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1.
Cell Biochem Biophys ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744782

RESUMO

The treatment of cancer often leads to a range of adverse effects. Encapsulating drugs can mitigate these effects and enhance drug efficacy by enabling a controlled release at the site of interest. This study details the successful synthesis of zinc oxide nanoparticles (ZnONPs) through the precipitation of Zn(NO3)2·6H2O with KOH. A Pd(II) complex drug was synthesized from a Schiff base ligand derived from 2-hydroxybenzohydrazide and (E)-1-(2-(p-tolyl)hydrazono)propan-2-one using potassium tetrachloropalladate(II). This complex was subsequently incorporated into ZnONPs. Characterization of the resulting compounds was performed using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta Potential, Fourier Transform Infrared (FTIR) Spectroscopy, and UV-visible spectroscopy. TEM imaging revealed particle sizes of 160.69 ± 4.74 nm for ZnONPs and 185.28 ± 2.3 nm for the Pd(II) complex-encapsulated ZnONPs. The Zeta potential values were 6.53 mV for ZnONPs and 7.36 mV for Pd(II) complex-encapsulated ZnONPs. UV-visible spectroscopy showed an absorption peak at 360 nm for ZnONPs, while the Pd(II) complex-encapsulated ZnONPs exhibited a peak at 410 nm. FTIR analysis indicated the presence of the Pd(II) complex within the ZnONPs, as evidenced by a consistent Zn-O vibrational band at 832 cm-1 and a shift in another peak from 460 to 413 cm-1. Additionally, the detection of a C = N stretching vibration at 1548 cm-1 and a carbonyl stretch at 1626 cm-1 was observed. The Encapsulation Efficiency (E.E.) of the Pd(II) complex was 97.2%. A drug release experiment conducted at pH 7 showed a steady-state release pattern after 16 h, with a cumulative release of 44.3%. The cytotoxic effects of the Pd(II) complex and its encapsulated form in ZnONPs on the MCF-7 cell line were assessed via MTT test. The Pd(II) complex encapsulated within ZnONPs exhibited decreased toxicity relative to the unencapsulated drug, as evidenced by a higher IC50 value of 418.5 µg/ml. This suggests that the encapsulation facilitates a sustained release, which allows for targeted accumulation within cells. The elevated IC50 value indicates that the drug delivery system may be engineered to modulate the release of the drug in a more controlled manner, potentially resulting in a prolonged release profile rather than an immediate therapeutic impact.

2.
J Orofac Orthop ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748283

RESUMO

OBJECTIVES: This study aimed to analyze the global scholarly production of articles related to temporary anchorage devices (TADs) from 1998-2023 in peer-reviewed dental journals indexed in the Web of Science. MATERIALS AND METHODS: A database of TADs-related articles was created via a Web of Sciences structured search. The bibliometric characteristics of the studies, including the number of citations, publication year, journal title, journal impact factor (IF), authorship, contributing institutions and countries, thematic field, and study design, were extracted. Keyword co-occurrence network analyses and the correlation between the number of citations and the article age, journal IF, and journal quartile of each article were performed. RESULTS: The top 50 cited articles were published from 1999-2016, and the total number of citations ranged from 82-602, with 160.36 citations/paper on average. Most of the articles originated from Japan (n = 12), with the most remarkable contributions from Nihon and Okayama Universities, Japan (n = 5, each). The American Journal of Orthodontics and Dentofacial Orthopedics had the most cited articles, with 196.57 citations/paper on average. A significant positive correlation occurred between the number of citations and publication age (rho = 0.392, P = 0.005). CONCLUSION: Our scientometric analysis reported the characteristics of TADs-related articles published over 25 years. Most highly-cited articles were published between 2005 and 2008. The positive correlation between articles' publication date and the number of citations might impact the top 50 within the next 5-10 years.

3.
J Family Med Prim Care ; 13(3): 903-910, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38736817

RESUMO

Background: Khat has a stimulating and addictive effect and can induce consequences on the health and socioeconomic status of khat chewers. Objectives: This study aims to assess knowledge, attitude, and practice of khat chewing among parents in Jazan and its consequential effect on their children. Methods: This cross-sectional investigation was conducted in the Jazan region of Saudi Arabia. Data was collected via a web-based, self-administered questionnaire measuring demographics, knowledge, attitudes, and practices concerning khat chewing. The Chi-square test or Fisher's exact test was used to assess factors associated with khat chewing among parents and its consequential effect on their children. Results: A total of 724 parents were included. The sample had an overall good knowledge about the health hazards of khat chewing and an attitude against khat chewing. Nonetheless, the number of parents who reported that they had ever tried khat chewing was 200 (27.6%) and 106 parents (14.6%) confirmed that their children were khat chewers. Additionally, 98 (13.5%) parents declared that they practiced khat chewing in front of their children. Higher frequencies of parents who reported providing khat to their children were identified among parents with higher attitude levels that favor khat chewing (P value = 0.04). Conclusions: Efforts should be made to develop targeted preventive and educational strategies to reduce khat chewing among parents who have favorable attitudes toward khat chewing.

4.
Clin Cosmet Investig Dent ; 16: 115-125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736868

RESUMO

Background/Purpose: Whether YouTube videos contain precise and adequate information on certain orthodontic procedures remains unclear. This study aimed to investigate the content and quality of YouTube videos on orthodontic elastics and identify the predictors of high-level content YouTube videos. Materials and Methods: Two hundred YouTube videos were screened for eligibility, and after applying the inclusion criteria, 133 videos were excluded. Student's t-test was used to compare the characteristics, quality parameters, and total content of the low-level and high-level content videos. Chi-square or Fisher's exact tests were implemented to identify the source and content element differences across low-level and high-level content videos. Pearson's correlation coefficients were used to determine the relationship between the total content score, video information and quality index (VIQI), and YouTube characteristics. Stepwise linear multiple regressions with forward selection were used to test the association of the YouTube characteristics and VIQI with the total content score. Results: Among 67 included videos, only 19.4% of videos were classified as high-level content videos. High-level content videos had significantly higher mean number of likes (MD = 4041.7; SD = 4680.7; P-value=0.0068), VIQI score (MD = 4.17; SD = 4.87; P-value=0.0073), and total content score (MD = 4.04; SD = 1.23; P-value=<0.0001). The adjusted linear regression model demonstrated a significant association between the total content score and VIQI, where 1 unit increase in the VIQI was significantly associated with a 0.16 increase in the total content score (B = 0.16; standard error [SE]=0.04; P = 0.0003). Further, a significant association was observed between the total content score and video duration, where 1 minute increase in the video duration was significantly associated with a 0.15 increase in the total content score (B = 0.15; SE = 0.05; P = 0.008). Conclusion: This study demonstrated that YouTube content quality concerning orthodontic elastics is poor. Thus, future implementation of online visual content provided by certified orthodontists will ensure accurate and thorough information delivery.

5.
Front Neurol ; 15: 1376439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737347

RESUMO

Background: Magnetic resonance diffusion-weighted imaging (DWI) is the most sensitive modality for ischemic stroke diagnosis. However, DWI may fail to detect ischemic lesions in a proportion of patients. Methods: Following PRISMA statement, a systematic search of Medline, Embase, and Web of Science was conducted until January 3, 2024. The inclusion was confined to English literature with sufficient reporting. Proportions of DWI-negative ischemic stroke were pooled. For binary variables, odds ratios (ORs) were computed using the random-effects model. Results: Fourteen studies constituting 16,268 patients with a clinical diagnosis of ischemic stroke and available DWI findings were included. Intravenous thrombolysis (IVT) was administered to 19.6% of the DWI-negative group and 15.3% of the DWI-positive group. DWI-negative ischemic stroke was reported in 16% (95% CI: 10-24%; after sensitivity analysis: 11% [95% CI: 8-15%]) of stroke patients. Among minor stroke patients (National Institutes of Health Stroke scale [NIHSS] of 5 or less), 24% (95% CI 12-42%) had negative DWI findings. Predictors of DWI-negative scans included posterior circulation stroke, history of ischemic heart disease, prior stroke, or prior transient ischemic attack. Cardioembolic stroke (OR, 0.62, 95% CI: 0.41-0.93) and history of atrial fibrillation increased the likelihood of positive DWI findings (OR, 0.56, 95% CI: 0.45-0.71). Patients with DWI-negative ischemic stroke had higher odds of good functional outcomes (modified Rankin scale [mRS] of 0-1) (OR, 2.26; 95% CI: 1.03-4.92), lower odds of stroke recurrence (OR, 0.68; 95% CI: 0.48-0.96), and lower odds of severe disability or mortality (mRS of 3-6) (OR, 0.44; 95% CI: 0.34-0.57) compared to patients with positive DWI. Rates of symptomatic intracerebral hemorrhage after IVT were comparable between groups. Conclusion: DWI-negative findings were present in a significant proportion of ischemic stroke patients and may be utilized as a marker for favorable prognosis.

6.
Cureus ; 16(4): e57900, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725745

RESUMO

Extracorporeal shock wave lithotripsy (ESWL) is considered a safe, reliable, and non-invasive modality for kidney stone management. However, there are well-established complications related to ESWL documented in the literature in the form of renal and extrarenal complications. Skeletal complications related to ESWL are rarely recorded; as far as we know, there is only one documented case report of an ESWL-related burst vertebral fracture seen in an osteoporotic patient, diagnosed as granulomatous spondylitis. Here, we present a novel case of a transverse process fracture of the third lumbar vertebra related to ESWL in a young patient otherwise free from any medical illness.

7.
Digit Health ; 10: 20552076241249874, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726217

RESUMO

Automated epileptic seizure detection from ectroencephalogram (EEG) signals has attracted significant attention in the recent health informatics field. The serious brain condition known as epilepsy, which is characterized by recurrent seizures, is typically described as a sudden change in behavior caused by a momentary shift in the excessive electrical discharges in a group of brain cells, and EEG signal is primarily used in most cases to identify seizure to revitalize the close loop brain. The development of various deep learning (DL) algorithms for epileptic seizure diagnosis has been driven by the EEG's non-invasiveness and capacity to provide repetitive patterns of seizure-related electrophysiological information. Existing DL models, especially in clinical contexts where irregular and unordered structures of physiological recordings make it difficult to think of them as a matrix; this has been a key disadvantage to producing a consistent and appropriate diagnosis outcome due to EEG's low amplitude and nonstationary nature. Graph neural networks have drawn significant improvement by exploiting implicit information that is present in a brain anatomical system, whereas inter-acting nodes are connected by edges whose weights can be determined by either temporal associations or anatomical connections. Considering all these aspects, a novel hybrid framework is proposed for epileptic seizure detection by combined with a sequential graph convolutional network (SGCN) and deep recurrent neural network (DeepRNN). Here, DepRNN is developed by fusing a gated recurrent unit (GRU) with a traditional RNN; its key benefit is that it solves the vanishing gradient problem and achieve this hybrid framework greater sophistication. The line length feature, auto-covariance, auto-correlation, and periodogram are applied as a feature from the raw EEG signal and then grouped the resulting matrix into time-frequency domain as inputs for the SGCN to use for seizure classification. This model extracts both spatial and temporal information, resulting in improved accuracy, precision, and recall for seizure detection. Extensive experiments conducted on the CHB-MIT and TUH datasets showed that the SGCN-DeepRNN model outperforms other deep learning models for seizure detection, achieving an accuracy of 99.007%, with high sensitivity and specificity.

8.
Heliyon ; 10(9): e30440, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38742087

RESUMO

Sechium edule, commonly known as chayote is known for its low glycemic index, high fiber content, and rich nutritional profile, which suggests it may be beneficial for individuals with diabetes. While research specifically examining the impact of chayote on diabetes is limited, this study screened its biological impacts by using different biomarkers on streptozotocin-induced diabetic (STZ-ID) rats. The ethanolic extract of the Sechium edule fruits was assessed for different phytochemical, biochemical, and anti-diabetic properties. In the results, chayote extract had high phenolic and flavonoid contents respectively (39.25 ± 0.65 mg/mL and 12.16 ± 0.50 mg/mL). These high phenolic and flavonoid contents showed high implications on STZ-ID rats. Altogether 200 and 400 mg/kg of the extract considerably reduced the blood sugar level and enhanced the lipid profile of the STZ-ID rats. Additionally, they have decreased blood urea and serum creatinine levels. Besides, the levels of SGOT, SGPT, LDH, sodium, and potassium ions were significantly lowered after the administration period. More importantly, the electrocardiogram (ECG) parameters such as QT, RR, and QTc which were prolonged in the diabetic rats were downregulated after 35 days of administration of S. edule extract (400 mg/kg). And, the histological examination of the pancreas and kidney showed marked improvement in structural features of 200 and 400 mg/kg groups when compared to the diabetic control group. Where the increase in the glucose levels was positively correlated with QT, RR, and QTc (r2 = 0.76, r2 = 0.76, and r2 = 0.43) which means that ECG could significantly reflect the diabetes glucose levels. In conclusion, our findings showed that the fruit extract exerts a high potential to reduce artifacts secondary to diabetes which can be strongly suggested for diabetic candidates. However, there is a need to study the molecular mechanisms of the extract in combating artifacts secondary to diabetes in experimental animals.

9.
BMC Plant Biol ; 24(1): 412, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760706

RESUMO

Under greenhouse conditions, the resistance of 18 different genotypes of flax to powdery mildew was evaluated. To investigate genetic diversity and identify the molecular and biochemical markers linked to powdery mildew resistance in the tested genotypes, two molecular marker systems-start codon targeted (SCoT) and inter-simple sequence repeat (ISSR)-as well as a biochemical marker (protein profiles, antioxidant enzyme activity, and secondary metabolites) were used. Based on the results, the genotypes were classified into four categories: highly susceptible, susceptible, moderately susceptible, and moderately resistant. The genotypes differed significantly in powdery mildew severity: Polk had a severity of 92.03% and Leona had a severity of 18.10%. Compared to the other genotypes, the moderately resistant genotypes had higher levels of flavonoids, antioxidant enzymes, phenolics, and straw yield; nevertheless, their hydrogen peroxide and malondialdehyde levels were lower. Protein profiles revealed 93.75% polymorphism, although the ISSR marker displayed more polymorphism (78.4%) than the SCoT marker (59.7%). Specific molecular and biochemical markers associated with powdery mildew resistance were identified. The 18 genotypes of flax were divided into two major clusters by the dendrogram based on the combined data of molecular markers. The first main cluster included Leona (genotype number 7), considered moderate resistance to powdery mildew and a separate phenetic line. The second main cluster included the other 17 genotypes, which are grouped together in a sub-cluster. This means that, besides SCoT, ISSR markers can be a useful supplementary technique for molecular flax characterization and for identifying genetic associations between flax genotypes under powdery mildew infection.


Assuntos
Resistência à Doença , Linho , Variação Genética , Genótipo , Doenças das Plantas , Linho/genética , Linho/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Resistência à Doença/genética , Marcadores Genéticos , Ascomicetos/fisiologia , Biomarcadores/metabolismo
10.
Biomed Eng Online ; 23(1): 48, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760808

RESUMO

Monitoring of ingestive activities is critically important for managing the health and wellness of individuals with various health conditions, including the elderly, diabetics, and individuals seeking better weight control. Monitoring swallowing events can be an ideal surrogate for developing streamlined methods for effective monitoring and quantification of eating or drinking events. Swallowing is an essential process for maintaining life. This seemingly simple process is the result of coordinated actions of several muscles and nerves in a complex fashion. In this study, we introduce automated methods for the detection and quantification of various eating and drinking activities. Wireless surface electromyography (sEMG) was used to detect chewing and swallowing from sEMG signals obtained from the sternocleidomastoid muscle, in addition to signals obtained from a wrist-mounted IMU sensor. A total of 4675 swallows were collected from 55 participants in the study. Multiple methods were employed to estimate bolus volumes in the case of fluid intake, including regression and classification models. Among the tested models, neural networks-based regression achieved an R2 of 0.88 and a root mean squared error of 0.2 (minimum bolus volume was 10 ml). Convolutional neural networks-based classification (when considering each bolus volume as a separate class) achieved an accuracy of over 99% using random cross-validation and around 66% using cross-subject validation. Multiple classification methods were also used for solid bolus type detection, including SVM and decision trees (DT), which achieved an accuracy above 99% with random validation and above 94% in cross-subject validation. Finally, regression models with both random and cross-subject validation were used for estimating the solid bolus volume with an R2 value that approached 1 and root mean squared error values as low as 0.00037 (minimum solid bolus weight was 3 gm). These reported results lay the foundation for a cost-effective and non-invasive method for monitoring swallowing activities which can be extremely beneficial in managing various chronic health conditions, such as diabetes and obesity.


Assuntos
Deglutição , Eletromiografia , Humanos , Deglutição/fisiologia , Masculino , Feminino , Automação , Processamento de Sinais Assistido por Computador , Adulto , Redes Neurais de Computação , Tecnologia sem Fio
11.
Ann Thorac Surg ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38763220

RESUMO

BACKGROUND: Limited data exist regarding outcomes of delayed sternal closure (DSC) in adults with congenital heart disease (ACHD). METHODS: We reviewed 159 ACHD patients undergoing cardiac surgery 1993-2023, who required DSC (open sternum at the end of operation, n=112) or ESR (sternum emergently reopened, n=47). Regression models were performed to determine factors associated with outcomes. RESULTS: Of 112 patients undergoing DSC, 87 patients (77.6%) underwent DSC ≤4 days, and 25 patients (22.3%) >4 days. The most common operations were valve (n=35, 31.2%), aortic (n=33, 29.4%), and right ventricular outflow tract procedures (n=23, 20.5%). Median time to chest closure was 2 days (interquartile range 1, 5). Apart from gender, baseline characteristics were similar between DSC groups. A stepwise increase in early mortality was observed from DSC≤4 days to DSC>4 days (6.8% vs 32%), as well as incidence of early complications, except sternal infection. Risk factors associated with early mortality were age (p=0.02), DSC >4 days (p<0.001), hemodynamic indication (p=0.03), and single ventricle (p=0.02). On multivariable analysis, lower ejection fraction (p=0.04), hemodynamic indication (p=0.02), single ventricle (p=0.004), and diabetes mellitus (p=0.03) were predictors of prolonged time to chest closure. Amongst hospital survivors, there was no difference in late survival between patients undergoing DSC ≤4 days vs >4 days (p=0.48). CONCLUSIONS: Brief duration of DSC in ACHD patients is associated with low morbidity and mortality. Higher early mortality and complications were observed among patients who did not achieve chest closure within 4 days.

12.
J Chemother ; : 1-9, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764430

RESUMO

First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6 inhibitors has improved progression free survival. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy. We conducted a phase II randomized, open label, single centre clinical trial on patients with metastatic ER positive and HER 2 negative breast cancer. Eligible patients were randomized (1:1) to arm A: metronomic dose of capecitabine (500 mg/m2 BID) combined with letrozole (2.5 mg OD) or arm B: letrozole single agent. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized. This clinical trial is registered on ClinicalTrials.gov (MD-127-2019, NCT04571437). Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone (p = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm. Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.

13.
Gene ; : 148524, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735598

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50-70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and Insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using RT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects.

14.
Mol Divers ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727994

RESUMO

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC50 value of 0.294 µM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC50 value of 0.519 µM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future.

15.
Colloids Surf B Biointerfaces ; 238: 113930, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692174

RESUMO

Breast cancer is a wide-spread threat to the women's health. The drawbacks of conventional treatments necessitate the development of alternative strategies, where gene therapy has regained hope in achieving an efficient eradication of aggressive tumors. Monocarboxylate transporter 4 (MCT4) plays pivotal roles in the growth and survival of various tumors, which offers a promising target for treatment. In the present study, pH-responsive lipid nanoparticles (LNPs) based on the ionizable lipid,1,2-dioleoyl-3-dimethylammonium propane (DODAP), were designed for the delivery of siRNA targeting MCT4 gene to the breast cancer cells. Following multiple steps of characterization and optimization, the anticancer activities of the LNPs were assessed against an aggressive breast cancer cell line, 4T1, in comparison with a normal cell line, LX-2. The selection of the helper phospholipid to be incorporated into the LNPs had a dramatic impact on their gene delivery performance. The optimized LNPs enabled a powerful MCT4 silencing by ∼90 % at low siRNA concentrations, with a subsequent ∼80 % cytotoxicity to 4T1 cells. Meanwhile, the LNPs demonstrated a 5-fold higher affinity to the breast cancer cells versus the normal cells, in which they had a minimum effect. Moreover, the MCT4 knockdown by the treatment remodeled the cytokine profile in 4T1 cells, as evidenced by 90 % and ∼64 % reduction in the levels of TNF-α and IL-6; respectively. The findings of this study are promising for potential clinical applications. Furthermore, the simple and scalable delivery vector developed herein can serve as a breast cancer-targeting platform for the delivery of other RNA therapeutics.


Assuntos
Neoplasias da Mama , Citocinas , Transportadores de Ácidos Monocarboxílicos , Proteínas Musculares , Nanopartículas , RNA Interferente Pequeno , Microambiente Tumoral , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Nanopartículas/química , Humanos , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Feminino , Citocinas/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Animais , Camundongos , Técnicas de Silenciamento de Genes , Tamanho da Partícula , Concentração de Íons de Hidrogênio
16.
Life Sci Alliance ; 7(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38724194

RESUMO

NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a BRD4::NUTM1 fusion gene. Because the BRD4::NUTM1 gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the Brd4::Nutm1 fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, Brd4::Nutm1 can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.


Assuntos
Proteínas Nucleares , Proteínas de Fusão Oncogênica , Fatores de Transcrição , Animais , Camundongos , Proteínas de Fusão Oncogênica/genética , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Modelos Animais de Doenças , Carcinoma/genética , Carcinoma/metabolismo , Translocação Genética/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas que Contêm Bromodomínio
17.
Sci Rep ; 14(1): 10634, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724544

RESUMO

Chemical flooding through biopolymers acquires higher attention, especially in acidic reservoirs. This research focuses on the application of biopolymers in chemical flooding for enhanced oil recovery in acidic reservoirs, with a particular emphasis on modified chitosan. The modification process involved combining chitosan with vinyl/silane monomers via emulsion polymerization, followed by an assessment of its rheological behavior under simulated reservoir conditions, including salinity, temperature, pressure, and medium pH. Laboratory-scale flooding experiments were carried out using both the original and modified chitosan at conditions of 2200 psi, 135,000 ppm salinity, and 196° temperature. The study evaluated the impact of pressure on the rheological properties of both chitosan forms, finding that the modified composite was better suited to acidic environments, showing enhanced resistance to pressure effects with a significant increase in viscosity and an 11% improvement in oil recovery over the 5% achieved with the unmodified chitosan. Advanced modeling and simulation techniques, particularly using the tNavigator Simulator on the Bahariya formations in the Western Desert, were employed to further understand the polymer solution dynamics in reservoir contexts and to predict key petroleum engineering metrics. The simulation results underscored the effectiveness of the chitosan composite in increasing oil recovery rates, with the composite outperforming both its native counterpart and traditional water flooding, achieving a recovery factor of 48%, compared to 39% and 37% for native chitosan and water flooding, thereby demonstrating the potential benefits of chitosan composites in enhancing oil recovery operations.

18.
ACS Omega ; 9(19): 21204-21220, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38764688

RESUMO

Zeolite-A was synthesized successfully from kaolinite and hybridized with two species of biopolymers (chitosan (CH/Z) and ß-cyclodextrin (CD/Z)). The obtained hybridized forms were assessed as potential adsorbents of Congo red synthetic dye (CR) with enhanced affinities and elimination capacities. The synthesized CD/Z and CH/Z hybrids demonstrated uptake capacities of 223.6 and 208.7 mg/g, which are significantly higher than single-phase zeolite-A (140.3 mg/g). The integrated polymers change the surface area, surface reactivity, and number of free active receptors that are already present. The classic isotherm investigations validate Langmuir equilibrium behavior for ZA and Freundlich properties for CD/Z and CH/Z. The steric parameters validate a strong increase in the existing active receptors after the incorporation of CD (CD/Z) to be 98.1 mg/g as compared to 83 mg/g for CH/Z and 60.6 mg/g for ZA, which illustrate the detected uptake behaviors. Moreover, the CR dye was adsorbed as several molecules per single site, reflecting the vertical uptake of these molecules by multimolecular mechanisms. The energetic assessment, considering both Gaussian energies and adsorption energies (<40 kJ/mol), validates the dominant impact of the physical mechanism during the sequestration of CR (dipole binding interactions (2-29 kJ/mol) and hydrogen bonds (<30 kJ/mol)), in addition to the considerable effect of ion exchange processes. Based on the thermodynamic parameters, the CR molecules were adsorbed by exothermic and spontaneous reactions.

19.
Heliyon ; 10(10): e30929, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38765047

RESUMO

Among the range of severe plant diseases, bacterial soft rot caused by Erwinia carotovora is a significant threat to crops. This study aimed to examine the varying response patterns of distinct potato cultivars to the influence of E. carotovora. Furthermore, it seeks to highlight the potential role of salicylic acid (SA) and methyl jasmonate (MeJA) in stimulating the antioxidant defence system. We collected eight bacterial isolates from diseased and rotted tubers which were morphologically and physiologically identified as E. carotovora subsp. carotovora. We conducted a greenhouse experiment to analyse the antioxidant responses of three different potato cultivars (Diamont, Kara, and Karros) at various time intervals (2, 4, 6, 8, 12, and 24 h) after bacterial infection (hpi). We assessed the extent of disease damage by applying a foliar spray of 0.9 mM salicylic acid (SA) and 70 µM methyl jasmonate (MeJA). Inoculating with Ecc led to an increase in total phenolic levels, as well as the activities and gene expression of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POX) as time progressed. Additionally, the application of SA and MeJA resulted in a further increase relative to the diseased treatments. The Karros cultivar, unlike the Diamont and Kara cultivars, demonstrated the highest expression levels of PAL, PPO and POX through inoculation, reflecting its higher levels of activity and resistance. Furthermore, the genetic response of potato cultivars to infection at 0 hpi varied depending on their susceptibility. The examination of the rate of PAL activity upregulation following SA or MeJA stimulation clarifies the cultivars' susceptibility over time. In conclusion, the study identified E. carotovora subsp. carotovora as the most virulent isolate causing soft rot disease in potato tubers. It further revealed that the Karros cultivar displayed superior resistance with high activities and gene expression of PAL, PPO and POX, while the cv. Diamont exhibited sensitivity. Additionally, foliar exposure to SA and MeJA induced antioxidant responses, enhancing the potato plants' resistance against Ecc pathogenesis and overall plant defence.

20.
Orthop Rev (Pavia) ; 16: 91507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765295

RESUMO

Purpose: The number of total knee replacements (TKRs) performed per year has been increasing annually and it is estimated that by 2030 demand would reach 3.48 million procedures per year in the United States Of America. The prevalence of periprosthetic fractures (PPFs) around TKRs has followed this trend with incidences ranging from 0.3% to 3.5%. Distal femoral PPFs are associated with significant morbidity and mortality. When there is sufficient bone stock in the distal femur and a fracture pattern conducive to fixation, locking compression plating (LCP) and retrograde intramedullary nailing (RIMN) are commonly used fixation strategies. Conversely, in situations with loosening and deficient bone stock, a salvage procedure such as a distal femoral replacement is recognized as an alternative. This meta-analysis investigates the rates of non-union, re-operation, infection, and mortality for LCPs and RIMNs when performed for distal femoral PPFs fractures around TKRs. Method: A search was conducted to identify articles relevant to the management of distal femoral PPFs around TKRs in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Articles meeting the inclusion criteria were then assessed for methodological quality using the methodological items for non-randomised studies (MINORS) criteria. Articles were reviewed, and data were compiled into tables for analysis. Results: 10 articles met the inclusion criteria, reporting on 528 PPFs. The overall incidence of complications was: non-union 9.4%, re-operation 12.9%, infection 2.4%, and mortality 5.5%. This meta-analysis found no significant differences between RIMN and LCP in rates of non-union (9.2% vs 9.6%) re-operation (15.1% vs 11.3%), infection (2.1% vs 2.6%), and mortality (6.0% vs 5.2%), respectively. Conclusion: This meta-analysis demonstrated no significant difference in rates of non-union, re-operation, infection, and mortality between RIMN and LCP and both remain valid surgical treatment options.

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