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1.
World J Orthop ; 15(6): 570-577, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38947270

RESUMO

BACKGROUND: The preferred treatment for distal humeral intercondylar fractures is open reduction and internal fixation. While there is consensus about the posterior approach, several posterior approaches have been developed. It is debatable as to which approach is best. AIM: To compare triceps reflecting anconeus pedicle (TRAP) and olecranon osteotomy approaches for internal fixation of distal humeral intercondylar fracture. METHODS: In total, 40 cases of Arbeitsgemeinschaft für Osteosynthesefragen/Association of the Study of Internal Fixation type C, closed, and Gustilo type I intercondylar humeral fractures were included. Patients ranged in age from 18 years to 70 years. The patients were randomized into two groups: TRAP group and olecranon osteotomy group, with 20 cases in each. All were followed up at 6 wk, 3 months, 6 months, and 12 months. Functional outcomes were measured in terms of flexion-extension arc, Disabilities of Arm, Shoulder and Hand score, and Mayo Elbow Performance Score. RESULTS: The mean age was 43.2 years in the TRAP group and 37.5 years in the olecranon osteotomy group. The mean operative time and mean duration of hospital stay in the TRAP group were significantly higher than in the olecranon osteotomy group (119.5 vs 111.5 min and 9.85 vs 5.45 d, respectively). The mean arc of flexion-extension, Disabilities of Arm, Shoulder and Hand score, and Mayo Elbow Performance Score were comparable without any significant difference in the groups at the 12-month follow-up (107.0 vs 106.2, 18.3 vs 15.7, and 84.2 vs 86.2, respectively). Ulnar paresthesia and superficial infections were comparable in both groups (2 cases vs 3 cases and 3 cases vs 2 cases, respectively). Hardware prominence was significantly higher in the olecranon osteotomy group, mostly due to tension band wiring. CONCLUSION: Both approaches were equivalent, but there is a need for further study including higher numbers of subjects and longer study duration to prove the benefits of one approach over the other.

2.
Nat Struct Mol Biol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951623

RESUMO

The development of precise RNA-editing tools is essential for the advancement of RNA therapeutics. CRISPR (clustered regularly interspaced short palindromic repeats) PspCas13b is a programmable RNA nuclease predicted to offer superior specificity because of its 30-nucleotide spacer sequence. However, its design principles and its on-target, off-target and collateral activities remain poorly characterized. Here, we present single-base tiled screening and computational analyses that identify key design principles for potent and highly selective RNA recognition and cleavage in human cells. We show that the de novo design of spacers containing guanosine bases at precise positions can greatly enhance the catalytic activity of inefficient CRISPR RNAs (crRNAs). These validated design principles (integrated into an online tool, https://cas13target.azurewebsites.net/ ) can predict highly effective crRNAs with ~90% accuracy. Furthermore, the comprehensive spacer-target mutagenesis revealed that PspCas13b can tolerate only up to four mismatches and requires ~26-nucleotide base pairing with the target to activate its nuclease domains, highlighting its superior specificity compared to other RNA or DNA interference tools. On the basis of this targeting resolution, we predict an extremely low probability of PspCas13b having off-target effects on other cellular transcripts. Proteomic analysis validated this prediction and showed that, unlike other Cas13 orthologs, PspCas13b exhibits potent on-target activity and lacks collateral effects.

3.
Chem Biol Interact ; 397: 111087, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823536

RESUMO

Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects. Our study focuses on Asphodelus microcarpus, a plant renowned for traditional anti-inflammatory uses. Recent investigations into its phenolic-rich flowers, notably abundant in luteolin derivatives, reveal its potential as a natural source of XO inhibitors. In the present research, XO inhibition by an ethanolic flowers extract from A. microcarpus is reported. In silico docking studies have highlighted luteolin derivatives as potential XO inhibitors, and molecular dynamics support that luteolin 7-O-glucoside has the highest binding stability compared to other compounds and controls. In vitro studies confirm that luteolin 7-O-glucoside inhibits XO more effectively than the standard inhibitor allopurinol, with an IC50 value of 4.8 µg/mL compared to 11.5 µg/mL, respectively. These findings underscore the potential therapeutic significance of A. microcarpus in managing conditions related to XO activity. The research contributes valuable insights into the health-promoting properties of A. microcarpus and its potential application in natural medicine, presenting a promising avenue for further exploration in disease management.


Assuntos
Inibidores Enzimáticos , Luteolina , Simulação de Acoplamento Molecular , Xantina Oxidase , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Luteolina/química , Luteolina/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Simulação de Dinâmica Molecular , Flores/química , Alopurinol/farmacologia , Alopurinol/química , Humanos , Sítios de Ligação
4.
Nanotechnology ; 35(36)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38838648

RESUMO

Ascorbic acid (AA), known as vitamin C, is a vital bioactive compound that plays a crucial role in several metabolic processes, including the synthesis of collagen and neurotransmitters, the removal of harmful free radicals, and the uptake of iron by cells in the human intestines. As a result, there is an absolute need for a highly selective, sensitive, and economically viable sensing platform for AA detection. Herein, we demonstrate a Pt-decorated MoS2for efficient detection of an AA biosensor. MoS2hollow rectangular structures were synthesized using an easy and inexpensive chemical vapor deposition approach to meet the increasing need for a reliable detection platform. The synthesized MoS2hollow rectangular structures are characterized through field effect scanning electron microscopy (FESEM), energy-dispersive spectroscopy elemental mapping, Raman spectroscopy, and x-ray photoelectron spectroscopy. We fabricate a chemiresistive biosensor based on Pt-decorated MoS2that measures AA with great precision and high sensitivity. The experiments were designed to evaluate the response of the Pt-decorated MoS2biosensor in the presence and absence of AA, and selectivity was evaluated for a variety of biomolecules, and it was observed to be very selective towards AA. The Pt-MoS2device had a higher response of 125% against 1 mM concentration of AA biomolecules, when compared to that of all other devices and 2.2 times higher than that of the pristine MoS2device. The outcomes of this study demonstrate the efficacy of Pt-decorated MoS2as a promising material for AA detection. This research contributes to the ongoing efforts to enhance our capabilities in monitoring and detecting AA, fostering advancements in environmental, biomedical, and industrial applications.


Assuntos
Ácido Ascórbico , Técnicas Biossensoriais , Dissulfetos , Molibdênio , Platina , Ácido Ascórbico/análise , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Dissulfetos/química , Molibdênio/química , Platina/química , Humanos , Análise Espectral Raman/métodos
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124627, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38880073

RESUMO

The SERS spectra of six bacterial biomarkers, 2,3-DHBA, 2,5-DHBA, Pyocyanin, lipoteichoic acid (LTA), Enterobactin, and ß-carotene, of various concentrations, were obtained from silver nanorod array substrates, and the spectral peaks and the corresponding vibrational modes were identified to classify different spectra. The spectral variations in three different concentration regions due to various reasons have imposed a challenge to use classic calibration curve methods to quantify the concentration of biomarkers. Depending on baseline removal strategy, i.e., local or global baseline removal, the calibration curve differed significantly. With the aid of convolutional neural network (CNN), a two-step process was established to classify and quantify biomarker solutions based on SERS spectra: using a specific CNN model, a remarkable differentiation and classification accuracy of 99.99 % for all six biomarkers regardless of the concentration can be achieved. After classification, six regression CNN models were established to predict the concentration of biomarkers, with coefficient of determination R2 > 0.97 and mean absolute error (MAE) < 0.27. The feature of important calculations indicates the high classification and quantification accuracies were due to the intrinsic spectral features in SERS spectra. This study showcases the synergistic potential of SERS and advanced machine learning algorithms and holds significant promise for bacterial infection diagnostics.

6.
Mol Neurobiol ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898197

RESUMO

Proliferation of specific nucleotide sequences within the coding and non-coding regions of numerous genes has been implicated in approximately 40 neurodegenerative disorders. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), a neurodegenerative disorder, is distinguished by a pathological triad of sensory neuropathy, bilateral vestibular areflexia and cerebellar impairments. It manifests in adults gradually and is autosomal recessive and multi-system ataxia. Predominantly, CANVAS is associated with biallelic AAGGG repeat expansions in intron 2 of the RFC1 gene. Although various motifs have been identified, only a subset induces pathological consequences, by forming stable secondary structures that disrupt gene functions both in vitro and in vivo. The pathogenesis of CANVAS remains a subject of intensive research, yet its precise mechanisms remain elusive. Herein, we aim to comprehensively review the epidemiology, clinical ramifications, molecular mechanisms, genetics, and potential therapeutics in light of the current findings, extending an overview of the most significant research on CANVAS.

7.
Ann Indian Acad Neurol ; 27(3): 236-243, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38902872

RESUMO

BACKGROUND: Several observational studies have reported the prevalence of cerebral microbleeds (CMBs) and their risk factors in an elderly population. Any information in this regard is currently lacking from India. Aim of this study was to estimate the prevalence, risk factors of CMBs, and association with cognition in an Indian urban population aged 50 years and above. METHODS: Household surveys were conducted as part of ongoing Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) study in areas of urban Delhi. Magnetic resonance imaging of the brain was performed in 2599 participants. Using standard neuropsychological battery, mean Z-scores for each domain (memory, executive, information) were derived. Binary and stepwise logistic regression models were used to determine associated risk factors for the presence of CMB and its association with cognitive domains. RESULTS: The prevalence of CMBs was 14.42% (95% confidence interval [CI]: 13.06-15.73). Of these, 203 (7.81%) participants had single CMBs and 172 (6.61%) had multiple microbleeds (≥2). Higher prevalence was observed in older age (60-70 years: odds ratio [OR]: 1.25 [95% CI: 0.93-1.67]; 70-80 years: OR: 2.05 [95% CI: 1.48-2.84]; ≥80 years: OR: 3.27 [95% CI: 1.97-5.44]) compared to individuals in the age group 50-60 years. History of stroke (OR: 2.97 [95% CI: 1.56-5.66]), hypertension (OR: 1.36 [95% CI: 1.05-1.75]), and smoking (OR: 1.43 [95% CI: 1.11-1.85]) was associated with at least one CMB. Multiple CMBs were associated with worse scores in memory and executive domains. CONCLUSION: Older age, hypertension, history of stroke, and history of smoking emerged as important risk factors for the presence of multiple CMBs. Follow-up study is required to determine implications of CMBs.

9.
Transfus Clin Biol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909678

RESUMO

BACKGROUND AND OBJECTIVES: Hemolytic transfusion reactions (HTRs) pose significant risks in transfused patients, with anti-A and anti-B antibodies in donor plasma being potential contributing factors. Despite advancements in component preparation, HTRs remain a concern, particularly with apheresis-derived platelets. This study aimed to determine the prevalence of high anti-A and anti-B titers among A, B, and O blood group donors and to explore factors associated with high titers. MATERIALS AND METHODS: A cross-sectional observational study was conducted over 18 months, enrolling 978 participants from a tertiary care teaching hospital in Western India. Anti-A and anti-B titers were determined using the Conventional Tube Technique (CTT). Statistical analysis assessed correlations between high titers and demographic factors. RESULTS: The majority of participants were young males (98.8%). Prevalence of high titers for IgM anti-A was 12.2% and IgG anti-A was 2.5%. For anti-B, IgM titers were 2.3% and IgG titers were 0.2%. The prevalence of dangerous O was found to be 14.1%, while 3.52% and 10.5% of A and B blood group donors were found to have high titers, respectively. Factors associated with high titers included female gender, vegetarian diet, age <30 years, and O blood group. CONCLUSION: The study sheds additional light and provides supplementary information regarding the prevalence and correlation of high anti-A and anti-B titers among O, A and B blood donors. Understanding these factors is crucial for optimizing transfusion safety protocols, including selective screening of platelet units and tailored transfusion strategies based on donor characteristics.

10.
Int J Artif Organs ; : 3913988241259969, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904355

RESUMO

Artificial disc replacement (ADR) is a clinical procedure used to diagnose cervical degenerative disc disease, preserving range of motion (ROM) at the fixation level and preventing adjacent segment degeneration (ASD). This study analyzed the biomechanics of ADR by examining range of motion (ROM), stress levels in bone and implants, and strain in the bone-implant interface using multi-scale loadings. The study focused on single- and double-level patients across various loading scales during physiological motions within the cervical spine. Results showed increased ROM in single-level and double-level fixations during physiological loadings, while ROM decreased at the adjacent level of fixation with the intact cervical spine model. The Prodisc-Implant metal endplate experienced a maximum von Mises stress of 432 MPa during axial rotation, confirming the long durability and biomechanical performance of the bone-implant interface.

11.
PLoS One ; 19(6): e0296616, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38829877

RESUMO

Early prognostication of patient outcomes in intracerebral hemorrhage (ICH) is critical for patient care. We aim to investigate protein biomarkers' role in prognosticating outcomes in ICH patients. We assessed 22 protein biomarkers using targeted proteomics in serum samples obtained from the ICH patient dataset (N = 150). We defined poor outcomes as modified Rankin scale score of 3-6. We incorporated clinical variables and protein biomarkers in regression models and random forest-based machine learning algorithms to predict poor outcomes and mortality. We report Odds Ratio (OR) or Hazard Ratio (HR) with 95% Confidence Interval (CI). We used five-fold cross-validation and bootstrapping for internal validation of prediction models. We included 149 patients for 90-day and 144 patients with ICH for 180-day outcome analyses. In multivariable logistic regression, UCH-L1 (adjusted OR 9.23; 95%CI 2.41-35.33), alpha-2-macroglobulin (aOR 5.57; 95%CI 1.26-24.59), and Serpin-A11 (aOR 9.33; 95%CI 1.09-79.94) were independent predictors of 90-day poor outcome; MMP-2 (aOR 6.32; 95%CI 1.82-21.90) was independent predictor of 180-day poor outcome. In multivariable Cox regression models, IGFBP-3 (aHR 2.08; 95%CI 1.24-3.48) predicted 90-day and MMP-9 (aOR 1.98; 95%CI 1.19-3.32) predicted 180-day mortality. Machine learning identified additional predictors, including haptoglobin for poor outcomes and UCH-L1, APO-C1, and MMP-2 for mortality prediction. Overall, random forest models outperformed regression models for predicting 180-day poor outcomes (AUC 0.89), and 90-day (AUC 0.81) and 180-day mortality (AUC 0.81). Serum biomarkers independently predicted short-term poor outcomes and mortality after ICH. Further research utilizing a multi-omics platform and temporal profiling is needed to explore additional biomarkers and refine predictive models for ICH prognosis.


Assuntos
Biomarcadores , Hemorragia Cerebral , Aprendizado de Máquina , Proteômica , Humanos , Hemorragia Cerebral/sangue , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Masculino , Feminino , Biomarcadores/sangue , Prognóstico , Proteômica/métodos , Idoso , Pessoa de Meia-Idade , Algoritmos
12.
Microb Pathog ; 193: 106763, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925344

RESUMO

Increasing incidences of fungal infections and prevailing antifungal resistance in healthcare settings has given rise to an antifungal crisis on a global scale. The members of the genus Candida, owing to their ability to acquire sessile growth, are primarily associated with superficial to invasive fungal infections, including the implant-associated infections. The present study introduces a novel approach to combat the sessile/biofilm growth of Candida by fabricating nanofibers using a nanoencapsulation approach. This technique involves the synthesis of tyrosol (TYS) functionalized chitosan gold nanocomposite, which is then encapsulated into PVA/AG polymeric matrix using electrospinning. The FESEM, FTIR analysis of prepared TYS-AuNP@PVA/AG NF suggested the successful encapsulation of TYS into the nanofibers. Further, the sustained and long-term stability of TYS in the medium was confirmed by drug release and storage stability studies. The prepared nanomats can absorb the fluid, as evidenced by the swelling index of the nanofibers. The growth and biofilm inhibition, as well as the disintegration studies against Candida, showed 60-70 % biofilm disintegration when 10 mg of TYS-AuNP@PVA/AG NF was used, hence confirming its biological effectiveness. Subsequently, the nanofibers considerably reduced the hydrophobicity index and ergosterol content of the treated cells. Considering the challenges associated with the inhibition/disruption of fungal biofilm, the fabricated nanofibers prove their effectiveness against Candida biofilm. Therefore, nanocomposite-loaded nanofibers have emerged as potential materials that can control fungal colonization and could also promote healing.

13.
Pediatrics ; 154(1)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38872621

RESUMO

BACKGROUND AND OBJECTIVE: There is a paucity of pooled synthesized data on the epidemiology of neonatal acute kidney injury (AKI). Our objective with this study is to systematically assess the worldwide incidence of AKI in neonates. METHODS: We searched 3 electronic databases (Embase, PubMed, Web of Sciences) from January 2004 to December 2022 without language restrictions. We included cohort and cross-sectional studies that reported the incidence of AKI or associated mortality in neonates. Eligible studies had at least 10 participants and used standard criteria (Acute Kidney Injury Network/Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (pRIFLE)/ Kidney Disease Improving Global Outcomes) to define AKI. Two authors independently retrieved data on demographic characteristics, clinical setting, and outcomes (incidence and AKI-associated mortality) using a semi-structured proforma and assessed the risk of bias. We used a random-effects meta-analysis to calculate pooled estimates with 95% confidence intervals. RESULTS: We included 201 studies (98 228 participants) from 45 countries. The incidence of any stage AKI was 30% (95% confidence interval 28-32), and that of severe AKI was 15% (14-16). Overall, AKI-associated mortality was 30% (27-33). The odds of mortality were higher (odds ratio 3.4; 2.9-4.0) in neonates with AKI compared with those without AKI. We found that perinatal asphyxia, sepsis, patent ductus arteriosus, necrotizing enterocolitis, and nephrotoxic medications were significant risk factors for AKI. Significant heterogeneity in the pooled estimates was a limitation of this study. CONCLUSIONS: AKI was observed in one-third of the neonates and was associated with increased risk of mortality. The incidence of AKI was almost similar in neonates with perinatal asphyxia and sepsis, but mortality was higher in the former group.


Assuntos
Injúria Renal Aguda , Humanos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/mortalidade , Recém-Nascido , Incidência , Fatores de Risco
14.
Acupunct Med ; : 9645284241256670, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845551
15.
Bioinformation ; 20(4): 391-393, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854768

RESUMO

A comparative analysis and assessment of the compressive strength (CS) and diametral tensile strength (DTS) between conventional glass ionomer cement (C-GIC) and a silver-reinforced GIC (S-GIC) variant is of interest. Ten specimens of both C-GIC (GC Fuji II, Japan) and S-GIC (Riva Silver, SDI, Australia) were fabricated for the evaluation of compressive strength, and an identical number of samples were created for the examination of tensile strength. These specimens were then tested using a universal testing apparatus. The results exhibited that both the compressive and diametral tensile strengths were significantly greater for the S-GIC cement in comparison to the C-GIC, with a notable p-value of 0.001. The findings suggest that S-GIC may be considered a viable alternative to conventional GIC.

16.
J Phys Chem A ; 128(24): 4867-4875, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38850256

RESUMO

In the atmosphere, the photodissociation of HONO is a significant source of OH radicals after ozone. In the present study, using Born-Oppenheimer molecular dynamics, we showed that HONO can dissociate on ice and water surfaces without light. In addition, the dissociation time of HONO is found to be much less on the ice surface compared to the same time on the water droplets.

17.
Polymers (Basel) ; 16(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891408

RESUMO

Ablative composites serve as sacrificial materials, protecting underlying materials from high-temperature environments by endothermic reactions. These materials undergo various phenomena, including thermal degradation, pyrolysis, gas generation, char formation, erosion, gas flow, and different modes of heat transfer (such as conduction, convection, and radiation), all stemming from these endothermic reactions. These phenomena synergize to form a protective layer over the underlying materials. Carbon, with its superb mechanical properties and various available forms, is highlighted, alongside phenolics known for good adhesion and fabric ability and elastomers valued for flexibility and resilience. This study focuses on recent advancements in carbon-and-phenolic and carbon-and-elastomeric composites, considering factors such as erosion speed; high-temperature resistance; tensile, bending, and compressive strength; fiber-matrix interaction; and char formation. Various authors' calculations regarding the percentage reduction in linear ablation rate (LAR) and mass ablation rate (MAR) are discussed. These analyses inform potential advancements in the field of carbon/phenolic and carbon/elastomeric ablative composites.

18.
Environ Sci Pollut Res Int ; 31(28): 40851-40872, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837030

RESUMO

The possible impact of antivirals on ecosystems and the emergence of antiviral resistance are the reasons for concern about their environmental release. Consequently, there has been a significant increase in curiosity regarding their presence in both organic and synthetic systems in recent years. The primary objective of this review is to address the void of information regarding the global presence of antiviral drugs in both wastewater and natural water sources. Photocatalytic degradation of pollutants is an eco-friendly, cost-effective method that effectively addresses environmental degradation. The development of efficient photocatalysts remains a significant issue in accelerating the degradation of pollutants, especially when employing solar light. Thus, the development of Z-scheme and S-scheme semiconductor heterojunctions has emerged as a viable method to improve light absorption and enhance the redox capability of photocatalysts. The principles of Z-scheme and S-scheme are reviewed extensively. The degradation route and occurrence of antiviral are discussed briefly. Finally, a short preview of the degradation of antiviral using Z-scheme and S-scheme is also highlighted.


Assuntos
Antivirais , Antivirais/química , Catálise , Poluentes Químicos da Água/química , Águas Residuárias/química
19.
Mol Cell Biol ; : 1-12, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828991

RESUMO

The protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP-1) plays an important role in modulating glucose and lipid homeostasis. We previously suggested a potential role of SHP-1 in the regulation of peroxisome proliferator-activated receptor γ2 (PPARγ2) expression and activity but the mechanisms were unexplored. PPARγ2 is the master regulator of adipogenesis, but how its activity is regulated by tyrosine phosphorylation is largely unknown. Here, we found that SHP-1 binds to PPARγ2 primarily via its N-terminal SH2-domain. We confirmed the phosphorylation of PPARγ2 on tyrosine-residue 78 (Y78), which was reduced by SHP-1 in vitro resulting in decreased PPARγ2 stability. Loss of SHP-1 led to elevated, agonist-induced expression of the classical PPARγ2 targets FABP4 and CD36, concomitant with increased lipid content in cells expressing PPARγ2, an effect blunted by abrogation of PPARγ2 phosphorylation. Collectively, we discovered that SHP-1 affects the stability of PPARγ2 through dephosphorylation thereby influencing adipogenesis.

20.
Food Chem Toxicol ; 189: 114747, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38768937

RESUMO

Chronic exposure to lead (Pb) induces neurodegenerative changes in animals and humans. Drugs with strong antioxidant properties are effective against Pb-mediated neurotoxicity. In a prior study, we identified 5,7-dihydroxy-3',4',5'-trimethoxyflavone (TMF) from Ocimum basilicum L. leaves as a potent antioxidant and neuroprotective compound. This research explores TMF's neuroprotective effects against Pb-induced brain toxicity in rats to establish it as a therapeutic agent. Rats received lead acetate (100 mg/kg, orally, once daily) for 30 days to induce brain injury, followed by TMF treatment (5 and 10 mg/kg, oral, once daily) 30 min later. Cognitive and motor functions were assessed using Morris Water Maze and horizontal bar tests. Lead, monoamine oxidase (MAO) A and B enzymes, reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), Tumor necrosis factor-alpha (TNF-α), and IL-6 levels were measured in the hippocampus and cerebellum. Pb exposure impaired cognitive and motor functions, increased Pb, TBARS, TNF-α, and IL-6 levels, and compromised MAO A & B and GSH levels. TMF reversed Pb-induced memory and motor deficits and normalized biochemical anomalies. TMF's neuroprotective effects against lead involve chelating, antioxidant, anti-inflammatory, and monoaminergic properties, suggesting its potential as a treatment for metal-induced brain injury.


Assuntos
Anti-Inflamatórios , Antioxidantes , Animais , Antioxidantes/farmacologia , Masculino , Ratos , Anti-Inflamatórios/farmacologia , Fármacos Neuroprotetores/farmacologia , Flavonas/farmacologia , Chumbo/toxicidade , Quelantes/farmacologia , Ratos Wistar , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/prevenção & controle , Glutationa/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos
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