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Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012-2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin's link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23-3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05-1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17-2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67-11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.
This pioneering study identified potential independent risk factors and the cycle-to-shock of oxaliplatin-associated shock which is a rare but life-threatening adverse event Why was the study done? Oxaliplatin-induced anaphylactic shock (referred to as shock) is a rare but life-threatening adverse event which is a harmful and undesirable experience associated with medical care in a patient. What did the researchers do? This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock and assess the cycle-to-shock during oxaliplatin treatment. All newly diagnosed stage III CRC patients were identified from the CRC Health Database (20122016). The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Conditional logistic regression was used to quantify the association between oxaliplatin and shock incidence. What did the researchers find? Among 6,932 oxaliplatin recipients, 331 suffered shock. 3,309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock. Independent risk factors were male sex and heart diseases. The risk of shock was 33% higher for males and 65% higher for people with heart diseases compared to females and those without heart diseases. The case-crossover analysis revealed a more than four-fold risk of shock of oxaliplatin. Twenty-two of 331 shock cases were exposed to oxaliplatin within two days before the shock onset. The median cycle-to-shock time is at the seventh cycle. What do the findings mean? Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and having heart diseases are two independent risk factors.
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Introduction: Schizophrenia increases the risk of mortality and cardiovascular disease (CVD) risk. However, the correlation between antipsychotics (APs) and CVD remains controversial. Hyperlipidemia is a significant risk factor for CVD. Methods: We conducted a nationwide population-based retrospective cohort study to investigate the effects of APs on the risk of hyperlipidemia and lipid homeostasis gene expression. We used data from the Longitudinal Health Insurance Database of Taiwan on new-onset schizophrenia patients and a comparison cohort without schizophrenia. We used a Cox proportional hazards regression model to analyze the differences in hyperlipidemia development between the two cohorts. Furthermore, we examined the effects of APs on the hepatic expression of lipid homeostasis-related genes. Results: After adjusting for potential interrelated confounding factors, the case group (N = 4,533) was found to have a higher hyperlipidemia risk than the control cohort (N = 4,533) [adjusted hazard ratio (aHR), 1.30, p < 0.001]. Patients with schizophrenia without APs had a significantly higher risk of hyperlipidemia (aHR, 2.16; p < 0.001). However, patients receiving APs had a significantly lower risk of hyperlipidemia than patients not receiving APs (all aHR ≤ 0.42, p < 0.001). First-generation antipsychotics (FGAs) induce the expression of hepatic lipid catabolism genes in an in vitro model. Discussion: Patients with schizophrenia had a higher risk of hyperlipidemia than controls; however, compared with non-treated patients, AP users had a lower risk of hyperlipidemia. Early diagnosis and management of hyperlipidemia may help prevent CVD.
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Polymethoxyflavones (PMFs) in citrus fruits have a variety of biological activities, including antioxidant, anti-inflammatory, anticancer, and anti-atherosclerotic effects. The liver is the major detoxifying organ of the human body; however, factors such as acetaminophen (APAP) overdose may increase oxidative stress in liver cells and lead to severe liver failure. In this study we examined the effects of tangeretin (TAN), a common citrus PMF, and its metabolite 4'-demethyltangeretin (4'-OH-TAN) on activation of the Nrf2 antioxidant system in mouse AML-12 hepatocytes through regulation by epigenetic mechanisms. The ability of TAN and 4'-OH-TAN to inhibit APAP-induced hepatotoxicity was also evaluated. The results showed that TAN and 4'-OH-TAN significantly increased the mRNA and protein levels of Nrf2 and Nrf2-mediated antioxidant and detoxifying enzymes (UGT1A, HO-1, and NQO1) in AML-12 cells. TAN and 4'-OH-TAN also suppressed protein expression of histone deacetylases (HDACs) and DNA methyltransferases (DMNTs) and reduced DNA methylation of the nrf2 promoter. Furthermore, TAN and 4'-OH-TAN prevented APAP-induced injury and inhibited APAP-induced ROS generation in AML-12 cells. Based on these results, we conclude that TAN and 4'-OH-TAN may increase the antioxidant capacity of liver cells by regulating epigenetic alteration to activate the Nrf2-related antioxidant system, thereby preventing liver cells from being damaged by APAP-induced oxidative stress.
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Doença Hepática Induzida por Substâncias e Drogas , Leucemia Mieloide Aguda , Animais , Camundongos , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Acetaminofen/metabolismo , Estresse Oxidativo , Fígado/metabolismo , Hepatócitos , Epigênese Genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Introduction: A potential association between epilepsy and subsequent type 2 diabetes mellitus (T2DM) has emerged in recent studies. However, the association between epilepsy, anti-epileptic drugs (AEDs), and the risk of T2DM development remains controversial. We aimed to conduct a nationwide, population-based, retrospective, cohort study to evaluate this relationship. Methods: We extracted data from the Taiwan Longitudinal Generation Tracking Database of patients with new-onset epilepsy and compared it with that of a comparison cohort of patients without epilepsy. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing T2DM between the two cohorts. Next-generation RNA sequencing was used to characterize T2DM-related molecularchanges induced by AEDs and the T2DM-associated pathways they alter. The potential of AEDs to induce peroxisome proliferator-activated receptor γ (PPARγ) transactivation was also evaluated. Results: After adjusting for comorbidities and confounding factors, the case group (N = 14,089) had a higher risk for T2DM than the control group (N = 14,089) [adjusted hazards ratio (aHR), 1.27]. Patients with epilepsy not treated with AEDs exhibited a significantly higher risk of T2DM (aHR, 1.70) than non-epileptic controls. In those treated with AEDs, the risk of developing T2DM was significantly lower than in those not treated (all aHR ≤ 0.60). However, an increase in the defined daily dose of phenytoin (PHE), but not of valproate (VPA), increased the risk of T2DM development (aHR, 2.28). Functional enrichment analysis of differentially expressed genes showed that compared to PHE, VPA induced multiple beneficial genes associated with glucose homeostasis. Among AEDs, VPA induced the specific transactivation of PPARγ. Discussion: Our study shows epilepsy increases the risk of T2DM development, however, some AEDs such as VPA might yield a protective effect against it. Thus, screening blood glucose levels in patients with epilepsy is required to explore the specific role and impact of AEDs in the development of T2DM. Future in depth research on the possibility to repurpose VPA for the treatment of T2DM, will offer valuable insight regarding the relationship between epilepsy and T2DM.
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Diabetes Mellitus Tipo 2 , Epilepsia , Humanos , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , PPAR gama/genética , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Ativação Transcricional , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologiaRESUMO
Background: Clinical trials investigating the effects of beta-blockers (BBs) on cancer are underway. Evidence from preclinical research suggests that BBs could serve as anticancer agents and immune boosters. There is conflicting evidence regarding the effect of BB use on clinical outcomes in patients with breast cancer. Objectives: The study aimed to determine whether BB use is associated with progression-free survival (PFS) and overall survival (OS) in patients receiving anti-human epidermal growth factor receptor 2 (HER2) treatment for advanced breast cancer. Design: Retrospective hospital-based study. Methods: The participants enrolled were breast cancer patients with advanced HER2-positive status who initiated trastuzumab monotherapy or concomitant therapy with trastuzumab and any dose of BB. The patients were enrolled between January 2012 and May 2021 and divided into three groups based on whether they received a BB or not in the therapeutic regimen: BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+. PFS and OS were the primary and secondary endpoints, respectively. Results: The estimated median PFS in the BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+ groups was 51.93, 21.50, and 20.77 months, respectively. The corresponding OS was 56.70, 29.10, and 27.17 months. The intergroup differences in these durations were significant. Both PFS [adjusted hazard ratio (HR): 2.21, 95% confidence interval (CI): 1.56-3.12; p < 0.001]) and OS (adjusted HR: 2.46, 95% CI: 1.69-3.57; p < 0.001) were worse when BBs were used. Conclusion: Our study provides important evidence that BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. Nevertheless, despite the study's results, cardiovascular disease (CVD) should be appropriately treated in patients with HER2-positive advanced breast cancer. Other types of drugs can be used to treat CVD, but BB use should be avoided. Large real-world database and prospective studies should be conducted to validate the results of this study.
Use of beta-blockers for cancer therapy Summary: Background ⢠Evidence from preclinical research suggests that beta-blockers (BBs) could serve as anticancer agents and immune boosters. ⢠Beta-blockers could therefore be a potential therapy for cancers. ⢠Trastuzumab is a drug that affects the overall survival (OS) and progression-free survival (PFS) of patients with HER2-positive breast cancer by binding to the extracellular domain of HER2. ⢠This study investigates the effect of BBs on trastuzumab therapy in patients with advanced breast cancer. Method ⢠This retrospective study was conducted between January 2012 and May 2021. ⢠Patients with HER2-positive advanced breast cancer who were treated using trastuzumab monotherapy or trastuzumab concomitantly with any dose of a BB were recruited and divided into three groups. ⢠One group received only the trastuzumab (BB−/trastuzumab+), another group received both BB+ (non-selective) and trastuzumab [BB+ (non-selective)/trastuzumab+], and the third group received both BB+ (selective) and trastuzumab [BB+ (selective)/trastuzumab+]. ⢠The PFS and OS were determined and compared between the treatment groups. Results ⢠We enrolled 221 patients (mean age: 56.1 ± 11.1 years) in the study. ⢠The estimated median PFS and OS were significantly lower in the BB+ (non-selective)/trastuzumab+ and BB+ (selective)/trastuzumab+ groups than in the BB−/trastuzumab+ group. ⢠The use of BBs was associated with worse PFS and OS in patients with HER2-positive advanced breast cancer. Conclusion ⢠Trastuzumab treatment was independently associated with poorer PFS and OS for patients who used BB prior to initiating trastuzumab therapy for advanced HER2-positive breast cancer. ⢠BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. ⢠Future studies with larger sample sizes are needed to validate our findings.
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BACKGROUND: Non-cancer drugs are currently being repurposed for cancer treatment. Mounting evidence highlights the influence of calcium channels on tumorigenesis and progression. Hence, inhibition of calcium signaling may be a promising cancer treatment strategy. OBJECTIVE: In this study, we aimed to examine whether calcium channel blockers (CCBs) affect the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). DESIGN: We conducted a retrospective analysis. METHODS: In this study, conducted between January 2009 and June 2021, patients with NSCLC treated with erlotinib, or gefitinib for at least 1 week were enrolled and divided into 2 groups: CCBs-/EGFR-TKIs+ and CCBs+/EGFR-TKIs+, depending on whether they received CCB therapy. Progression-free survival (PFS) and overall survival (OS) were determined as the primary and secondary endpoints, respectively. RESULT: : The estimated median PFS and OS for the CCBs-/EGFR-TKIs+group were 7.70 and 12.17 months, respectively, and they were significantly different from those of the CCBs+/EGFR-TKIs+ group (10.43 and 18.07 months, respectively). CCB use was associated with improved PFS (adjusted hazard ratios [HR] 0.77, 95% confidence interval [CI]: 0.61-0.98; P = .035) and OS (adjusted HR 0.66, 95% CI: 0.51-0.84; P < .001). CONCLUSION: Calcium channels have been implicated in cancer pathogenesis. Our findings revealed the potential additive anticancer effects of CCBs when used concomitantly with EGFR-TKIs. However, study limitations, including the retrospective nature and small number of patients, necessitate large-scale prospective studies on the therapeutic potential of CCB as an adjunctive therapy with EGFR-TKIs in patients with NSCLC.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Retrospectivos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias Pulmonares/metabolismo , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Receptores ErbB/metabolismo , Mutação , Canais de Cálcio/uso terapêuticoRESUMO
BACKGROUND: This retrospective cohort study examined the impact of tetracyclines (TCs) and proton pump inhibitors (PPIs) alone or in combination on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC treated with gefitinib or erlotinib for at least 1 week between January 2009 and October 2021 were enrolled and divided into four groups based on the presence/absence of TC and/or PPI in the therapeutic regimen: TC-/PPI-, TC + /PPI-, TC-/PPI + , TC + /PPI + . Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. RESULTS: The estimated median PFS and OS of 347 included patients with NSCLC were 8.57 (95% confidence interval [CI]: 7.66-9.48) months and 13.10 (95% CI: 11.03-15.17) months, respectively. Co-administration of EGFR-TKIs with PPIs decreased the PFS and OS, while that with TCs improved the PFS and OS. However, the concomitant use of EGFR-TKIs, TCs, and PPIs yielded survival rates similar to that of EGFR-TKI therapy alone. CONCLUSIONS: The administration of EGFR-TKIs with other drugs poses a challenge in managing patients with NSCLC. Therefore, reassessing the indications and necessity of TC or PPI therapy is essential for patients receiving erlotinib or gefitinib. The benefits and risks of possible discontinuation due to the clinical relevance of this interaction should be considered.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Quinazolinas , Estudos Retrospectivos , Tetraciclinas/uso terapêuticoRESUMO
Coronavirus disease 2019 (COVID-19) pandemic is currently the most serious public health threat faced by mankind. Thus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is being intensively investigated. Several vaccines are now available for clinical use. However, owing to the highly mutated nature of RNA viruses, the SARS-CoV-2 is changing at a rapid speed. Breakthrough infections by SARS-CoV-2 variants have been seen in vaccinated individuals. As a result, effective therapeutics for treating COVID-19 patients is urgently required. With the advance of computer technology, computational methods have become increasingly powerful in the biomedical research and pharmaceutical drug discovery. The applications of these techniques have largely reduced the costs and simplified processes of pharmaceutical drug developments. Intensive and extensive studies on SARS-CoV-2 proteins have been carried out and three-dimensional structures of the major SARS-CoV-2 proteins have been resolved and deposited in the Protein Data Bank. These structures provide the foundations for drug discovery and design using the structure-based computations, such as molecular docking and molecular dynamics simulations. In this review, introduction to the applications of computational methods in the discovery and design of novel drugs and repurposing of existing drugs for the treatments of COVID-19 is given. The examples of computer-aided investigations and screening of COVID-19 effective therapeutic compounds, functional peptides, as well as effective molecules from the herb medicines are discussed.
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Patients with inflammatory bowel disease (IBD) present a higher risk of developing cardiovascular diseases (CVDs) due to chronic inflammation, which plays an essential role in atherogenesis. Hyperlipidemia is another risk factor for CVDs; however, the association between IBD, IBD medications, and hyperlipidemia remains controversial. We conducted a nationwide, population-based, retrospective, cohort study to examine the effect of IBD and IBD medications on the risk of developing hyperlipidemia. The effects of IBD medications on the expression of lipogenesis-related hepatic genes were also evaluated. We obtained data from the Longitudinal Health Insurance Database of Taiwan from patients with new-onset IBD and a comparison cohort of patients without IBD. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing hyperlipidemia between the two cohorts. We also examined the influence of IBD medications on the expression of lipogenesis-related hepatic genes. After adjusting for comorbidities and confounding factors, the case group (N = 14,524) had a higher risk for hyperlipidemia than the control group (N = 14,524) [adjusted hazards ratio (aHR), 2.18]. Patients with IBD that did not receive IBD medications exhibited a significantly higher risk of hyperlipidemia (aHR, 2.20). In those treated with IBD medications, the risk of developing hyperlipidemia was significantly lowered than those without such medications (all aHR ≤ 0.45). Gene expression analysis indicated that IBD medications downregulated the expression of lipogenesis-related genes. Screening blood lipids in IBD patients is needed to explore the specific role and impact of IBD medications in the development of CVD.
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Paclitaxel is a prescribed anticancer drug used to treat various cancers. It is a substrate of cytochrome P-450 (CYP-450) enzymes. Despite its efficacy, paclitaxel has severe side effects. Herbal medicines are commonly used to treat the side effects of chemotherapy. They can be administered before, during, and after chemotherapy. Xiang-Sha-Liu-Jun-Zi Tang (XSLJZT) is a herbal formula commonly used in breast cancer patients. The main purpose of this study was to assess the pharmacokinetic (PK) influence of XSLJZT on paclitaxel PK parameters, determine its effect on CYP-450 enzyme expression, and evaluate its effect on enzyme activity. Sprague Dawley rats were classified into pretreatment and co-treatment groups, where XSLJZT was pre-administered for 3, 5, and 7 days and co-administered 2 h before paclitaxel administration. The rat liver tissues and Hep-G2 cells were used to determine the effects of XSLJZT on CYP3A1/2 and CYP3A4 enzymes respectively. Western blot analysis was used to detect changes in the CYP3A1/2 and CYP3A4 enzymes expression. The influence of XSLJZT on enzyme activity was evaluated using human liver microsomes, and a liquid chromatography-tandem mass spectrometric system was developed to monitor paclitaxel levels in rat plasma. Results demonstrated that XSLJZT increased the area under the concentration versus time curve (AUC) for paclitaxel in pretreatment groups by 2-, 3-, and 4-fold after 3, 5, and 7 days, respectively. In contrast, no significant change in the AUC was observed in the co-treatment group. However, the half-life was prolonged in all groups from 17.11 min to a maximum of 37.56 min. XSLJZT inhibited CYP3A1/2 expression in the rat liver tissues and CYP3A4 enzymes in Hep-G2 cells in a time-dependent manner, with the highest inhibition observed after 7 days of pretreatment in rat liver tissues. In the enzyme kinetics study, XSLJZT inhibited enzyme activity in a competitive dose-dependent manner. In conclusion, there is a potential interaction between XSLJZT and paclitaxel at different co-treatment and pretreatment time points.
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BACKGROUND: Tigecycline is an antibiotic that well tolerated for treating complicated infections. It has received attention as an anti-cancer agent and expected to solve two major obstacles, sides effects that accompany chemotherapy and drug resistance, in the breast cancer treatment. However, previous studies reported that the levels in the blood are typically low of tigecycline, so higher doses are needed to treat cancer, that may increase the risk of side effects. To achieve better anti-cancer effects for tigecycline, we need to find a novel adjunct agent. METHODS: In this study, we used different concentration of pyrvinium pamoate combined with tigecycline to treat cell. And assess the effect of two drugs in inhibit cell proliferation, induce cell autophagy, or increase cell apoptosis to evaluate the consequent of combined therapy. RESULTS: We observed that after the combined therapy, the cell cycle arrest at G1/s phase, the level of p21 increased, but decreased the levels of CDK2. Others, two drugs via different mechanisms to inhibit cancer cell proliferation and with selective cytotoxic to different cell lines. That could enhance the effect of breast cancer treatment. CONCLUSION: Combining low dose of tigecycline use with pyrvinium pamoate is a novel approach for breast cancer treatment. Appropriate combined therapy in breast cancer is recommended to improve outcomes. Other problems like drug resistance occur in patients or the microbes surrounding breast tissues would confer susceptibility to cancers then influence the effectiveness of treatment, which could be improved through combined therapy.
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Neoplasias da Mama , Doenças Transmissíveis , Compostos de Pirvínio , Neoplasias da Mama/tratamento farmacológico , Doenças Transmissíveis/tratamento farmacológico , Feminino , Humanos , Compostos de Pirvínio/farmacologia , Compostos de Pirvínio/uso terapêutico , TigeciclinaRESUMO
ABSTRACT: The purpose of this study was to evaluate the clinical outcomes, including patient prognosis and medication expense, of proton pump inhibitors administered by high-dose continuous infusion (HDC, 80âmg loading dose, then 8âmg/h for 72âhours) or non-high-dose intermittent infusion (NHDI, 40âmg qd or 40âmg q12âh, for 3âdays) regimens in high-risk patients with bleeding peptic ulcers.In this retrospective cohort study, patients with peptic ulcers and endoscopic hemostasis between January, 2013 and December, 2015 were included. The primary endpoints were rebleeding and mortality rates within 7âdays. The secondary endpoints were length of stay (LOS), transfusion units of packed red blood cells (PRBCs), and the number needed to treat.A total of 335 patients met the inclusion criteria during the 3-year follow-up period. The cumulative incidence of rebleeding within 7âdays was 20.4% and 11.2% in the HDC and NHDI groups, respectively, with a significant difference (Pâ=â.021). The mortality rate was 12.1% and 7.3% in the HDC and NHDI groups, respectively, with no significant difference (Pâ=â.136). Univariate Cox proportional hazards model analysis showed that the risk of rebleeding within 7âdays in the HDC group was higher than that in the NHDI group. The hazard ratio for HDC vs. NHDI was 1.93 (Pâ=â.021). There were significant differences in LOS (Pâ=â.034) and PRBC units (Pâ=â.005) for risk of rebleeding within 7âdays, as well as in transfusion units of PRBCs for mortality rate analysis (pâ<â0.001), between the HDC and NHDI groups. The results showed that the NHDI regimen could reduce the risk of rebleeding within 7âdays in 1 of 11 patients (number needed to treatâ=â11) and could reduce medication cost by US$ 400 to 800.The NHDI regimen showed a lower risk of rebleeding within 7âdays, shorter LOS, and fewer PRBC units than that of the HDC regimen. Receiving NHDI has better cost-effective outcomes than that of HDC for patients with high-risk bleeding peptic ulcers.
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Anemia Ferropriva , Hemostase Endoscópica , Inibidores da Bomba de Prótons/economia , Idoso , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/complicações , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica Hemorrágica/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Depression increases the risk of cardiovascular disease (CVD). The association between antidepressant medications (ADMs) and CVD remains controversial. Hyperlipidemia is a risk factor for CVD. We conducted a nationwide population-based retrospective cohort study to examine depression and ADM use on the risk of developing hyperlipidemia. The effects of ADMs on the expression of lipogenesis-related hepatic genes were also evaluated. METHODS: We obtained data from the Longitudinal Health Insurance Database of Taiwan on patients with new-onset depression and a comparison cohort without depression. A Cox proportional hazards regression model was used to analyze the differences in the risk of developing hyperlipidemia between these two cohorts. We also examined the influence of ADMs on the expression of lipogenesis-related hepatic genes. RESULTS: After adjustment for comorbidities and confounding factors, the case group (N = 38,322) had a higher risk for hyperlipidemia than that of the control cohort (N = 38,322) [adjusted hazards ratio (aHR) =1.16]. Patients with depression who did not receive ADM therapy exhibited a significantly higher risk of hyperlipidemia (aHR = 1.61). However, in patients with depression treated with ADMs, the risk of developing hyperlipidemia was significantly lowered compared to the patients without ADMs (all aHR < 0.81). Gene expression analysis indicated that ADMs downregulated the expression of lipogenesis-related hepatic genes. LIMITATIONS: Unmeasured confounding risk factors for hyperlipidemia might not have been included in the study. CONCLUSIONS: ADMs reduced hyperlipidemia risk in patients with depression, partly by downregulating the expression of lipogenesis-related genes and improving the patients' lipid profiles. Early diagnosis and management of hyperlipidemia would further facilitate the prevention of CVD.
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Hiperlipidemias , Antidepressivos , Estudos de Coortes , Comorbidade , Depressão/epidemiologia , Depressão/genética , Expressão Gênica , Humanos , Hiperlipidemias/epidemiologia , Hiperlipidemias/genética , Incidência , Lipogênese/genética , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
The relationship between depression, antidepressant medications (ADMs), and the risk of subsequent type 2 diabetes mellitus (T2DM) development remains controversial. Thus, we investigated this aspect by a population-based retrospective cohort study using the Longitudinal Health Insurance Database 2000 available in Taiwan. This large, observational study included 46,201 patients with depression and a 1 : 1 age- and sex-matched nondepression cohort enrolled between January 1, 2000, and December 31, 2013, and the newly diagnosed T2DM incidence rates were determined. We estimated the effects of depression on T2DM and the cumulative incidence curves by Cox proportional regression hazard models and Kaplan-Meier methods, respectively. We found that 47.97% of the patients with depression did not receive ADM. Among patients with depression who received ADM, 29.71%, 6.29%, 0.05%, 9.65%, and 6.32% received selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), heterocyclic antidepressants, and other medications, respectively. Patients without ADM treatment had a 39% higher risk of developing T2DM. However, those who received ADM treatment had a significantly lower risk of T2DM development in every treatment category. Depressive disorder treated with ADMs, especially with long-term use, was associated with an 11-48% decrease in the risk of T2DM in all ADM groups; however, heterocyclic antidepressant treatment for shorter periods (<80 days) was not significantly associated with a decreased risk of T2DM. The incidence of T2DM in Taiwan was found to be associated with an a priori history of depression and was inversely correlated with ADM treatment.
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Antidepressivos/uso terapêutico , Depressão , Diabetes Mellitus Tipo 2 , Adulto , Idoso , Comorbidade , Depressão/complicações , Depressão/tratamento farmacológico , Depressão/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , TaiwanRESUMO
OBJECTIVE: Cryptotanshinone (CPT) and dihydrotanshinone (DHT) are diterpenoid anthraquinone compounds extracted from traditional Chinese herbal medicine (TCM). Recent studies have shown that CPT regulates the signal transduction pathways via microRNA (miRNA) alterations. However, few studies have investigated the role of DHT in miRNA alterations affecting cell-signaling pathways. This study aimed to investigate the miRNA alterations and post-transcriptional regulation activities of DHT in comparison to CPT. METHODS: HepG2 and HT-29 cells were treated with DHT or CPT for 72 h. MiRNA, transcription factor encoding mRNA, and downstream gene expression were determined using real-time quantitative PCR. Protein expression was analyzed using western blotting. RESULTS: The results revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via miR-15a-5p, miR-27a-5p, miR-100-5p, and miR-200a-5p alterations.In silico target predictions showed that downregulation of epidermal growth factor receptor (EGFR) mRNA expression by DHT might also suppress the expression of STAT family proteins and lead to anti-proliferation effects. We also found that, compared to CPT, DHT might possess higher potency in cell growth regulation via multi-miRNA and transcription factor alterations. CONCLUSION: This study revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via alterations in miRNAs and transcription factors. In addition, the findings of this study suggest that DHT is more potent than CPT in cancer chemopreventive activities. Therefore, DHT at a low dose is a TCM compound with less toxic side effects and may contribute to the development of natural medicine as a potential cancer chemopreventive agent.
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Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Furanos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/metabolismo , Fenantrenos/farmacologia , Quinonas/farmacologia , Transcriptoma/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Células HT29 , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Hepatitis B virus carriers who receive systemic cancer chemotherapy have been found to be at a higher risk of hepatitis B virus reactivation. However, lack of standard prophylaxis protocol resulted in life-threatening adverse events. OBJECTIVE: This retrospective study is to investigate prevalence and chemotherapy drug-induced hepatitis B virus reactivation in all types of cancer patients and establish an institutional clinical practice protocol.Methodology: This retrospective cohort study evaluated the incidence of hepatitis B virus infection, the pre-chemotherapy screening rate of hepatitis B surface antigen (HBsAg), and the severity of hepatitis B virus reactivation of cancer patients receiving intravenous chemotherapy between 2013 and 2014. Patients receiving local chemotherapy with intra-cavity instillation, drug- or alcohol-related hepatitis, or chemotherapy for immune diseases were excluded. RESULTS: In total 784 patients, 404 patients (51.53%) underwent hepatitis B virus serum antigen (HBsAg) testing before chemotherapy, and 61 patients (7.78%) tested positive. Only 32 patients (4.08%) received prophylactic hepatitis B virus antiviral therapy. Patients receiving prophylactic antiviral drugs were significantly lower risk of hepatitis B virus reactivation than nonprophylaxis (relative risk, RR: 0.53, number needed to treat, NNT: 12). Moreover, our study found specific single or combined chemotherapy that may cause hepatitis B virus reactivation different from those of other studies conducted in Western countries. The differences may refer to enzymes, proteins and immune response of patients. CONCLUSIONS: Our findings indicate that cancer patients receiving prophylactic antiviral drugs remain at risk of hepatitis B virus reactivation during chemotherapy. Therefore, the hepatitis B virus screen and chemotherapy control system was established in 2017 to reduce the risk of hepatitis B virus reactivation and improve patient safety.
Assuntos
Vírus da Hepatite B , Hepatite B/complicações , Hepatite B/epidemiologia , Neoplasias/complicações , Neoplasias/epidemiologia , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Feminino , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/análise , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
Patients with gout are at a higher risk of cardiovascular disease, which is associated with hyperlipidemia. Management of gout in Taiwan is poor, and the association between urate-lowering therapy (ULT) among gout patients and hyperlipidemia is unclear. We conducted a retrospective cohort study using data from the Longitudinal Health Insurance Database (LHID) of Taiwan on new-onset gout patients and a comparison cohort without gout. A Cox proportional hazards model was used to analyze differences in the risk of hyperlipidemia between patients with and without gout after considering related comorbidities. We also examined the ULT medications on the hepatic expression of lipogenesis-related genes. After adjusting for potential confounders, the case group (44,413 patients) was found to have a higher risk of hyperlipidemia than the control cohort (177,652 patients) [adjusted hazards ratio (aHR) = 2.55]. Gout patients without antigout treatment had significantly higher risk of hyperlipidemia than the control cohort (aHR = 3.10). Among gout patients receiving ULT, except those receiving probenecid (aHR = 0.80), all had significantly lower risk of hyperlipidemia than gout patients without ULT (all aHR < 0.90). Using real-time polymerase chain reaction, we found that most of the antigout drugs decreased the expression of hepatic genes related to lipogenesis in differentiated HepaRG cells. These data indicate that these antigout drugs reduce hyperlipidemia in gout patients, partly via the reduction in expression of lipogenesis-related genes, leading to improved blood lipid profiles. We provide evidence of the strong association between gout and hyperlipidemia and highlight the need for appropriate treatment guidelines.
Assuntos
Gota/tratamento farmacológico , Gota/metabolismo , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ácido Úrico/química , Adulto , Estudos de Coortes , Feminino , Células Hep G2 , Humanos , Incidência , Estimativa de Kaplan-Meier , Lipídeos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , TaiwanRESUMO
There have been no reports on the association of hyperthyroidism with hyperlipidemia in patients undergoing treatment especially in Asia. To determine the association between hyperthyroidism and the risk of hyperlipidemia in patients, we conducted a retrospective cohort study using Longitudinal Health Insurance Database (LHID) from Taiwan, R.O.C. We also evaluate the influence of 6-n-propyl-2-thiouracil (PTU) and methimazole (MMI) on hepatic genes to explain changes in blood lipid levels in a hepatic cell line model. The cohort study involved 13,667 patients with hyperthyroidism, and the corresponding comparison cohort had four times as many patients. Using Kaplan-Meier analysis method, the results showed that, compared to patients without hyperthyroidism, the overall incidence of hyperlipidemia was significantly higher in the hyperthyroidism patients (18.7 vs. 11.8 cases/1,000 persons-years; adjusted HR 1.5; 95% CI, 1.41-1.59). With only PTU or MMI/carbimazole (CBM) treatment, patients with hyperthyroidism showed a 1.78-fold (95% CI, 1.50-2.11) and 1.43-fold (95% CI, 1.27-1.60) higher risk of hyperlipidemia than those without hyperthyroidism, respectively. Additionally, hyperthyroidism patients that received surgery only or surgery with I131 therapy tended to have a higher risk of hyperlipidemia. Although PTU and MMI treatment decreased the expression levels of genes responsible for circulating remnant lipoproteins, they increased the levels of lipogenic gene expression in hepatic cells. Thus, treatment of hyperthyroid patients with anti-thyroid drugs (ATDs), I131, or surgery is likely to induce hyperlipidemia. ATDs downregulate the expression of genes involved in lipoproteins clearance; increases lipogenic genes expression, which may partly contribute to abnormal blood lipid profiles.
RESUMO
Oxidative stress plays a critical role in the pathogenesis of hearing loss, and 2,3,4',5-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) exerts antioxidant effects by inhibiting reactive oxygen species (ROS) generation. With the aim of developing new therapeutic strategies for oxidative stress, this study investigated the protective mechanism of THSG in vitro using a normal mouse cochlear cell line (UB/OC-2). The THSG and ascorbic acid have similar free radical scavenger capacities. H2O2, but not THSG, reduced the UB/OC-2 cell viability. Moreover, H2O2 might induce apoptosis and autophagy by inducing morphological changes, as visualized by microscopy. As evidenced by Western blot analysis and monodansylcadaverine (MDC) staining, THSG might decrease H2O2-induced autophagy. According to a Western blotting analysis and Annexin V/PI and JC-1 staining, THSG might protect cells from H2O2-induced apoptosis and stabilize the mitochondrial membrane potential. Furthermore, THSG enhanced the translocation of nucleus factor erythroid 2-related factor 2 (Nrf2) into the nucleus and increased the mRNA and protein expression of antioxidant/detoxifying enzymes under H2O2-induced oxidative stress conditions. Collectively, our findings demonstrate that THSG, as a scavenging agent, can directly attenuate free radicals and upregulate antioxidant/detoxifying enzymes to protect against oxidative damage and show that THSG protects UB/OC-2 cells from H2O2-induced autophagy and apoptosis in vitro.