7.
J Pharm Biomed Anal ; 243: 116109, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38518458

RESUMO

An innovative ecofriendly high-performance thin layer chromatographic (HPTLC) method with spectrophotometric detection for simultaneous determination of Tramadol (TMD), Tapentadol (TAP), and Venlafaxine (VEN) in seized dosage forms was presented. Our method was conducted to achieve separation following the optimal conditions: pre-coated silica gel plates using a green mobile phase (heptane: acetone: ammonia, 7:3:0.5 v/v), with absorbance scanning at 272 nm. The validation of the method was done following International Conference on Harmonization (ICH) guidelines, demonstrates linearity, accuracy, precision, selectivity, robustness, and system suitability. Separation was achieved with a detection limit of 0.34, 0.16, and 0.084 (ug/band) for TMD, TAP, and VEN, respectively, the method successfully analyzes seized samples. Trueness is confirmed through a high degree of similarity between HPTLC and gas chromatography results. The study's ecofriendly approach, simplicity, and selectivity position it as a promising method for efficient, on-site monitoring of seized samples.


Assuntos
Tramadol , Tapentadol , Cloridrato de Venlafaxina , Cromatografia em Camada Fina/métodos , Preparações Farmacêuticas , Reprodutibilidade dos Testes
8.
Toxicol Res (Camb) ; 13(2): tfae028, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38455639

RESUMO

Background: Aluminum, a well-recognized neurotoxin, is implicated in various neurodegenerative disorders. Moringa oleifera (M. oleifera), known as a miracle tree, is utilized as a functional food and nutritional supplement. This study investigates the potential preventive effects of M. oleifera extract on aluminum chloride (AlCl3)-induced cortical neurodegeneration in rats. Materials and methods: Therefore, 24 adult male Wistar rats were randomly divided into four distinct groups: negative control, M. oleifera extract (MOE), AlCl3, and AlCl3 + MOE. Treatments were administered orally for 28 consecutive days. Cognitive performance, brain oxidative/nitrosative stress, neuroinflammation, apoptotic-cell death, and associated histopathological alterations were assessed. Results: Our results showed that MOE improved spatial learning and memory, enhanced antioxidant superoxide dismutase enzyme activity, antagonized nitrosative stress, reduced inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), decreased caspase-3, increased Bcl-2, and facilitated repair of cortical and hippocampal structures. Conclusions: We concluded that MOE exhibits protective effects against cortical neurodegeneration, making it a promising supplement to counteract aluminum-induced neurotoxic effects.

9.
Molecules ; 29(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38542873

RESUMO

Type 2 diabetes mellitus is a multifactorial disorder whose primary manifestation usually initiates with elevated blood sugar levels. Several antidiabetic agents are used to manage type 2 diabetes mellitus, of which empagliflozin is an oral sodium-glucose co-transporter (SGLT-2) inhibitor in the kidney. This research aims to develop and validate a simple analytical method for determining empagliflozin levels in biological fluid and to further evaluate grapefruit juice's impact on empagliflozin pharmacokinetics in rats. High-Performance Liquid Chromatography (HPLC) was used to establish a simple, rapid, and accurate method for determining empagliflozin levels in rat plasma, in the presence of grapefruit juice. Four groups of rats (n = 10 rats in each) were used in the preclinical study. Group A (healthy rats) received empagliflozin alone; Group B (healthy rats) received empagliflozin with grapefruit; Group C (diabetic rats) received empagliflozin with grapefruit; and Group D (healthy, negative control) received no medication. The rats (n = 10) were given grapefruit juice instead of water for seven days before receiving the empagliflozin dose (0.16 mg/kg). Some pharmacokinetic parameters for each group were determined. The maximum plasma concentration (Cmax) and area under the curve (AUC) of empagliflozin in Group A without grapefruit intake were 730 ng/mL and 9264.6 ng × h/mL, respectively, with Tmax (2 h). In Group B, Cmax was 1907 ng/mL and AUC was 10,290.75 ng × h/mL in the presence of grapefruit, with Tmax (1 h); whereas, in Group C, the Cmax was 2936 ng/mL and AUC was 18657 ng × h/mL, with Tmax (2 h). In conclusion, our results showed that the co-administration of grapefruit with empagliflozin should be cautiously monitored and avoided, in which grapefruit elevates the plasma level of empagliflozin. This may be attributed to the inhibition of the uridine enzyme in the grapefruit by hesperidin, naringin, and flavonoid.


Assuntos
Compostos Benzidrílicos , Citrus paradisi , Citrus , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Glucosídeos , Ratos , Animais , Cromatografia Líquida de Alta Pressão , Citrus/química , Bebidas , Área Sob a Curva
11.
Front Psychiatry ; 15: 1333534, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414501

RESUMO

Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impaired social interaction and communication and the occurrence of stereotyped and repetitive behaviors. Several studies have reported altered cytokine profiles in ASD and hence may serve as potential diagnostic biomarkers of the disorder. This study aims to identify diagnostic biomarkers for ASD in a well-defined study cohort in Qatar. Methods: We measured the protein levels of 45 cytokines in the plasma samples of age- and gender-matched children (2-4 years) with ASD (n = 100) and controls (n = 60) using a Luminex multiplex assay. We compared the differences in the levels of these cytokines between the two study groups and then fitted the significantly altered cytokines into a logistic regression model to examine their diagnostic potential for ASD. Results: We found elevated levels of IFN-γ, FGF-2, IL-1RA, and IL-13 and reduced levels of eotaxin, HGF, IL-1 alpha, IL-22, IL-9, MCP-1, SCF, SDF-1 alpha, VEGFA, and IP-10 in the plasma of children with ASD compared to controls. Furthermore, we observed that elevated levels of IFN-γ (odds ratio (OR) = 1.823; 95% (confidence interval) CI = 1.206, 2.755; p = 0.004) and FGF-2 (OR = 2.528; 95% CI = 1.457, 4.385; p < 0.001) were significantly associated with increased odds of ASD, whereas reduced levels of eotaxin (OR = 0.350; 95% CI = 0.160, 0.765; p = 0.008) and HGF (OR = 0.220; 95% CI = 0.070, 0.696; p = 0.010) were significantly associated with lower odds of ASD relative to controls. The combination of these four cytokines revealed an area under the curve (ROC-AUC) of 0.829 (95% CI = 0.767, 0.891; p < 0.001), which demonstrates the diagnostic accuracy of the four-cytokine signature. Conclusions: Our results identified a panel of cytokines that could discriminate between children with ASD and controls in Qatar. In addition, our findings support the predominance of a Th1 immune phenotype in ASD children and emphasize the need to validate these results in larger populations.

12.
Clin Rheumatol ; 43(3): 1015-1021, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38294724

RESUMO

BACKGROUND: Lupus nephritis (LN) is one of the major complications associated with Systemic Lupus Erythematosus (SLE). Activated leukocyte cell adhesion molecule (ALCAM or CD166) is a promising urine biomarker that binds to CD6, a receptor found on lymphocytes. This binding results in T-cell activation, proliferation, and recruitment, which causes tissue inflammation and may explain the pathophysiology of LN. AIM OF WORK: Investigate the urinary ALCAM level in SLE, study its relationship to disease activity, and clarify the association with LN activity and histopathology. PATIENTS AND METHODS: A case-control study was performed on 60 patients with SLE and 20 matched controls. The SLE disease activity index (SLEDAI) and the activity of renal disease (rSLEDAI) were evaluated. Renal biopsy and uALCAM levels were also investigated. RESULTS: Urinary ALCAM levels were higher significantly in active LN patients than inactive LN patients, active and inactive non-LN SLE, and the control group (p < 0.001). The cut-off value for identifying active and inactive LN was above 270 ng/mg (p < 0.001). ALCAM levels were greater in proliferative (class III, IV, and IV/V) than in non-proliferative (class II and V) LN (p < 0.001). ALCAM exhibited high positive correlations with SLEDAI and rSLEDAI (p < 0.001 each) and negative significant correlations with C3 (p < 0.001) and C4 (p = 0.005). CONCLUSION: Urinary ALCAM is a sensitive biomarker evaluating LN in SLE patients. Levels above 270 ng/mg can help distinguish between active and inactive LN. ALCAM levels are correlated positively with SLEDAI and rSLEDAI but have a negative correlation with C3 and C4. Key Points • Urinary ALCAM shows promise as a biomarker for evaluating kidney dysfunction in SLE patients. • It is a non-invasive marker that can differentiate between proliferative and non-proliferative LN. • A urinary ALCAM level above 270 ng/mg can indicate active LN, while lower levels indicate inactive LN. • Urinary ALCAM levels are correlated positively with SLEDAI and rSLEDAI scores but correlated negatively with C3 and C4.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/patologia , Molécula de Adesão de Leucócito Ativado , Estudos de Casos e Controles , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/urina , Biomarcadores , Antígenos CD
13.
Luminescence ; 39(1): e4609, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37880857

RESUMO

The new drug linagliptin belongs to the class of dipeptidyl peptidase-4 enzyme inhibitors. Linagliptin is used to treat type 2 diabetes and is taken orally either alone or in combination with other drugs. In this instance, a new, simple, and economical technique for analyzing linagliptin was developed by the effective use of a pyrrolidone derivative. The primary amine group of linagliptin permits its condensation with ninhydrin (0.14% w/v) to produce a fluorescent product in the presence of phenylacetaldehyde (0.02% v/v). All experimental parameters were carefully examined and adjusted in order to monitor the generation of the pyrrolidone derivative at excitation and emission wavelengths of 385 and 475 nm, respectively. The calibration graph was made by plotting the intensity of the fluorescence in relation to linagliptin concentration. A significant linearity was found for values ranging from 20 to 460 ng/mL. The process's validity has been verified by a thorough assessment of the instructions provided by the International Conference on Harmonization (ICH). The results indicate excellent uniformity with a reference method, showing that there is no substantial difference in precision and accuracy. The proposed approach was utilized for determining linagliptin in real rat plasma successfully owing to its high sensitivity. Additionally, the proposed approach was evaluated using the Eco-Scale evaluation tool and showed a high degree of eco-friendliness (86/100).


Assuntos
Acetaldeído/análogos & derivados , Diabetes Mellitus Tipo 2 , Linagliptina , Animais , Ratos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ninidrina/química , Pirrolidinonas
14.
Saudi J Biol Sci ; 30(11): 103792, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37711970

RESUMO

A gradual loss of neuronal function or structure causes neurodegenerative disorders such as Parkinson's and Alzheimer's. Neurological damage might cause cell death. Acrolein is a high-risk air and water contaminant that causes neurodegenerative disorders. Quercetin has several strategies for treating neurodegenerative disorders but has limited bioavailability inside the body. One of the hypotheses offered to improve quercetin's bioavailability is to convert it into quercetin nanoparticles. This study aims to comprehend the immunohistochemical devastation that might arise in the cerebellum because of acrolein treatment. Furthermore, the protective and ameliorative roles of quercetin nanoparticles against oxidative stress and neurotoxicity induced in mice by acrolein were assessed. Ninety male albino rats weighing 120 to 200 g were used in the present investigation. The animals were split up into the following six groups: the control group, the acrolein-treated group: animals were given acrolein (3 mg/kg) for 30 days, quercetin nanoparticles treated group: animals were given quercetin nanoparticles (30 mg/kg) for 30 days. The administration of acrolein was found to be connected to immunohistochemical abnormalities in the cerebellum. Marked differences were observed in Bax, Bcl-2, TNF-α, and GFAP expressions in the cerebellum. Treatment of rats with quercetin nanoparticles either before or after treatment with acrolein has been found to preserve the cerebellum tissues from the toxic impacts and oxidative stress induced by acrolein. This may open the door to more nanomedicine studies and a new avenue for employing nanoparticles as a therapeutic intervention in neurodegenerative illnesses.

15.
Urol Case Rep ; 51: 102552, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37701419

RESUMO

This case report presents a young male patient with a 3-month history of a rapidly growing lower abdominal mass associated with lower urinary tract symptoms and recurrent urinary tract infection. Pelvic magnetic resonance imaging showed a large congenital cyst in the right seminal vesicle having a mass effect on the urinary bladder, rectum, and left ureter. Histopathologic findings from exploratory laparotomy showed an epidermal inclusion cyst with secondary inflammation and suppuration. This report adds to the literature by describing this unique location of an epidermoid cyst within the seminal vesicle.

16.
Pak J Pharm Sci ; 36(4): 1031-1043, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37599476

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is globally concerning for overall health. The viral burden is diagnosed by the positive cycle threshold value (Ct-value) of the real-time reverse transcription polymerase chain reaction (RT-PCR) assay. So far, no effective therapy has been established for this viral infection. This research aims to investigate the impact of zinc therapy on viral burden, salivary zinc levels and serum specific antibody levels versus SARS-CoV-2 spike antigen in subjects with infection. The correlation between viral burden and salivary zinc levels was also studied. 75 participants were included, classified as 25 non SARS-CoV-2 healthy individuals, 25 SARS-CoV-2 patients and 25 SARS-CoV-2 patients receiving zinc sulphate daily for 30 days. Results revealed markedly low salivary zinc levels in SARS-CoV-2 cases, which were closely linked with a high viral burden versus healthy participants. Marked elevations in serum IgM, IgG, and IgG1 antibody levels in infected patients versus healthy participants were also noticed. Treatment with zinc markedly boosted the salivary zinc levels and lowered the viral burden in SARS-CoV-2 cases. Serum IgM, IgG and IgG1 antibody levels were downregulated in SARS-CoV-2 treated with zinc. Conclusion: Zinc therapy may be an efficient therapeutic approach for SARS-CoV-2 viral eradication.


Assuntos
COVID-19 , Zinco , Humanos , Zinco/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Relevância Clínica , SARS-CoV-2 , Imunoglobulina G , Imunoglobulina M , Teste para COVID-19
17.
Micron ; 173: 103517, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37556900

RESUMO

Transmission electron microscopy (TEM) is a powerful technique that enables visualization of structural details inside cells. Prior to TEM imaging, biological samples must undergo several preparation steps that are optimized according to the sample type. Currently, there are limited protocols for the preparation of blood samples for TEM imaging. Here, we provide a detailed step-by-step method for preparing blood samples for TEM imaging. This protocol enables robust visualization of the ultrastructures of blood immune cells. In addition, we describe the typical cellular features that can be used to distinguish between different immune cells in the blood, such as neutrophils, eosinophils, monocytes, and lymphocytes. This protocol is useful for studying ultrastructural changes in blood immune cells under various physiological and disease conditions.


Assuntos
Neutrófilos , Microscopia Eletrônica de Transmissão
18.
BMC Psychiatry ; 23(1): 471, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37381024

RESUMO

This study aimed to provide a national estimate of the prevalence of the high risk of autism spectrum disorder (ASD) and their determinants. A national screening survey was conducted for 41,640 Egyptian children aged 1 to 12 years in two phases. Tools used were Vineland's Adaptive Behavior Scales, Modified Checklist for Autism in Toddlers, Gilliam Autism Rating scale, and Denver II Developmental screening test. The overall prevalence of children at high risk of ASD was 3.3% (95% CI:3.1%-3.5%). Children living without mothers in homes, suffered from convulsions (AOR = 3.67; 95%CI:2.8-4.8), a history of cyanosis after birth (AOR = 1.87; 95% CI:1.35-2.59) or history of LBW babies (AOR = 1.53; 95% CI:1.23-1.89) carried higher odds of being at high risk of ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Lactente , Feminino , Humanos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Egito/epidemiologia , Adaptação Psicológica , Lista de Checagem
19.
World J Hepatol ; 15(5): 585-608, 2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37305370

RESUMO

Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV "cure" is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.

20.
Molecules ; 28(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37175361

RESUMO

In this study, poly(AA-co-ACMO) and polyurethane-based nanofibers were prepared in a ratio of 1:1 (NF11) and 2:1 (NF21) as antimicrobial carriers for chronic wound management. Different techniques were used to characterize the nanofibers, and poly(AA-co-ACMO) was mostly found on the surface of PU. With an increase in poly(AA-co-ACMO) dose from 0 (PU) and 1:1 (NF11) to 2:1 (NF21) in the casting solution, the contact angle (CA) was reduced from 137 and 95 to 24, respectively, and hydrophilicity was significantly increased. As most medications inhibit biological processes by binding to a specific protein, in vitro protein binding was investigated mechanistically using a stopped-flow technique. Both NF11 and NF21 bind to BSA via two reversible steps: a fast second-order binding followed by a slow first-order one. The overall parameters for NF11 (Ka = 1.1 × 104 M-1, Kd = 89.0 × 10-6, ΔG0 = -23.1 kJ mol-1) and NF21 (Ka = 189.0 × 104 M-1, Kd = 5.3 × 10-6 M, ΔG0 = -27.5 kJ mol-1) were determined and showed that the affinity for BSA is approximately (NF11)/(NF21) = 1/180. This indicates that NF21 has much higher BSA affinity than NF11, although BSA interacts with NF11 much faster. NF21 with higher hydrophilicity showed effective antibacterial properties compared to NF11, in agreement with kinetic data. The study provided an approach to manage chronic wounds and treating protein-containing wastewater.


Assuntos
Nanofibras , Poliuretanos , Poliuretanos/química , Nanofibras/química , Polímeros/química , Antibacterianos/farmacologia , Interações Hidrofóbicas e Hidrofílicas
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