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1.
Cancer Med ; 13(9): e7193, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738459

RESUMO

BACKGROUND: Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single-center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly-diagnosed PCNSL. METHODS: Sixty-nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment. RESULTS: After a median follow-up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression-free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life. CONCLUSIONS: The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.


Assuntos
Neoplasias do Sistema Nervoso Central , Lenalidomida , Quimioterapia de Manutenção , Metotrexato , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Idoso , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Adulto , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Intervalo Livre de Progressão , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
2.
Front Immunol ; 15: 1394925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690282

RESUMO

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.


Assuntos
Metabolismo Energético , Estresse Oxidativo , Sepse , Sirtuínas , Humanos , Sepse/tratamento farmacológico , Sepse/imunologia , Sepse/metabolismo , Animais , Sirtuínas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/imunologia
3.
Sci Rep ; 14(1): 6200, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486026

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Aminoácidos/metabolismo , Glicólise , Lipídeos
4.
J Exp Bot ; 75(10): 3188-3200, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38401150

RESUMO

The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition in Arabidopsis depends considerably on excessive iron deposition in the root apoplast. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR) and LPR2 attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ferro , Raízes de Plantas , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Ferro/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Concentração de Íons de Hidrogênio , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Espécies Reativas de Oxigênio/metabolismo
5.
Discov Oncol ; 15(1): 33, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38341827

RESUMO

Malignant tumours of the digestive system cover a wide range of diseases that affect the health of people to a large extent. Angiogenesis is indispensable in the development, and metastasis of tumours, mainly in two ways: occupation or formation. Vessels can provide nutrients, oxygen, and growth factors for tumours to encourage growth and metastasis, so cancer progression depends on simultaneous angiogenesis. Recently, exosomes have been proven to participate in the angiogenesis of tumours. They influence angiogenesis by binding to tyrosine kinase receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 with different affinities, regulating Yap-VEGF pathway, Akt pathway or other signaling pathway. Additionally, exosomes are potential therapeutic vectors that can deliver many types of cargoes to different cells. In this review, we summarize the roles of exosomes in the angiogenesis of digestive system tumours and highlight the clinical application prospects, directly used as targers or delivery vehicles, in antiangiogenic therapy.

7.
MedComm (2020) ; 5(2): e472, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38292328

RESUMO

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

8.
Exp Dermatol ; 33(1): e15012, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284204

RESUMO

Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.


Assuntos
Dermatite Atópica , Eczema , Terapia Ultravioleta , Humanos , Dermatite Atópica/radioterapia , Estudos Prospectivos , Método Duplo-Cego , Qualidade de Vida , Terapia Ultravioleta/efeitos adversos , Fototerapia , Prurido/etiologia , Prurido/radioterapia , Resultado do Tratamento
9.
J Mol Graph Model ; 127: 108669, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38011826

RESUMO

Fragment-based drug design (FBDD) is one major drug discovery method employed in computer-aided drug discovery. Due to its inherent limitations, this process experiences long processing times and limited success rates. Here we present a new Fragment Databases from Screened Ligands Drug Design method (FDSL-DD) that intelligently incorporates information about fragment characteristics into a fragment-based design approach to the drug development process. The initial step of the FDSL-DD is the creation of a fragment database from a library of docked, drug-like ligands for a specific target, which deviates from the traditional in silico FBDD strategy, incorporating structure-based design screening techniques to combine the advantages of both approaches. Three different protein targets have been tested in this study to demonstrate the potential of the created fragment library and FDSL-DD. Utilizing the FDSL-DD led to an increase in binding affinity for each protein target. The most substantial increase was exhibited by the ligand designed for TIPE2, with a 3.6 kcalmol-1 difference between the top ligand from the FDSL-DD and top ligand from the high throughput virtual screening (HTVS). Using drug-like ligands in the initial HTVS allows for a greater search of chemical space, with higher efficiency in fragments selection, less grid boxes, and potentially identifying more interactions.


Assuntos
Desenho de Fármacos , Descoberta de Drogas , Ligantes , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala , Bases de Dados Factuais
10.
Intern Emerg Med ; 19(2): 321-332, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37999870

RESUMO

Stopping smoking is crucial for public health and especially for individuals with diabetes. Combustion-free nicotine alternatives like e-cigarettes and heated tobacco products are increasingly being used as substitutes for conventional cigarettes, contributing to the decline in smoking prevalence. However, there is limited information about the long-term health impact of those products in patients with diabetes. This randomized controlled trial aims to investigate whether switching from conventional cigarettes to combustion-free nicotine alternatives will lead to a measurable improvement in cardiovascular risk factors and metabolic parameters over a period of 2 years in smokers with type 2 diabetes. The multicenter study will be conducted in seven sites across four countries. A total of 576 smokers with type 2 diabetes will be randomly assigned (1:2 ratio) to either standard of care with brief cessation advice (Control Arm) or combustion-free nicotine alternatives use (Intervention Arm). The primary end point is the change in the proportion of patients with metabolic syndrome between baseline and the 2-year follow-up. Additionally, the study will analyze the absolute change in the sum of the individual factors of metabolic syndrome at each study time point. Patient recruitment has started in September 2021 and enrollment is expected to be completed by December 2023. Results will be reported in 2026. This study may provide valuable insights into cardiovascular and metabolic health benefits or risks associated with using combustion-free nicotine alternatives for individuals with type 2 diabetes who are seeking alternatives to tobacco cigarette smoking. The study protocol, informed consent forms, and relevant documents were approved by seven ethical review boards. Study results will be disseminated through articles published in high-quality, peer-reviewed journals and presentations at conferences.


Assuntos
Doenças Cardiovasculares , Fumar Cigarros , Diabetes Mellitus Tipo 2 , Sistemas Eletrônicos de Liberação de Nicotina , Síndrome Metabólica , Abandono do Hábito de Fumar , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco de Doenças Cardíacas , Estudos Multicêntricos como Assunto , Nicotina , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(12): 1211-1218, 2023 Dec 15.
Artigo em Chinês | MEDLINE | ID: mdl-38112137

RESUMO

OBJECTIVES: Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). METHODS: Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD. RESULTS: The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD. CONCLUSIONS: Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.


Assuntos
Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Lactente , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Contagem de Linfócitos , Subpopulações de Linfócitos , Estudos Retrospectivos
12.
Nat Commun ; 14(1): 7676, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-37996415

RESUMO

Engineering an efficient semiconductor to sustainably produce green hydrogen via solar-driven water splitting is one of the cutting-edge strategies for carbon-neutral energy ecosystem. Herein, a superhydrophilic green hollow ZnIn2S4 (gZIS) was fabricated to realize unassisted photocatalytic overall water splitting. The hollow hierarchical framework benefits exposure of intrinsically active facets and activates inert basal planes. The superhydrophilic nature of gZIS promotes intense surface water molecule interactions. The presence of vacancies within gZIS facilitates photon energy utilization and charge transfer. Systematic theoretical computations signify the defect-induced charge redistribution of gZIS enhancing water activation and reducing surface kinetic barriers. Ultimately, the gZIS could drive photocatalytic pure water splitting by retaining close-to-unity stability for a full daytime reaction with performance comparable to other complex sulfide-based materials. This work reports a self-activated, single-component cocatalyst-free gZIS with great exploration value, potentially providing a state-of-the-art design and innovative aperture for efficient solar-driven hydrogen production to achieve carbon-neutrality.

13.
Food Res Int ; 173(Pt 2): 113452, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803777

RESUMO

Seeds of the species Acacia retinodes, A. provincialis, and A. tenuissima) from different growing locations were analysed for their mineral composition, free and bound polyphenols, and flavonoids. Previous research has studied these compounds in only a limited number of Acacia species, and only one study reports significant differences between three species. All species were rich in potassium (353 - 427 mg/100 g), sodium (14 - 240 mg/100 g) and iron (7 - 8 mg/100 g). The free polyphenol extracts of all species had higher total phenolic content, total flavonoid content and antioxidant activities than their bound counterparts, indicating the possibility of higher bioavailability than the bound polyphenol extracts. The predominant phenolic compounds found in the Acacia polyphenol seed extracts were 6-Hydroxy-2-methylindole and 2,2'-Methylenebis(6-tert-butyl-methylphenol), though no phenolic compounds were identified in the bound extracts of A. retinodes Grampians and A. provincialis Tarrington. Other compounds identified in the seed extracts include sucrose, d-fructofuranose and d-pinitol.


Assuntos
Acacia , Antioxidantes , Antioxidantes/análise , Extratos Vegetais/análise , Fenóis/análise , Polifenóis/análise , Flavonoides/análise , Sementes/química , Minerais
15.
Front Med (Lausanne) ; 10: 1253839, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37746085

RESUMO

Background: Gout is associated with significant morbidity and mortality, yet suboptimal gout control remains a problem globally. Identifying the risk factors associated with poor gout control among patients in primary care allows targeted interventions to improve their clinical management. This study aimed to determine the prevalence of poor gout control and its associated demographic and clinical factors among urbanized community-dwelling Asian patients. Methods: This retrospective study was based on data extracted from the electronic medical records of 8 public primary care clinics in Singapore. Patients with a diagnostic code of gout who had 2 or more visits between 1st January 2018 and 31st December 2019 were included in the analysis. Data extracted included: demographics, anthropological measurements, comorbidities, serum uric acid levels and medication prescription. A patient is defined to have poor gout control if they suffer two or more acute gout attacks within a year. Chi-Squared test was used for categorical parameters. For continuous variables, univariate logistic regression analysis was first performed. Significant factors (p ≤ 0.1) were then included in the logistics regression model to account for confounders. Results: A total of 7,970 patients and 24,624 visits were included in the analysis. The prevalence of poorly controlled gout was 28.2% (n = 2,244/7,970); only 46.3% of them (n = 1,039/2,244) were prescribed allopurinol and 13.4% (n = 301/2,244) were taking doses ≥300 mg. Using logistic regression, factors associated with poor gout control were: male gender [adjusted OR (AOR) =1.66, p < 0.001], Malay ethnicity (AOR = 1.27, p = 0.007), congestive heart failure (AOR = 1.64, p = 0.037). Patients prescribed allopurinol (AOR = 1.52, p < 0.001), NSAIDs (AOR = 2.76, p < 0.001) and corticosteroids (AOR = 2.83, p < 0.001) were more likely to have poorly-controlled gout. Conclusion: Nearly 30% of patients had poor gout. Interventions should focus on male and Malay patients and those with congestive cardiac failure.

16.
Explor Res Clin Soc Pharm ; 11: 100325, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37694168

RESUMO

Background: Effective communication that integrates the value of patient-centered care is important in healthcare encounters. Communication skills training (CST) has been indicated as effective in improving patient-centered communication behaviors. However, there is a paucity of studies on the impact of CST among Malaysian hospital pharmacists. Objective: This study aimed to evaluate the effects of a patient-centered CST program on patient-centered communication scores, communication self-efficacy, and attitudes toward concordance among pharmacists in public hospitals. Methods: A communication skills training (CST) program was conducted among hospital pharmacists. This training intervention was developed based on patient-centered communication frameworks and techniques, namely the Four Habits Model and motivational interviewing. A pre-test/post-test quasi-experimental design was implemented for the evaluation. Pharmacists underwent pre-test/post-test audiotaped simulated consultations and completed questionnaires, including the Revised United States-Leeds Attitudes Toward Concordance scale (RUS-LATCon) and Communication Self-Efficacy scale. The Four Habits Coding Scheme (FHCS) was used to evaluate patient-centered communication scores from the audiotapes, and the Wilcoxon signed-rank test was used to analyze for differences in the pre- and post-intervention scores. Results: A total of 38 pharmacists from four tertiary hospitals participated in this study and completed the pre-test. However, due to the impact of COVID-19, only 23 pharmacists completed the post-test data collection. Improvements were noted in the FHCS scores post-training, including items related to exploring patients' concerns, acceptability, and barriers to treatment. Based on the questionnaire, there was an improvement in recognizing patients' needs and potential medication uncertainty and an increase in the overall communication self-efficacy scores after the training. Conclusions: CST may help improve the adoption of patient-centered communication in pharmacists' consultations with patients.

17.
PLoS One ; 18(9): e0290883, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37768930

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death and disability worldwide, imposing a significant burden on patients and healthcare systems. The role of pharmacists in reducing cardiovascular disease (CVD) is pivotal as they play an essential part in the healthcare team, particularly in medication management and patient education. Pharmacists are well-positioned to contribute to the prevention and control of CVD through various roles, including medication management and patient education. This study aims to investigate the current involvement of community pharmacists in Malaysia, specifically in cardiovascular diseases-related health promotion activities and dyslipidemia management, including their perceived barriers. METHOD: This cross-sectional survey was conducted among community pharmacists in all 14 states of Malaysia between November 2021 and July 2022. The self-administered survey was shared to relevant groups through various social media platforms. RESULTS: A total of 312 community pharmacists were involved in the survey. Majority of the respondents were females (66%), with a mean age (SD) of 32.9 (8.4) years. Most of the respondents showed satisfactory practice for patient counselling, but improvements are needed particularly in risk assessment and collaborative care aspect. Most of them expressed their interest for dyslipidemia management training (89.4%). Lack of access to medical records (71.2%) and lack of CVD-related educational materials (70.8%) were the two main perceived barriers identified. CONCLUSION: Community pharmacists in Malaysia provide a satisfactory role in the provision of cardiovascular disease-related health promotion activities, especially in providing patient counselling. Strengthening collaborative care is essential for providing comprehensive and patient-centered intervention in dyslipidemia management. This requires ongoing efforts to address and overcome existing barriers for effective teamwork and coordination among healthcare professionals.


Assuntos
Doenças Cardiovasculares , Serviços Comunitários de Farmácia , Dislipidemias , Feminino , Humanos , Adulto , Masculino , Estudos Transversais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Farmacêuticos , Malásia , Papel Profissional , Promoção da Saúde/métodos , Dislipidemias/tratamento farmacológico
18.
J Microbiol Immunol Infect ; 56(6): 1169-1177, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37709632

RESUMO

BACKGROUND: Outbreak of Omicron BA.2 in Taiwan led to an increased number of acute encephalitis/encephalopathy cases in children and several fatal cases drew public attention. In pre-Omicron period, pediatric cases of COVID-19-associated acute encephalitis have been reported and during Omicron epidemic, febrile convulsions, encephalitis were mentioned more frequently. The outcome of patients with neurological complications was worse. However, few studies investigated the risk factors, pathophysiology and prognosis of COVID-19-associated encephalitis/encephalopathy. Here, we describe the presentation of pediatric cases of COVID-19-associated acute encephalitis/encephalopathy and explore the associated risk factors. METHODS: Pediatric patients with confirmed SARS-CoV-2 infections were prospectively enrolled at admission at Chang Gung Memorial Hospital between April and August 2022. Patients were categorized into groups of acute encephalitis/encephalopathy, febrile convulsions or mild disease. Demographic descriptions, clinical manifestations and laboratory data were collected. RESULTS: Of 288 acute COVID-19 patients, there were 38 (13.2%) acute encephalitis/encephalopathy, 40 (13.9%) febrile convulsions, and 210 (72.9%) mild disease. Among acute encephalitis/encephalopathy group, the mean age was 68.3 ± 45.0 months. The common neurological symptoms were lethargy (65.8%), seizures (52.6%), and impaired consciousness (34.2%). Over 3 years old (adjusted odds ratio [aOR]: 7.57, p < 0.001), absolute neutrophil count ≥3150/µL (aOR: 5.46, p = 0.008), and procalcitonin ≥0.5 ng/mL (aOR: 4.32, p = 0.021) were independent factors for acute encephalitis/encephalopathy. CONCLUSIONS: Most cases of COVID-19-associated acute encephalitis/encephalopathy showed no evidence of direct viral invasion but associations with older age, increased peripheral neutrophil, and serum procalcitonin. These findings may imply the neutrophil-mediated systemic inflammatory response plays an important role on central nerve system, leading to cerebral dysfunction.


Assuntos
Encefalopatias , COVID-19 , Encefalite , Convulsões Febris , Criança , Humanos , Lactente , Pré-Escolar , Convulsões Febris/epidemiologia , Convulsões Febris/complicações , Pró-Calcitonina , Encefalopatias/epidemiologia , Encefalopatias/complicações , Encefalite/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , Fatores de Risco
19.
Front Pharmacol ; 14: 1260697, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711170

RESUMO

Background: Colorectal cancer (CRC) is one of the most prevalent cancer types globally. A survival paradox exists due to the inherent heterogeneity in stage II/III CRC tumor biology. Ferroptosis is closely related to the progression of tumors, and ferroptosis-related genes can be used as a novel biomarker in predicting cancer prognosis. Methods: Ferroptosis-related genes were retrieved from the FerrDb and KEGG databases. A total of 1,397 samples were enrolled in our study from nine independent datasets, four of which were integrated as the training dataset to train and construct the model, and validated in the remaining datasets. We developed a machine learning framework with 83 combinations of 10 algorithms based on 10-fold cross-validation (CV) or bootstrap resampling algorithm to identify the most robust and stable model. C-indice and ROC analysis were performed to gauge its predictive accuracy and discrimination capabilities. Survival analysis was conducted followed by univariate and multivariate Cox regression analyses to evaluate the performance of identified signature. Results: The ferroptosis-related gene (FRG) signature was identified by the combination of Lasso and plsRcox and composed of 23 genes. The FRG signature presented better performance than common clinicopathological features (e.g., age and stage), molecular characteristics (e.g., BRAF mutation and microsatellite instability) and several published signatures in predicting the prognosis of the CRC. The signature was further stratified into a high-risk group and low-risk subgroup, where a high FRG signature indicated poor prognosis among all collected datasets. Sensitivity analysis showed the FRG signature remained a significant prognostic factor. Finally, we have developed a nomogram and a decision tree to enhance prognosis evaluation. Conclusion: The FRG signature enabled the accurate selection of high-risk stage II/III CRC population and helped optimize precision treatment to improve their clinical outcomes.

20.
Am J Cancer Res ; 13(7): 2886-2905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560001

RESUMO

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. LRP1B was initially identified as a cancer suppressor in several cancers. However, the potential biological phenotypes and molecular mechanisms of LRP1B in LUAD have not been fully investigated. In our study, we showed that the expression of LRP1B in LUAD tissues was lower than that in normal tissues. Knockdown of LRP1B markedly enhanced malignancy of LUAD cells. Genomic analysis indicated that the population expressing low-levels of LRP1B had higher genomic instability, which accounted for a larger proportion of aneuploidy and inflammation subtyping. Enrichment analysis of bulk and cell-line transcriptomic data both showed that the low expression of LRP1B could induce the activation of IL-6-JAK-STAT3, chemokine, cytokine, and other inflammation signaling pathways. Moreover, our findings revealed that knockdown LRP1B enhanced the secretion of IL-6 and IL-8, as confirmed by ELISA assays. Further validation using PCR and WB confirmed that downregulation of LRP1B mRNA significantly upregulated the activity of the IL-6-JAK-STAT3 pathway. Collectively, this study highlights LRP1B as a tumor suppressor gene and reveals that LRP1B knockdown promotes malignant progression in LUAD by inducing inflammation through the IL-6-JAK-STAT3 pathway.

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