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1.
Univ. salud ; 26(2): D16-D27, mayo-agosto 2024. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1553971

RESUMO

Introducción: La pandemia por COVID-19 ha afectado significativamente la calidad de los servicios de cuidado de la salud. Objetivo: Analizar los efectos en los atributos de la calidad en salud de los servicios de atención de enfermedades diferentes a la COVID-19 en Colombia, durante el periodo 2020-2022. Materiales y métodos: Se analizaron 24 artículos de alcance nacional y otros específicos de departamentos como Antioquia, Córdoba, Santander y Cundinamarca. Resultados: La pandemia por COVID-19 impactó la calidad de los servicios en la atención de enfermedades como cáncer, accidentes cerebrovasculares y de eventos como la interrupción voluntaria del embarazo. Conclusión: La calidad de la salud se vio afectada en todas sus dimensiones durante las fases de la pandemia, especialmente en la población con enfermedades crónicas y relacionadas con la salud infantil y materna. Además, se destacaron respuestas como el uso de la telemedicina y de la atención domiciliaria para contribuir a la calidad de la salud en Colombia.


Introduction: The COVID-19 pandemic has significantly affected the quality of health care services. Objective: To analyze the effects of COVID-19 on the quality of health care services focused on treating diseases other than COVID-19 in Colombia during the 2020-2022 period. Materials and methods: 24 articles were analyzed, which included some studies focused on national issues and others specific to the departments of Antioquia, Cordoba, Santander, and Cundinamarca. Results: The COVID-19 pandemic affected the quality of health services caring for diseases such as cancer, strokes, and critical circumstances like voluntary termination of pregnancy. Conclusion: All dimensions of health care were affected during the pandemic, especially impacting populations with chronic diseases and diseases related to child and maternal health. It is important to highlight that telemedicine and home care contributed to improving the quality of health in Colombia.


Introdução: A pandemia de COVID-19 afetou significativamente a qualidade dos serviços de saúde. Objetivo: Analisar os efeitos da COVID-19 nos atributos de qualidade em saúde dos serviços de atenção a outras doenças além da COVID-19 na Colômbia, durante o período 2020-2022. Materiais e métodos: foram analisados 24 artigos de âmbito nacional e outros específicos de departamentos como Antioquia, Córdoba, Santander e Cundinamarca. Resultados: A pandemia da COVID-19 impactou a qualidade dos serviços no cuidado de doenças como câncer, acidente vascular cerebral e eventos como a interrupção voluntária da gravidez. Conclusão: A qualidade da saúde foi afetada em todas as suas dimensões durante as fases da pandemia, especialmente na população com doenças crônicas e doenças relacionadas à saúde infantil e materna. Além disso, foram destacadas respostas como o uso da telemedicina e do atendimento domiciliar para contribuir para a qualidade da saúde na Colômbia.


Assuntos
Humanos , Masculino , Feminino , Atenção à Saúde , Acessibilidade aos Serviços de Saúde
2.
Rev. neurol. (Ed. impr.) ; 78(9)1-15 may 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-CR-366

RESUMO

Introducción Presentamos un paciente diagnosticado de narcolepsia de tipo 1 que desarrolló una encefalitis autoinmune posvacunal y/o tras una infección por el SARS-CoV-2. Caso clínico Paciente de 23 años que es remitido a urgencias por trastorno del lenguaje y temblor, acompañados de cefalea, trastorno del comportamiento, disfunción autonómica, crisis focal motora derecha y letargo. El paciente había sido vacunado siete semanas antes con la primera dosis de la vacuna Moderna (ARN mensajero) y, cuatro semanas después de la vacunación, presentó una infección por el SARS-CoV-2 con test de antígenos positivo. Resultados La exploración neurológica mostró un nivel de conciencia normal y una afasia mixta de predominio motor (campimetría, pares craneales, reflejos y sensibilidad normales). El test de reacción en cadena de la polimerasa para la COVID-19 fue negativo. En el líquido cefalorraquídeo se apreció una linfocitosis y proteínas elevadas. Los cultivos para hongos y bacterias fueron negativos. Los anticuerpos onconeuronales fueron normales. La resonancia magnética cerebral mostró en la secuencia de difusión una restricción con afectación cortical y morfología giral en el hemisferio cerebral izquierdo, y distribución parcheada con afectación de lóbulo frontal y temporal izquierdos. Una tomografía axial computarizada de tórax-abdomen-pelvis fue normal, al igual que las ecografías pélvica y escrotal. Al paciente se le trató con plasmaféresis y corticoides, con buena evolución clínica y resolución casi completa de las anomalías en la neuroimagen. Conclusión Se trata de un paciente con narcolepsia de tipo 1 con criterios de encefalitis autoinmune de comienzo subagudo. La infección por el SARS-CoV-2 o la vacunación, o ambas, constituyen un riesgo para desarrollar una o más enfermedades autoinmunes con la edad –como sucede en este caso–, lo que permite comprender la implicación de procesos inmunomediados en la fisiopatología de estas enfermedades. (AU)


INTRODUCTION We present a narcolepsy type 1 patient that develop an autoimmune encephalitis post vaccine and/or a SARS-CoV-2 infection.CASE REPORTAt 23 years old, the patient was referred to the emergency room with difficult speaking, headache and tremor followed by changes in behavior, autonomic dysfunction, right focal motor seizure and lethargy. He has received seven weeks before mRNA-1273 (Moderna) vaccine followed by a SARS-CoV-2 infection four weeks after vaccination (positive antigen test).RESULTSThe neurological examination was normal (visual fields, cranial nerves, motor, sensory and reflexes). Nasopharyngeal swab polymerase chain reaction (PCR) testing for COVID-19 was negative. Cerebrospinalfluid (CSF) had highly elevated protein and lymphocytic pleocytosis. CSF bacterial and fungal cultures for viral infections were negative. Brain magnetic resonance imaging (MRI) showed no abnormality on the non-enhanced sequences but the diffusion weighted imaging showed restricted diffusion with high signal on the left hemisphere mainly in the cerebral cortex with a gyro morphology, patched distribution with involvement of the temporal and frontal lobes. Chest, abdomen and pelvis computed tomography; pelvic and scrotum ultrasound, showed no malignancy. Onconeural antibodies were negative. The patient was treated with plasmapheresis and corticosteroids with a good clinical outcome and near complete resolution of the MRI abnormalities. CONCLUSION. The patient fulfilled the diagnostic criteria for autoimmune encephalitis with subacute onset. COVID-19 infection and vaccination could constitute a risk in a patient with narcolepsy as in this case and, could help to provide better understanding of the implication of immune-mediated processes in the pathophysiology of the diseases. (AU)


Assuntos
Humanos , Adulto Jovem , Comorbidade , Doenças Autoimunes do Sistema Nervoso/diagnóstico por imagem , Vacinação/efeitos adversos , Narcolepsia
4.
Pak J Pharm Sci ; 37(2): 321-326, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38767099

RESUMO

Fatigue is a serious disturbance to human health, especially in people who have a severe disease such as cancer, or have been infected with COVID-19. Our research objective is to evaluate the anti-fatigue effect and mechanism of icariin through a mouse experimental model. Mice were treated with icariin for 30 days and anti-fatigue effects were evaluated by the weight-bearing swimming test, serum urea nitrogen test, lactic acid accumulation and clearance test in blood and the amount of liver glycogen. The protein expression levels of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1-α) in the skeletal muscle of mice in each group were measured by western blotting. Results showed that icariin prolonged the weight-bearing swimming time of animals, reduced the serum urea nitrogen level after exercise, decreased the blood lactic acid concentration after exercise and increased the liver glycogen content observably. Compared to that in the control group, icariin upregulated AMPK and PGC1-α expression in skeletal muscle. Icariin can improve fatigue resistance in mice and its mechanism may be through improving the AMPK/PGC-1α pathway in skeletal muscle to enhance energy synthesis, decreasing the accumulation of metabolites and slowing glycogen consumption and decomposition.


Assuntos
Nitrogênio da Ureia Sanguínea , Fadiga , Flavonoides , Ácido Láctico , Músculo Esquelético , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Animais , Flavonoides/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Camundongos , Masculino , Ácido Láctico/sangue , Ácido Láctico/metabolismo , Fadiga/tratamento farmacológico , Fadiga/metabolismo , Natação , Proteínas Quinases Ativadas por AMP/metabolismo , Glicogênio/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Glicogênio Hepático/metabolismo
5.
J Virol ; : e0003824, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767356

RESUMO

Recent progress on chimeric antigen receptor (CAR)-NK cells has shown promising results in treating CD19-positive lymphoid tumors with minimal toxicities [including graft versus host disease (GvHD) and cytokine release syndrome (CRS) in clinical trials. Nevertheless, the use of CAR-NK cells in combating viral infections has not yet been fully explored. Previous studies have shown that CAR-NK cells expressing S309 single-chain fragment variable (scFv), hereinafter S309-CAR-NK cells, can bind to SARS-CoV-2 wildtype pseudotyped virus (PV) and effectively kill cells expressing wild-type spike protein in vitro. In this study, we further demonstrate that the S309-CAR-NK cells can bind to different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants in vitro. We also show that S309-CAR-NK cells reduce virus loads in the NOD/SCID gamma (NSG) mice expressing the human angiotensin-converting enzyme 2 (hACE2) receptor challenged with SARS-CoV-2 wild-type (strain USA/WA1/2020). Our study demonstrates the potential use of S309-CAR-NK cells for inhibiting infection by SARS-CoV-2 and for the potential treatment of COVID-19 patients unresponsive to otherwise currently available therapeutics. IMPORTANCE: Chimeric antigen receptor (CAR)-NK cells can be "off-the-shelf" products that treat various diseases, including cancer, infections, and autoimmune diseases. In this study, we engineered natural killer (NK) cells to express S309 single-chain fragment variable (scFv), to target the Spike protein of SARS-CoV-2, hereinafter S309-CAR-NK cells. Our study shows that S309-CAR-NK cells are effective against different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants. The S309-CAR-NK cells can (i) directly bind to SARS-CoV-2 pseudotyped virus (PV), (ii) competitively bind to SARS-CoV-2 PV with 293T cells expressing the human angiotensin-converting enzyme 2 (hACE2) receptor (293T-hACE2 cells), (iii) specifically target and lyse A549 cells expressing the spike protein, and (iv) significantly reduce the viral loads of SARS-CoV-2 wild-type (strain USA/WA1/2020) in the lungs of NOD/SCID gamma (NSG) mice expressing hACE2 (hACE2-NSG mice). Altogether, the current study demonstrates the potential use of S309-CAR-NK immunotherapy as an alternative treatment for COVID-19 patients.

6.
Nat Commun ; 15(1): 3816, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769293

RESUMO

SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.


Assuntos
COVID-19 , Ferroptose , Pulmão , Mesocricetus , SARS-CoV-2 , COVID-19/virologia , COVID-19/metabolismo , COVID-19/patologia , Animais , Humanos , Masculino , Pulmão/patologia , Pulmão/virologia , Pulmão/metabolismo , SARS-CoV-2/fisiologia , Feminino , Ferro/metabolismo , Pessoa de Meia-Idade , Modelos Animais de Doenças , Idoso , Lesão Pulmonar/virologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Sobrecarga de Ferro/metabolismo , Adulto , Cricetinae
7.
BMC Bioinformatics ; 25(1): 197, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769505

RESUMO

BACKGROUND: CAR-T cell therapy represents a novel approach for the treatment of hematologic malignancies and solid tumors. However, its implementation is accompanied by the emergence of potentially life-threatening adverse events known as cytokine release syndrome (CRS). Given the escalating number of patients undergoing CAR-T therapy, there is an urgent need to develop predictive models for severe CRS occurrence to prevent it in advance. Currently, all existing models are based on decision trees whose accuracy is far from meeting our expectations, and there is a lack of deep learning models to predict the occurrence of severe CRS more accurately. RESULTS: We propose PrCRS, a deep learning prediction model based on U-net and Transformer. Given the limited data available for CAR-T patients, we employ transfer learning using data from COVID-19 patients. The comprehensive evaluation demonstrates the superiority of the PrCRS model over other state-of-the-art methods for predicting CRS occurrence. We propose six models to forecast the probability of severe CRS for patients with one, two, and three days in advance. Additionally, we present a strategy to convert the model's output into actual probabilities of severe CRS and provide corresponding predictions. CONCLUSIONS: Based on our findings, PrCRS effectively predicts both the likelihood and timing of severe CRS in patients, thereby facilitating expedited and precise patient assessment, thus making a significant contribution to medical research. There is little research on applying deep learning algorithms to predict CRS, and our study fills this gap. This makes our research more novel and significant. Our code is publicly available at https://github.com/wzy38828201/PrCRS . The website of our prediction platform is: http://prediction.unicar-therapy.com/index-en.html .


Assuntos
COVID-19 , Síndrome da Liberação de Citocina , Aprendizado Profundo , Imunoterapia Adotiva , Humanos , COVID-19/terapia , Síndrome da Liberação de Citocina/terapia , Síndrome da Liberação de Citocina/etiologia , Imunoterapia Adotiva/métodos , SARS-CoV-2 , Neoplasias/terapia
8.
Adv Food Nutr Res ; 109: 271-314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38777416

RESUMO

Viruses can cause many human diseases. Three types of human diseases caused by viruses are discussed in this chapter: infectious diseases, autoimmune diseases, and cancers. The infectious diseases included in this chapter include three respiratory tract diseases: influenza, COVID-19, and respiratory syncytial virus. In addition, the mosquito-borne dengue virus diseases are discussed. Vitamin D can reduce risk, severity, and mortality of the respiratory tract diseases and possibly for dengue virus. Many autoimmune diseases are initiated by the body's reaction to a viral infection. The protective role of vitamin D in Epstein-Barr virus-related diseases such as multiple sclerosis is discussed. There are a few cancers linked to viral infections. Such cancers include cervical cancer, head and neck cancers, Hodgkin's and non-Hodgkin's lymphoma, and liver cancer. Vitamin D plays an important role in reducing risk of cancer incidence and mortality, although not as strongly for viral-linked cancers as for other types of cancer.


Assuntos
Doenças Autoimunes , COVID-19 , Neoplasias , Viroses , Vitamina D , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Doenças Transmissíveis
9.
World Neurosurg X ; 23: 100387, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38746040

RESUMO

Objective: To describe clinicoradiological features and surgical outcomes in a series of nine patients with rhino-orbito-cerebral mucormycosis (ROCM) who presented with Pott's puffy tumor (ROCM-PPT). Methods: The records of nine patients with ROCM-PPT seen between March 2020 and December 2021 were analysed. Clinical features, radiology, histopathology, operative findings, management and outcome were noted. Frontal sinus pneumatisation and outflow tract configuration was compared between patients and controls with ROCM and no PPT. Results: ROCM-PPT was diagnosed in 9 of 284 (3.2 %) patients with ROCM seen during the study period. There were six (66.7 %) males and the median age was 54 (IQR 46-60) years. Eight (88.9 %) patients had diabetes mellitus and seven (77.8 %) had been COVID-19 positive. Radiological features of osteomyelitis, subperiosteal abscess formation and dural enhancement were seen in all patients. No significant differences in pneumatisation or frontal sinus outflow tract configuration were noted between patients and controls. All patients underwent a craniectomy with frontal bone debridement and frontal sinus exteriorisation. All patients were treated with anti-fungal agents for several months. All patients had symptomatic improvement at a median follow-up of 21 (IQR 18-23) months. Repeat CT/MRI scans showed disease regression/resolution in six out of eight (75 %) patients with follow-up imaging, and stable disease in two others. Conclusions: ROCM-PPT is a rare, delayed complication of mucormycosis that was seen in larger numbers during the recent COVID-19 pandemic. Aggressive debridement of osteomyelitic bone and antifungal therapy results in a good outcome.

10.
Front Genet ; 15: 1381917, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38746057

RESUMO

MicroRNAs (miRNAs) are promising biomarkers for the early detection of disease, and many miRNA-based diagnostic models have been constructed to distinguish patients and healthy individuals. To thoroughly utilize the miRNA-profiling data across different sequencing platforms or multiple centers, the models accounting the batch effects were demanded for the generalization of medical application. We conducted transcription factor (TF)-mediated miRNA-miRNA interaction network analysis and adopted the within-sample expression ratios of miRNA pairs as predictive markers. The ratio of the expression values between each miRNA pair turned out to be stable across multiple data sources. A genetic algorithm-based classifier was constructed to quantify risk scores of the probability of disease and discriminate disease states from normal states in discovery, with a validation dataset for COVID-19, renal cell carcinoma, and lung adenocarcinoma. The predictive models based on the expression ratio of interacting miRNA pairs demonstrated good performances in the discovery and validation datasets, and the classifier may be used accurately for the early detection of disease.

11.
Public Health Pract (Oxf) ; 7: 100497, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38746654

RESUMO

Objectives: This study aims to assess cancer patients' accessibility to healthcare services and perceived barriers during the COVID-19 pandemic in Khartoum state, aiming to explore the consequent impact on cancer patients. It also aims to determine the coping strategies used by patients to overcome these barriers. Study design: This is a retrospective analytical cross-sectional study. Methods: Data were collected from August 2020 to March 2021, with a sample size of 316 cancer patients. Systemic random sampling and SPSS version 25 were utilized for data collection and analysis. Results: The study found that 55.7 % of the surveyed cancer patients had experienced disruptions in accessing essential cancer healthcare services during the lockdown. The study identified the most common cancers as breast (19.7 %), gastrointestinal (19 %), and ovarian (11 %). Notable barriers included governmental travel restrictions (51.6 %), outpatient service closures (41.8 %), and high costs (27.8 %). Additionally, delayed treatment was directly associated with a 33.3 % fatality rate among the participants. Conclusions: This study highlights the considerable negative impact of the COVID-19 lockdown on cancer care in Sudan. Recommendations include a focus on telemedicine as an alternative form of patient consultation, the expansion of health insurance schemes to encompass cancer treatments, and strengthening healthcare infrastructure to facilitate cancer care during crises.

12.
Can Liver J ; 7(2): 286-290, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38746868

RESUMO

Background: Since 2018, British Columbia (BC) has recommended chronic hepatitis C (HCV) screening for those born between 1945 and 1964, with a provincial prevalence of 2.31%. Combining HCV and colorectal cancer (CRC) screening can facilitate specialist referrals and follow-up. We assessed HCV screening uptake among CRC screening patients following the release of BC's birth cohort guidelines and examined the COVID-19 pandemic's impact on HCV screening practices. Methods: A retrospective review was conducted on patients referred to Vancouver Coastal Health Authority's CRC screening program. Two groups, Cohort A (October-December 2019) and Cohort B (December 2021), were studied to identify pandemic-related changes. Data on demographics, liver disease history, hepatitis B or HIV co-infection rates, and initial anti-hepatitis C and ribonucleic acid (RNA) testing dates were collected. Statistical analyses were performed with Stata 15.1. Results: A total of 579 patients were referred for the CRC screening program, of whom 465 were born between 1945 and 1964 and were included in the study. Among the 348 patients in cohort A, 144 (41%, 95% CI 36%-47%) were screened for HCV infection. Of these, four (1.2%) were positive for anti-hepatitis C, and one patient had positive RNA levels. Similar proportions of screenings were observed in cohort B (47.8%, 95% CI 39%-57%). Of those with liver disease, 66% had been screened for HCV. Conclusion: Birth cohort screening for HCV has been underutilized in British Columbia. Combining HCV and CRC screening could provide a practical approach to linking patients to health care.

13.
Technol Health Care ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38759066

RESUMO

BACKGROUND: Spleen Epstein-Barr Virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (FDCS) is rare, and the imaging signs are unclear. The COVID-19 has been confirmed to be the cause of pneumonia and can cause a variety of diseases including myocarditis. However, it has not been reported to be the cause of the exacerbation or activation of EBV-positive inflammatory FDCS. OBJECTIVE: The objective is to extract the imaging features of EBV-positive inflammatory FDCS in the spleen and analyze the reasons for the special features of this case. METHODS: By analyzing the patient's treatment process and imaging examinations (A 77-year-old female was admitted to the hospital due to generalized discomfort and pain symptoms. When she was admitted to the hospital a year earlier with COVID-19 pneumonia, a chest CT scan showed that she had a splenic tumor. During this admission, CT scans showed two irregularly shaped and unevenly dense soft tissue density masses within the spleen, with uneven enhancement on contrast-enhanced im-aging within the solid components and along the edges. PET/CT scans revealed elevated glucose metabolism in the masses. Postoperative pathological diagnosis confirmed splenic EBV-positive inflammatory FDCS.), reading the literature, sorting out the disease cognitive process, epidemiology, and pathological data of EBV-positive inflammatory FDCS, we discussed the imaging manifestations and possible differential diagnosis of the disease. RESULTS: The patient was finally diagnosed with splenic EBV-positive inflammatory FDCS. CONCLUSIONS: Imaging features of EBV-positive inflammatory FDCS in the spleen include a high incidence of hemorrhage and necrosis, persistent moderate enhancement of the solid portion, a "capsular-like enhancement" structure at the tumor edge, and possibly active glucose metabolism with high Standardized Uptake Values (SUVs). COVID-19 infection and long-term COVID-19 sequelae may exacerbate and activate EBV-positive inflammatory FDCS in the spleen, and the mechanism remains to be further studied.

14.
Bioorg Med Chem ; 107: 117762, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759254

RESUMO

Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC50 value of 6.1 µmol/L, superior to the reference drug 5-fluorouracil (IC50: 9.63 ± 0.27 µmol/L). The structure-activity relationships (SARs) indicated that the introduction of -(4-NO2)Ph, 3-pyridyl, -(2-F)Ph, -(4-F)Ph, -(3-F)Ph, -(4-Cl)Ph, and -(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.

15.
Nat Rev Clin Oncol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760500

RESUMO

mRNA vaccines have been revolutionary in terms of their rapid development and prevention of SARS-CoV-2 infections during the COVID-19 pandemic, and this technology has considerable potential for application to the treatment of cancer. Compared with traditional cancer vaccines based on proteins or peptides, mRNA vaccines reconcile the needs for both personalization and commercialization in a manner that is unique to each patient but not beholden to their HLA haplotype. A further advantage of mRNA vaccines is the availability of engineering strategies to improve their stability while retaining immunogenicity, enabling the induction of complementary innate and adaptive immune responses. Thus far, no mRNA-based cancer vaccines have received regulatory approval, although several phase I-II trials have yielded promising results, including in historically poorly immunogenic tumours. Furthermore, many early phase trials testing a wide range of vaccine designs are currently ongoing. In this Review, we describe the advantages of cancer mRNA vaccines and advances in clinical trials using both cell-based and nanoparticle-based delivery methods, with discussions of future combinations and iterations that might optimize the activity of these agents.

16.
Mol Ther ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702886

RESUMO

In the rapidly evolving landscape of medical research, the emergence of RNA-based therapeutics is paradigm shifting. It is mainly driven by the molecular adaptability and capacity to provide precision in targeting. The coronavirus disease 2019 pandemic crisis underscored the effectiveness of the mRNA therapeutic development platform and brought it to the forefront of RNA-based interventions. These RNA-based therapeutic approaches can reshape gene expression, manipulate cellular functions, and correct the aberrant molecular processes underlying various diseases. The new technologies hold the potential to engineer and deliver tailored therapeutic agents to tackle genetic disorders, cancers, and infectious diseases in a highly personalized and precisely tuned manner. The review discusses the most recent advancements in the field of mRNA therapeutics for cancer treatment, with a focus on the features of the most utilized RNA-based therapeutic interventions, current pre-clinical and clinical developments, and the remaining challenges in delivery strategies, effectiveness, and safety considerations.

17.
JAMA Netw Open ; 7(5): e2411076, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38743424

RESUMO

Importance: Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is underused. Identifying potentially modifiable factors to address barriers in HCC surveillance is critical to improve patient outcomes. Objective: To evaluate clinician-level factors contributing to underuse of HCC surveillance in patients with cirrhosis. Design, Setting, and Participants: This survey study included primary care clinicians (PCCs) and gastroenterology and hepatology clinicians at 5 safety-net health systems in the US. Clinicians were surveyed from March 15 to September 15, 2023, to assess knowledge, attitudes, beliefs, perceived barriers, and COVID-19-related disruptions in HCC surveillance in patients with cirrhosis. Data were analyzed from October to November 2023. Main Outcome and Measures: HCC surveillance knowledge was assessed with 6 questions querying the respondent's ability to correctly identify appropriate use of HCC surveillance. Attitudes, perceived barriers, and beliefs regarding HCC surveillance and perceived impact of the COVID-19 pandemic-related disruptions with HCC surveillance were assessed with a series of statements using a 4-point Likert scale and compared PCCs and gastroenterology and hepatology clinicians. Results: Overall, 347 of 1362 clinicians responded to the survey (25.5% response rate), among whom 142 of 237 (59.9%) were PCCs, 48 of 237 (20.3%) gastroenterology and hepatology, 190 of 236 (80.5%) were doctors of medicine and doctors of osteopathic medicine, and 46 of 236 (19.5%) were advanced practice clinicians. On HCC knowledge assessment, 144 of 270 (53.3%) scored 5 or more of 6 questions correctly, 37 of 48 (77.1%) among gastroenterology and hepatology vs 65 of 142 (45.8%) among PCCs (P < .001). Those with higher HCC knowledge scores were less likely to report barriers to HCC surveillance. PCCs were more likely to report inadequate time to discuss HCC surveillance (37 of 139 [26.6%] vs 2 of 48 [4.2%]; P = .001), difficulty identifying patients with cirrhosis (82 of 141 [58.2%] vs 5 of 48 [10.4%]; P < .001), and were not up-to-date with HCC surveillance guidelines (87 of 139 [62.6%] vs 5 of 48 [10.4%]; P < .001) compared with gastroenterology and hepatology clinicians. While most acknowledged delays during the COVID-19 pandemic, 62 of 136 PCCs (45.6%) and 27 of 45 gastroenterology and hepatology clinicians (60.0%) reported that patients with cirrhosis could currently complete HCC surveillance without delays. Conclusions and Relevance: In this survey study, important gaps in knowledge and perceived barriers to HCC surveillance were identified. Effective delivery of HCC education to PCCs and health system-level interventions must be pursued in parallel to address the complex barriers affecting suboptimal HCC surveillance in patients with cirrhosis.


Assuntos
COVID-19 , Carcinoma Hepatocelular , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/epidemiologia , COVID-19/epidemiologia , Masculino , Feminino , SARS-CoV-2 , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto , Médicos de Atenção Primária/estatística & dados numéricos , Cirrose Hepática/epidemiologia , Atitude do Pessoal de Saúde , Competência Clínica/estatística & dados numéricos
18.
World J Oncol ; 15(3): 382-393, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751704

RESUMO

Multiple factors have engaged in the progression of thyroid cancer (TC). Recent studies have shown that viral infection can be a critical factor in the pathogenesis of TC. Viruses, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may play an essential role in the occurrence, development, and even prognosis in TC. This review mainly explored the potential role of viral infection in the progress of TC. The possible mechanisms could be recognizing the host cell, binding to the receptors, affecting oncogenes levels, releasing viral products to shape a beneficial environment, interacting with immune cells to induce immune evasion, and altering the pituitary-thyroid axis. Thus, comprehensive knowledge may provide insights into finding molecular targets for diagnosing and treating virus-related TC.

19.
Iran J Med Sci ; 49(5): 322-331, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38751871

RESUMO

Background: Cytokine release syndrome (CRS) is the leading cause of mortality in advanced stages of coronavirus patients. This study examined the prophylactic effects of fraxin, quercetin, and a combination of fraxin+quercetin (FQ) on lipopolysaccharide-induced mice. Methods: Sixty mice were divided into six groups (n=10) as follows: control, LPS only, fraxin (120 mg/Kg), quercetin (100 mg/Kg), dexamethasone (5 mg/Kg), and FQ. All treatments were administered intraperitoneally (IP) one hour before induction by LPS (5 mg/Kg) IP injection. Twenty-four hours later, the mice were euthanized. Interleukin one beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were quantified using an enzyme-linked immunosorbent assay (ELISA), and lung and kidney tissues were examined for histopathological alterations. This study was conducted at Al-Nahrain University, Baghdad, Iraq, in 2022. Results: FQ reduced IL-1ß (P<0.001). All treatments significantly suppressed IL-6, fraxin, quercetin, dexamethasone, and FQ, all with P<0.001. The TNF-α level was reduced more with dexamethasone (P<0.001) and quercetin (P<0.001). Histopathological scores were significantly reduced mainly by quercetin and FQ in the lungs with scores of 12.30±0.20 (P=0.093), and 15.70±0.20 (P=0.531), respectively. The scores were 13±0.26 (P=0.074) and 15±0.26 (P=0.222) for quercetin and FQ in the kidneys, respectively. Conclusion: All used treatments reduced proinflammatory cytokine levels and protected against LPS-induced tissue damage.


Assuntos
Síndrome da Liberação de Citocina , Lipopolissacarídeos , Quercetina , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Camundongos , Síndrome da Liberação de Citocina/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Tratamento Farmacológico da COVID-19 , Masculino , COVID-19 , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Interleucina-6/sangue , Interleucina-6/análise , Citocinas/efeitos dos fármacos , Interleucina-1beta , Fator de Necrose Tumoral alfa , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologia , Cumarínicos
20.
Front Med (Lausanne) ; 11: 1346888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751976

RESUMO

Background: Clinical signs of dysphagia, pancreatic achalasia, and esophagitis have been reported in patients with COVID-19. However, the causal relationship between COVID-19 and esophageal diseases is not clear. Therefore, we utilized Mendelian randomization to explore the potential association between COVID-19 and esophageal diseases. Methods: The summary statistics for a Genome-wide association study (GWAS) were obtained from The COVID-19 Host Genetics Initiative, encompassing four types of COVID-19 as exposure: severe COVID-19, hospitalized COVID-19 versus ambulatory COVID-19, hospitalized COVID-19 versus uninfected, and confirmed COVID-19. Additionally, summary statistics for ten esophageal diseases as outcomes were sourced from the GWAS Catalog and FinnGen databases. Univariate Mendelian randomization (MR) analysis was utilized to thoroughly investigate and validate the potential causal association between COVID-19 and various esophageal conditions, including esophageal varices, Barrett's esophagus, esophagitis, esophageal obstruction, esophageal ulcer, esophageal perforation, gastroesophageal reflux, congenital esophageal malformations, benign esophageal tumors, and esophageal adenocarcinoma. Results: An inverse variance-weighted (IVW) model was utilized for univariate Mendelian randomization (MR) analysis, which revealed that genetic liability in patients with confirmed COVID-19 was associated with esophageal obstruction (OR [95% CI]: 0.5275458 [0.2822400-0.9860563]; p-value = 0.0450699). Furthermore, a suggestive causal association was found between genetic liability and a reduced risk of benign esophageal tumors (OR [95% CI]: 0.2715453 [0.09368493-0.7870724]; p-value = 0.0163510), but with a suggestively increased risk of congenital esophageal malformations (OR [95% CI]: 6.959561 [1.1955828-40.51204]; p-value = 0.03086835). Additionally, genetic liability in hospitalized COVID-19 patients, compared to non-hospitalized COVID-19 patients, was suggestively associated with an increased risk of esophagitis (OR [95% CI]: 1.443859 [1.0890568-1.914252]; p-value = 0.01068201). The reliability of these causal findings is supported by Cochran's Q statistic and the MR-Egger intercept test. Conclusion: The results of this study suggest the existence of a causal relationship between COVID-19 and esophageal diseases, highlighting differing risk effects of COVID-19 on distinct esophageal conditions.

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