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2.
Front Psychiatry ; 15: 1376567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764470

RESUMO

Background: Vaccine hesitancy is a significant global problem resulting from the interaction of multiple factors, including mental health factors. However, the association of COVID-19 vaccine hesitancy with mental health has not been well-examined, especially in Arab culture. This study aims to identify the correlation between anxiety/fear of COVID-19 and vaccine hesitancy among Saudi adults. Methods: An online-based survey was administered to 558 participants from all regions of Saudi Arabia using the snowball technique. However, this sample may not be representative of the Saudi adult population. Participants responded to the Questionnaire of Vaccine Hesitancy, the COVID-19-Anxiety Questionnaire (C-19-A), and the Fear of COVID-19 Scale (FCV-19S). Data were analyzed on vaccine uptake, vaccine hesitancy, coronavirus infection, and demographic variables. The predictive factors of vaccine hesitancy were examined in one model using multiple regression analysis by the Enter method (P= 0.05). Results: COVID-19 anxiety and fear have significant correlations with vaccine hesitancy (Phi=0.33, P=0.017; Phi=0.29, P=0.013, respectively). Anxiety and fear were higher among unhesitating participants (t =2.469, P=0.014; t=2.025, P=0.043, respectively). Participants who had previously been infected with coronavirus were more likely to be hesitant (X2 = 23.126, P=0.000). Participants who scored high in anxiety were more likely to be vaccinated (F=3.979, P=0.019) and have a secondary school or college education (F=4.903 P=0.002). COVID-19 anxiety, gender, and coronavirus infection significantly predicted vaccine hesitancy. Conclusion: Anxiety and fear of COVID-19 are among the most important factors correlated with vaccine hesitancy; unhesitant people are more likely to have anxiety and fear. COVID-19 anxiety significantly predicted vaccine hesitancy. We recommend integrating psychological care into vaccination plans to help increase the uptake rate during potential subsequent pandemics. Relevant intervention programs can be designed to help increase vaccine acceptance, deal with vaccine hesitancy, and relieve psychological symptoms during major pandemics. Psychologists can provide awareness messages, counselling seminars, online mentoring, or telemental health outreach.

3.
Biol Trace Elem Res ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758479

RESUMO

The success of arsenic trioxide (ATO) in acute promyelocytic leukemia has driven a plethora studies to investigate its efficacy in other malignancies. However, the inherent toxicity of ATO limits the expansion of its clinical applications. Such toxicity may be linked to ATO-induced metabolic derangements of endogenous substrates. Therefore, the primary objective of this study was to investigate the effect of ATO on the hepatic formation of arachidonic acid (AA) metabolites, hydroxyeicosatetraenoic acids (HETEs), as well as their most notable producing machinery, cytochrome P450 (CYP) enzymes. For this purpose, C57BL/6 mice were intraperitoneally injected with 8 mg/kg ATO for 6 and 24 h. Total RNA was extracted from harvested liver tissues for qPCR analysis of target genes. Hepatic microsomal proteins underwent incubation with AA, followed by identification/quantification of the produced HETEs. ATO downregulated Cyp2e1, while induced Cyp2j9 and most of Cyp4a and Cyp4f, and this has resulted in a significant increase in 17(S)-HETE and 18(R)-HETE, while significantly decreased 18(S)-HETE. Additionally, ATO induced Cyp4a10, Cyp4a14, Cyp4f13, Cyp4f16, and Cyp4f18, resulting in a significant elevation in 20-HETE formation. In conclusion, ATO altered hepatic AA metabolites formation through modulating the underlying network of CYP enzymes. Modifying the homeostatic production of bioactive AA metabolites, such as HETEs, may entail toxic events that can, at least partly, explain ATO-induced hepatotoxicity. Such modification can also compromise the overall body tolerability to ATO treatment in cancer patients.

4.
SAGE Open Med ; 12: 20503121241247458, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711467

RESUMO

Objectives: Epilepsy is a neurological disorder affecting more than 50 million human lives of all ages, its social, physical and psychological implications is of huge concern. The current study and as a continuation of epilepsy knowledge assessment projects conducted by our research team is aimed to assess the knowledge of healthcare workers regarding epilepsy first aid in Saudi Arabia. Methods: A cross-sectional questionnaire-based study was carried out from 2020 to 2021. Results: During the study period, 272 healthcare workers were recruited; participants were males and females from different nationalities in various Saudi Arabian cities, possess diverse qualifications, and belong to several healthcare-related professions. The question, "Did you witness an epileptic seizure"? was answered as "Yes" by 42% of participants, and in response to the question "If you know that this patient struggles during seizure attacks," 58% of respondents stated that they would not call an ambulance. Moreover, the question "Put something in his/her mouth to prevent tongue biting" was incorrectly answered as "Yes" by 42% of respondents, and the question "Try to catch him/her and stop his/her movement" in order to control the attack was answered "Yes" by 21% of respondents. Furthermore, almost 90% of healthcare participants do not know how to use the Vagus Nerve Stimulation device. The mean knowledge score among participants was 23.7; sex, as well as type of higher qualification obtained, was found to be significantly associated with the score of knowledge. Conclusion: Knowledge toward epilepsy and epilepsy first aid among healthcare workers in Saudi Arabia was found fragile. Further research is appreciated to support the current findings.

5.
PeerJ ; 12: e17374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756445

RESUMO

Background: An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods: The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman's correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results: The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = -0.460, p = 0.010), as well as gingival index (r = -0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion: Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.


Assuntos
Doença Celíaca , Dieta Livre de Glúten , Interleucina-17 , Interleucina-18 , Periodontite , Saliva , Humanos , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Interleucina-17/sangue , Interleucina-17/metabolismo , Interleucina-17/análise , Masculino , Feminino , Interleucina-18/sangue , Interleucina-18/análise , Interleucina-18/metabolismo , Saliva/química , Saliva/imunologia , Adulto , Periodontite/imunologia , Periodontite/metabolismo , Periodontite/sangue , Interleucina-1beta/sangue , Interleucina-1beta/análise , Interleucina-1beta/metabolismo , Estudos de Casos e Controles , Pessoa de Meia-Idade , Biomarcadores/sangue , Biomarcadores/análise , Adulto Jovem
6.
Saudi Dent J ; 36(4): 638-644, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38690396

RESUMO

Objective: To identify the potential factors that induce procedural errors during posterior proximal resin composite restorations placed by dental students. Materials and Methods: This retrospective study evaluated 803 bitewing radiographs of posterior proximal resin composite restorations placed by dental students at Imam Abdulrahman bin Faisal University. Atypical radiographic signs of failure were screened, and different patient-, operator-, and clinical-related factors were recorded. Chi-square test was used to examine the relationship between procedural errors and recorded factors. Stepwise adjusted logistic regression model was performed to identify predictors of procedural errors. Results: The most observed errors were internal gaps at the bonding interface and internal voids. Molars had 0.39 the risk of internal voids (odds ratio [OR] = 0.39; confidence interval [CI] = 0.25-0.60; P = <0.0001), 0.41 the risk of sharp angle (OR = 0.41; CI = 0.24-0.68; P = <0.001), and 0.57 the risk of open contact (OR = 0.57; CI = 0.34-0.97; P = 0.04) compared to premolars. Those who were >40 years of age had 1.79 the risk of overhang compared to younger patients (OR = 1.79; CI = 1.04-3.11; P = <0.04). First molars and premolars had 0.64 the risk of overhang compared to second molars and premolars (OR = 0.64; CI = 0.41-1.00; P = 0.04). Junior students had 1.97 the risk of internal gap compared to their senior counterparts (OR = 1.97; CI = 1.20-3.21; P = 0.008). Mesial restorations had 0.38 the risk of external gap compared to mesio-occluso-distal (MOD) restorations (OR = 0.38; CI = 0.19-0.78; P = 0.003). Restorations with a margin coronal to the cemento-enamel junction (CEJ) had 0.44 the risk of external gap compared to those restorations with a margin apical to the CEJ (OR = 0.44; CI = 0.29-0.66; P = <0.0001). Conclusion: Our findings suggested a higher incidence of procedural errors in restoring premolars and MOD cavity preparations. Therefore, it is crucial to enhance the comprehensiveness of laboratory training and expose students to diverse clinical scenarios and various techniques.

7.
BMC Nurs ; 23(1): 325, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741096

RESUMO

BACKGROUND: Nursing incivility, defined as disrespectful behaviour toward nurses, is increasingly recognized as a pressing issue that affects nurses' well-being and quality of care. However, research on the pathways linking incivility to outcomes is limited, especially in Saudi hospitals. METHODS: This cross-sectional study examined relationships between perceived nursing incivility, nurse stress, patient engagement, and health outcomes in four Saudi hospitals. Using validated scales, 289 nurses and 512 patients completed surveys on exposure to incivility, stress levels, activation, and medication adherence. The outcomes included readmissions at 30 days and satisfaction. RESULTS: More than two-thirds of nurses reported experiencing moderate to severe workplace incivility. Correlation and regression analyzes revealed that nursing incivility was positively associated with nursing stress. An inverse relationship was found between stress and patient participation. Serial mediation analysis illuminated a detrimental cascade, incivility contributing to increased nurse stress, subsequently diminishing patient engagement, ultimately worsening care quality. Conclusions The findings present robust evidence that nursing incivility has adverse ripple effects, directly impacting nurse well-being while indirectly affecting patient outcomes through reduced care involvement. Practical implications advocate for systemic interventions focused on constructive nursing cultures and patient empowerment to improve both healthcare provider conditions and quality of care. This study provides compelling information to inform policies and strategies to mitigate workplace mistreatment and encourage participation among nurses and patients to improve health outcomes.

8.
Front Oncol ; 14: 1288501, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559562

RESUMO

SKP2 (S-phase kinase-associated protein 2) is a member of the F-box family of substrate-recognition subunits in the SCF ubiquitin-protein ligase complexes. It is associated with ubiquitin-mediated degradation in the mammalian cell cycle components and other target proteins involved in cell cycle progression, signal transduction, and transcription. Being an oncogene in solid tumors and hematological malignancies, it is frequently associated with drug resistance and poor disease outcomes. In the current review, we discussed the novel role of SKP2 in different hematological malignancies. Further, we performed a limited in-silico analysis to establish the involvement of SKP2 in a few publicly available cancer datasets. Interestingly, our study identified Skp2 expression to be altered in a cancer-specific manner. While it was found to be overexpressed in several cancer types, few cancer showed a down-regulation in SKP2. Our review provides evidence for developing novel SKP2 inhibitors in hematological malignancies. We also investigated the effect of SKP2 status on survival and disease progression. In addition, the role of miRNA and its associated families in regulating Skp2 expression was explored. Subsequently, we predicted common miRNAs against Skp2 genes by using miRNA-predication tools. Finally, we discussed current approaches and future prospective approaches to target the Skp2 gene by using different drugs and miRNA-based therapeutics applications in translational research.

9.
Cureus ; 16(3): e55805, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586734

RESUMO

Introduction Teledentistry has emerged as a promising solution to enhance dental healthcare accessibility and quality. Understanding public awareness and attitudes toward teledentistry is crucial for its successful implementation, especially in regions like Saudi Arabia where digital health initiatives are rapidly expanding. This study aims to assess the level of awareness, attitudes, and perceptions toward teledentistry among the Saudi Arabian population, as well as examine the demographic factors influencing its acceptance. Methods A cross-sectional survey was conducted with 474 participants, employing a structured questionnaire to collect data on demographics, awareness, knowledge, perceptions, and attitudes toward teledentistry. Statistical analyses, including correlation and chi-square tests, were performed to analyze the data. Results The majority of respondents (64%) reported awareness of teledentistry, primarily through the Internet (44.5%) and healthcare providers (36.3%). The average self-assessed knowledge score was 3.04 out of 5, indicating moderate familiarity with teledentistry concepts. Attitudes toward teledentistry were generally positive, with 54% expressing belief in its effectiveness. However, a significant portion of the sample showed reluctance toward using teledentistry for routine dental check-ups, with only 45.1% showing willingness. High technological accessibility was reported, yet 55.9% of participants preferred traditional in-person consultations. Correlation analysis revealed a moderate positive relationship between knowledge and belief in effectiveness (r = 0.21), but a negligible correlation with willingness to use teledentistry (r = 0.016). A strong positive correlation was found between belief in effectiveness and willingness for routine check-ups (r = 0.673). Educational level significantly influenced teledentistry acceptance, with higher education correlating with greater receptiveness. Conclusion While there is a moderate level of awareness and a generally positive attitude toward teledentistry among the Saudi population, hesitance remains regarding its use for routine care. The findings highlight the need for educational initiatives to improve knowledge and perceptions of teledentistry, potentially enhancing its acceptance and integration into the healthcare system.

10.
BMC Med Imaging ; 24(1): 82, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589813

RESUMO

Breast Cancer is a significant global health challenge, particularly affecting women with higher mortality compared with other cancer types. Timely detection of such cancer types is crucial, and recent research, employing deep learning techniques, shows promise in earlier detection. The research focuses on the early detection of such tumors using mammogram images with deep-learning models. The paper utilized four public databases where a similar amount of 986 mammograms each for three classes (normal, benign, malignant) are taken for evaluation. Herein, three deep CNN models such as VGG-11, Inception v3, and ResNet50 are employed as base classifiers. The research adopts an ensemble method where the proposed approach makes use of the modified Gompertz function for building a fuzzy ranking of the base classification models and their decision scores are integrated in an adaptive manner for constructing the final prediction of results. The classification results of the proposed fuzzy ensemble approach outperform transfer learning models and other ensemble approaches such as weighted average and Sugeno integral techniques. The proposed ResNet50 ensemble network using the modified Gompertz function-based fuzzy ranking approach provides a superior classification accuracy of 98.986%.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Mamografia , Bases de Dados Factuais , Aprendizado de Máquina
11.
Pharmacol Res ; 203: 107167, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599470

RESUMO

Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased the overall survival and quality of life, there are no definite treatments for the advanced stages of this malady. Hence, understanding the diseases etiologies and the underlying molecular complexities, will usher in the development of innovative therapeutics. Recently, YAP/TAZ transcriptional regulation has been of immense interest due to their role in development, tissue homeostasis and oncogenic transformations. YAP/TAZ axis functions as coactivators within the Hippo signaling cascade, exerting pivotal influence on processes such as proliferation, regeneration, development, and tissue renewal. In cancer, YAP is overexpressed in multiple tumor types and is associated with cancer stem cell attributes, chemoresistance, and metastasis. Activation of YAP/TAZ mirrors the cellular "social" behavior, encompassing factors such as cell adhesion and the mechanical signals transmitted to the cell from tissue structure and the surrounding extracellular matrix. Therefore, it presents a significant vulnerability in the clogs of tumors that could provide a wide window of therapeutic effectiveness. Natural compounds have been utilized extensively as successful interventions in the management of diverse chronic illnesses, including cancer. Owing to their capacity to influence multiple genes and pathways, natural compounds exhibit significant potential either as adjuvant therapy or in combination with conventional treatment options. In this review, we delineate the signaling nexus of YAP/TAZ axis, and present natural compounds as an alternate strategy to target cancer.


Assuntos
Neoplasias , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP , Animais , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacos , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Proteínas de Sinalização YAP/metabolismo
12.
BMC Med Imaging ; 24(1): 100, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684964

RESUMO

PURPOSE: To detect the Marchiafava Bignami Disease (MBD) using a distinct deep learning technique. BACKGROUND: Advanced deep learning methods are becoming more crucial in contemporary medical diagnostics, particularly for detecting intricate and uncommon neurological illnesses such as MBD. This rare neurodegenerative disorder, sometimes associated with persistent alcoholism, is characterized by the loss of myelin or tissue death in the corpus callosum. It poses significant diagnostic difficulties owing to its infrequency and the subtle signs it exhibits in its first stages, both clinically and on radiological scans. METHODS: The novel method of Variational Autoencoders (VAEs) in conjunction with attention mechanisms is used to identify MBD peculiar diseases accurately. VAEs are well-known for their proficiency in unsupervised learning and anomaly detection. They excel at analyzing extensive brain imaging datasets to uncover subtle patterns and abnormalities that traditional diagnostic approaches may overlook, especially those related to specific diseases. The use of attention mechanisms enhances this technique, enabling the model to concentrate on the most crucial elements of the imaging data, similar to the discerning observation of a skilled radiologist. Thus, we utilized the VAE with attention mechanisms in this study to detect MBD. Such a combination enables the prompt identification of MBD and assists in formulating more customized and efficient treatment strategies. RESULTS: A significant breakthrough in this field is the creation of a VAE equipped with attention mechanisms, which has shown outstanding performance by achieving accuracy rates of over 90% in accurately differentiating MBD from other neurodegenerative disorders. CONCLUSION: This model, which underwent training using a diverse range of MRI images, has shown a notable level of sensitivity and specificity, significantly minimizing the frequency of false positive results and strengthening the confidence and dependability of these sophisticated automated diagnostic tools.


Assuntos
Aprendizado Profundo , Imageamento por Ressonância Magnética , Doença de Marchiafava-Bignami , Humanos , Doença de Marchiafava-Bignami/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Interpretação de Imagem Assistida por Computador/métodos , Sensibilidade e Especificidade
13.
Pediatr Transplant ; 28(3): e14715, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38553805

RESUMO

INTRODUCTION: Most kidneys from small pediatric donors are transplanted to adult recipients because of the perceived risk of surgical complications and graft thrombosis. In this study, we aim to demonstrate our favorable outcomes in transplanting pediatric kidneys from donors <15 k into pediatric recipients. METHODS: This study retrospectively analyzes the outcomes of seven pediatric recipients of en block kidney transplants from pediatric donors weighing <15 kg performed at King Fahad Specialist Hospital-Dammam from December 2014 to January 2018. Baseline characteristics of donors and recipients were collected. The incidences of surgical complication, immediate, and intermediate graft function were the primary outcomes. RESULTS: The study included seven recipients monitored for a mean duration of 6.86 ± 1.35. Donors' and recipients' mean weights were 7.4 ± 3.2 kg and 20.7 ± 9.2 kg, respectively. Ureteric stricture occurred in one patient. There was a substantial improvement of 1-year estimated glomerular filtration rate (eGFR) compared to the 1-week mark (106.7 ± 26.38 mL/min. 1.73 m2 vs. 63.7 ± 22.92 mL/min/1.73 m2, p = .0069). The observed improvement in renal function persisted at the 5-year mark and during the last follow-up, with eGFR of 70.3 ± 40.7 mL/min/1.73 m2, and 79.8 ± 30.8 mL/min/1.73 m2, respectively. There was also increase of 27.9% in the size of the en bloc kidney observed at the 6 months. CONCLUSION: In a specialized transplant center with highly skilled surgeons, the utilization of en bloc kidney transplant from donors weighing less than 15 kg is an effective strategy for expanding the donor pool and ensuring favorable graft outcomes.


Assuntos
Transplante de Rim , Adulto , Criança , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Sobrevivência de Enxerto , Doadores de Tecidos , Rim
14.
Healthcare (Basel) ; 12(6)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38540604

RESUMO

BACKGROUND: Identifying the potential factors of depression among medical students is the first step towards academic excellence and future safe medical practice. METHODS: A cross-sectional study was conducted from December 2019 to February 2020 at the University of Bisha, College of Medicine (UBCOM), Bisha Province, Saudi Arabia. Male medical students from year one to year six were involved. A self-administered questionnaire was used to collect data about students' socio-demographic and academic characteristics. The Arabic version of the PHQ-9 scale with a score of ≥10 was used to identify depression. Logistic regression analysis was used to assess the prevalence and correlates of depression. RESULTS: Of the 190 male students enrolled, 26.8% had depressive symptoms, of whom 45.1% were experiencing moderate to severe symptoms. The significantly highest depression rate was found among the second-year students, at 43.8% (OR = 2.544; 95% CI 1.178-5.714; p = 0.018), and the lowest rate was found among year one students, at 8.9% (OR = 0.203; 95% CI 0.075-0.560; p = 0.002). Univariate regression revealed a significant correlation between depression and dissatisfaction with family income, loss of family members, having psychological illness, difficulties in personal relationships, regretting studying medicine, failure in an academic year, a lower grade than expected, conflict with tutors, lack of college facilities and heavy academic load. In multivariate analysis, loss of family members (AOR = 3.69; 95% CI 1.86-7.413), difficulties in personal relationships (AOR = 2.371; 95% CI 1.009-5.575), regretting studying medicine (AOR = 3.764; 95% CI 1.657-8.550), and failing an academic year (AOR = 2.559; 95% CI 1.112-5.887) were independently correlated with depression. CONCLUSIONS: The study concluded that medical students at UBCOM experience depressive symptoms associated with various risk indicators. Optimizing the educational and social environment and infrastructure facilities at UBCOM might promote students' mental health and well-being.

15.
Cancer Metastasis Rev ; 43(1): 293-319, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38438800

RESUMO

Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic and normoxic conditions and is a well-studied reprogramming of metabolism in cancer. Interestingly, the alteration of other metabolic pathways, especially lipid metabolism has also grabbed the attention of scientists worldwide. Lipids, primarily consisting of fatty acids, phospholipids and cholesterol, play essential roles as structural component of cell membrane, signalling molecule and energy reserves. This reprogramming primarily involves aberrations in the uptake, synthesis and breakdown of lipids, thereby contributing to the survival, proliferation, invasion, migration and metastasis of cancer cells. The development of resistance to the existing treatment modalities poses a major challenge in the field of cancer therapy. Also, the plasticity of tumor cells was reported to be a contributing factor for the development of resistance. A number of studies implicated that dysregulated lipid metabolism contributes to tumor cell plasticity and associated drug resistance. Therefore, it is important to understand the intricate reprogramming of lipid metabolism in cancer cells. In this review, we mainly focused on the implication of disturbed lipid metabolic events on inducing tumor cell plasticity-mediated drug resistance. In addition, we also discussed the concept of lipid peroxidation and its crucial role in phenotypic switching and resistance to ferroptosis in cancer cells. Elucidating the relationship between lipid metabolism, tumor cell plasticity and emergence of resistance will open new opportunities to develop innovative strategies and combinatorial approaches for the treatment of cancer.


Assuntos
Metabolismo dos Lipídeos , Neoplasias , Humanos , Plasticidade Celular , Neoplasias/patologia , Resistencia a Medicamentos Antineoplásicos , Colesterol/metabolismo
16.
Cancer Metastasis Rev ; 43(1): 321-362, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517618

RESUMO

Recent advances have brought forth the complex interplay between tumor cell plasticity and its consequential impact on drug resistance and tumor recurrence, both of which are critical determinants of neoplastic progression and therapeutic efficacy. Various forms of tumor cell plasticity, instrumental in facilitating neoplastic cells to develop drug resistance, include epithelial-mesenchymal transition (EMT) alternatively termed epithelial-mesenchymal plasticity, the acquisition of cancer stem cell (CSC) attributes, and transdifferentiation into diverse cell lineages. Nuclear receptors (NRs) are a superfamily of transcription factors (TFs) that play an essential role in regulating a multitude of cellular processes, including cell proliferation, differentiation, and apoptosis. NRs have been implicated to play a critical role in modulating gene expression associated with tumor cell plasticity and drug resistance. This review aims to provide a comprehensive overview of the current understanding of how NRs regulate these key aspects of cancer biology. We discuss the diverse mechanisms through which NRs influence tumor cell plasticity, including EMT, stemness, and metastasis. Further, we explore the intricate relationship between NRs and drug resistance, highlighting the impact of NR signaling on chemotherapy, radiotherapy and targeted therapies. We also discuss the emerging therapeutic strategies targeting NRs to overcome tumor cell plasticity and drug resistance. This review also provides valuable insights into the current clinical trials that involve agonists or antagonists of NRs modulating various aspects of tumor cell plasticity, thereby delineating the potential of NRs as therapeutic targets for improved cancer treatment outcomes.


Assuntos
Plasticidade Celular , Neoplasias , Humanos , Plasticidade Celular/fisiologia , Neoplasias/patologia , Transdução de Sinais , Transição Epitelial-Mesenquimal/fisiologia , Resistencia a Medicamentos Antineoplásicos , Receptores Citoplasmáticos e Nucleares/metabolismo , Células-Tronco Neoplásicas/patologia
17.
Front Public Health ; 12: 1348370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515594

RESUMO

Background: Tobacco smoking is one of the most significant health-related problems worldwide. However, the prevalence and sociodemographic determinants of tobacco and nicotine use among students on healthcare courses in Saudi Arabia are limited. Methods: This cross-sectional study used a questionnaire that was distributed via SurveyMonkey between November 2022 and June 2023 to all student universities offering healthcare courses. Data are presented as frequency and percentages. The associated sociodemographic factors with current tobacco and nicotine use were subjected to logistic regression. Results: Overall, 5,012, of whom 3,872 (77.25%) were males, responded to the online survey. The prevalence of current tobacco and nicotine use was 3,553 (71%). The majority of users used electronic nicotine delivery systems (1,622: 32.36%). The current use of cigarettes (AOR: 1.75 (1.42 to 2.15)), e-cigarettes (AOR: 1.17 (1.01 to 1.37)), and smokeless tobacco substances (AOR: 1.35 (1.02 to 1.90)) were more pronounced among males compared to female students. However, the current use of a hookah was less among males (AOR: 0.74 (95% CI: 61 to 0.91)). Smoking cigarettes was practiced less among students living in other regions compared to the Central Region. However, smokeless tobacco substances seem to be more prevalent in the Western, Southern, and Northern Regions, (AOR: 1.57 (95% CI: 1.09 to 2.26)), (AOR: 1.43 (95% CI: 1.04 to 1.95)), and (AOR: 1.57 (95% CI: 1.09 to 2.26)), respectively. Conclusion: Smoking is prevalent among students in the healthcare disciplines, with electronic nicotine delivery systems being the most used product. Several sociodemographic factors were associated with higher tobacco or nicotine use.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Uso de Tabaco , Feminino , Humanos , Masculino , Estudos Transversais , Atenção à Saúde , Prevalência , Arábia Saudita/epidemiologia , Estudantes , Universidades
18.
Arch Biochem Biophys ; 754: 109958, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499054

RESUMO

The aryl hydrocarbon receptor (AhR) functions as a vital ligand-activated transcription factor, governing both physiological and pathophysiological processes. Notably, it responds to xenobiotics, leading to a diverse array of outcomes. In the context of drug repurposing, we present here a combined approach of utilizing structure-based virtual screening and molecular dynamics simulations. This approach aims to identify potential AhR modulators from Drugbank repository of clinically approved drugs. By focusing on the AhR PAS-B binding pocket, our screening protocol included binding affinities calculations, complex stability, and interactions within the binding site as a filtering method. Comprehensive evaluations of all DrugBank small molecule database revealed ten promising hits. This included flibanserin, butoconazole, luliconazole, naftifine, triclabendazole, rosiglitazone, empagliflozin, benperidol, nebivolol, and zucapsaicin. Each exhibiting diverse binding behaviors and remarkably very low binding free energy. Experimental studies further illuminated their modulation of AhR signaling, and showing that they are consistently reducing AhR activity, except for luliconazole, which intriguingly enhances the AhR activity. This work demonstrates the possibility of using computational modelling as a quick screening tool to predict new AhR modulators from extensive drug libraries. Importantly, these findings hold immense therapeutic potential for addressing AhR-associated disorders. Consequently, it offers compelling prospects for innovative interventions through drug repurposing.


Assuntos
Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/metabolismo , Sítios de Ligação , Ligação Proteica , Domínios Proteicos , Ligantes
20.
Int J Gen Med ; 17: 1007-1015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505144

RESUMO

Background: Nearly half of the Systemic lupus erythematosus (SLE) patients develop lung involvement. The study assessed the extent of pulmonary involvement among SLE patients and to identify the associated factors in the population. Methodology: This retrospective cohort study was conducted at Aseer Hospital and Khamis Myshat Hospital in the Southern region of Saudi Arabia. The study spanned from January 1, 2016, to June 3, 2023. Patient inclusion criteria encompassed individuals who received a definitive diagnosis and classification as per American College of Rheumatology criteria, while patients under 18 years of age and those with mixed connective tissue diseases were exclude. Results: A total of 247 participants were included. 41.7% (n=103) aged 41 years and older, 95.1% (n = 235) were females. Around 10.10% had diabetes mellitus and 17.00% had hypertension and hypothyroidism. Lupus Nephritis was in 15.40%. Chest involvement was reported in 21.9%, in the form of pleuritis (6.10%), pleural effusion (4.00%), and lupus pneumonitis (4.00%), interstitial lung disease (4.00%), pulmonary embolism (3.60%) of individuals, and pulmonary hemorrhage (2.80%). The respiratory symptoms reported by SLE were; dyspnea, cough, and chest pain each having a prevalence of around 18.0%. Palpitations have a relatively high occurrence at 13.80%. Meanwhile, hemoptysis (blood coughing) has a lower prevalence of 1.20%, and fever is reported at 2.80%. Having chronic kidney disease and hypertension were significantly associated with having pulmonary involvement; (χ2=3.308, p=0.027) and (χ2=7.782, Fisher's p=0.002) respectively. The seropositivity for antiphospholipid Abs, anti-CCP, and antids-DNA were significantly associated with pulmonary involvement (χ2=3.239, =p=0.049), (χ2=4.621, Fisher's p=0.023), and (χ2=8.248, p=0.010) respectively. Conclusion: The study found that 21.9% of SLE patients experience chest involvement, with varying degrees of pulmonary symptoms. Factors such as chronic kidney disease, hypertension, antiphospholipid antibodies, Anti-CCP positivity, and seropositivity for Anti-dsDNA were found to be significant associations with lung involvement, contributing to our understanding of SLE.

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