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Osimertinib (AZD9291) has been widely used for the treatment of EGFR mutant non-small cell lung cancer. However, resistance to osimertinib is inevitable. In this study we elucidated the molecular mechanisms of resistance in osimertinib-resistant NCI-H1975/OSIR cells. We showed that NCI-H1975/OSIR cells underwent epithelial-mesenchymal transition (EMT), which conferred sensitivity to the GPX4 inhibitor 1S, 3R-RSL3 to induce ferroptotic cell death. The EMT occurrence resulted from osimertinib-induced upregulation of TGFß2 that activated SMAD2. On the other hand, we revealed that NCI-H1975/OSIR cells were highly dependent on NF-κB pathway for survival, since treatment with the NF-κB pathway inhibitor BAY 11-7082 or genetic silence of p65 caused much greater cell death as compared with the parental NCI-H1975 cells. In NCI-H1975 cells, osimertinib activated NF-κB pathway, evidenced by the increased p65 nuclear translocation, which was abolished by knockdown of TGFß2. In the cancer genome atlas lung adenocarcinoma data, TGFB2 transcript abundance significantly correlated with EMT-associated genes and NF-κB pathway. In addition, coexistence of EMT and activation of NF-κB pathway was observed in several NCI-H1975/OSIR clones. These findings shed new light on distinct roles of TGFß2 in osimertinib-resistant cells and provide new strategies for treatment of this resistant status.
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Acrilamidas/farmacología , Compuestos de Anilina/farmacología , Resistencia a Antineoplásicos/fisiología , Transición Epitelial-Mesenquimal/fisiología , Subunidad p50 de NF-kappa B/metabolismo , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Antineoplásicos/farmacología , Carbolinas/farmacología , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismoRESUMEN
A cobalt(II)-catalyzed coupling-cyclization cascade reaction between tryptamine-derived isocyanides and iodonium ylides is investigated, which allowed for the synthesis of different types of spiroindoline compounds by variation of substituents at the N1- and C2-positions in the indole skeleton. More interesting is that the spiroindoline products could undergo despirocyclization in the presence of amines, enabling efficient construction of enamine compounds.
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Aims: We aimed to explore the role of personality traits between fall and loneliness. Methods: A questionnaire survey was used to investigate falls, the big five personality traits, and loneliness among older people (≥ 60 years old) in China mainland. Results: A total of 4,289 older people participated in the survey. There are significant differences in age, marital status, education level, residence, solitariness, and fall in relation to loneliness among older people. Falls, especially when they occurred one time increase the loneliness of older people. Agreeableness, conscientiousness, and neuroticism were significant mediating effects between falls and loneliness. Conclusion: This study implied that agreeableness, conscientiousness, and neuroticism were meditating factors between falls and loneliness. In the future, we should consider the big five personality traits more to understand loneliness and offer older people interventions for reducing their loneliness. The study design was cross-sectional, so the temporal precedence of mediators and causality could not be tested. Because the data were collected retrospectively, current loneliness is likely to have confounding effects on retrospective recall.
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BACKGROUND: Previous studies indicated that type 2 diabetes mellitus (T2DM) might be associated with the risk of cancer. The aim of this study was to investigate the association between T2DM and the risk of developing common cancers in a Chinese population. METHODS: A population-based retrospective cohort study was carried out in the Nan-Hu district of Jiaxing city, Zhejiang province, China. The incidence of cancer cases among type 2 diabetic patients were identified through record-linkage of the Diabetic Surveillance and Registry Database with the Cancer Database from January 2002 to June 2008. The standardized incidence ratio (SIR) and 95% confidence interval (CI) were estimated for the risk of cancer among the patients with type 2 diabetes. RESULTS: The overall incidence of cancer was 1083.6 per 10(5) subjects in male T2DM patients and 870.2 per 105 in females. Increased risk of developing cancer was found in both male and female T2DM patients with an SIR of 1.331 (95% CI = 1.143-1.518) and 1.737 (1.478-1.997), respectively. As for cancer subtypes, both male and female T2DM patients had a significantly increased risk of pancreatic cancer with the SIRs of 2.973 (1.73-4.21) and 2.687 (1.445-3.928), respectively. Elevated risk of liver and kidney cancers was only found in male T2DM patients with SIRs of 1.538 (1.005-2.072) and 4.091 (1.418-6.764), respectively. Increased risks of developing breast cancer [2.209 (1.487-2.93)] and leukemia SIR: [4.167 (1.584- 6.749) ] were found in female patients. CONCLUSIONS: These findings indicated that patients with T2DM have an increased risk of developing cancer. Additional cancer screening should be employed in the management of patients with T2DM.
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Diabetes Mellitus Tipo 2/complicaciones , Neoplasias/etiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , China/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Detección Precoz del Cáncer , Femenino , Humanos , Incidencia , Neoplasias Renales/epidemiología , Neoplasias Renales/etiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/etiología , Vigilancia de la Población , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
Yes-associated protein 1 (YAP1) is involved in the development of a variety of malignancies. However, the prognosis of malignant digestive tumors with YAP1 expression is still controversial. This study searched 31 articles with 36 data sets of 4023 patients to explore the role of YAP1 expression on the prognosis of digestive malignant tumors by searching the PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library databases. Specifically, relevant cancer expression matrix data were downloaded from The Cancer Genome Atlas (TCGA) database. In this meta-analysis, quantitative analysis showed that the overexpression of YAP1 was not conducive to OS (1.62, 95% CI (1.38, 1.90), P=0.001) and DFS (1.59, 95% CI (1.31, 1.93), P=0.001) in patients with digestive malignant tumors. In addition, TCGA database analysis showed that YAP1 was overexpressed in gastric cancer, cholangiocarcinoma, and colorectal cancer. Survival analysis showed that the patients with high expression of YAP1 in pancreatic cancer have a poor OS (MST: 394 vs. 691 days, P < 0.0001) and DFS (MST: 371 vs. 542 days, P=0.026) prognosis. YAP1 may be a molecular marker that effectively predicts the survival of malignant digestive tumors, especially pancreatic cancer, and is a potential therapeutic target for malignant digestive tumors.
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Lung cancer is the leading cause of cancer death worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Metastasis is the major cause of poor prognosis and mortality for lung cancer patients, which urgently needs great efforts to be further explored. Herein, glutathione peroxidase 8 (GPX8) was identified as a novel potential pro-metastatic gene in LUAD metastatic mice models from GEO database. GPX8 was highly expressed in tumor tissues, predicting poor prognosis in LUAD patients. Knockdown of GPX8 inhibited LUAD metastasis in vitro and in vivo, while it did not obviously affect tumor growth. Knockdown of GPX8 decreased the levels of p-FAK and p-Paxillin and disturbed the distribution of focal adhesion. Furthermore, GPX8 was overexpressed in cancer-associated fibroblast (CAF) and associated with CAF infiltration in tumor microenvironment of lung cancer. GPX8 silence on fibroblasts suppressed lung cancer cell migration in the coculture system. BRD2 and RRD4 were the potential transcriptionally regulators for GPX8. Bromodomain extra-terminal inhibitor JQ1 downregulated GPX8 expression and suppressed lung cancer cell migration. Our findings indicate that highly expressed GPX8 in lung cancer cells and fibroblasts functions as a pro-metastatic factor in lung cancer. JQ1 is identified as a potential inhibitor against GPX8-mediated lung cancer metastasis.
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Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.
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Antígeno B7-H1/antagonistas & inhibidores , Flavonoides/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Interferón gamma/farmacología , Neoplasias Pulmonares/metabolismo , Células A549 , Antígeno B7-H1/biosíntesis , Antígeno B7-H1/genética , Técnicas de Cocultivo , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/fisiología , Células HCT116 , Células HEK293 , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/biosíntesis , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Células Jurkat , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/fisiologíaRESUMEN
The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.
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One new flavanonol 4 H-â1-âbenzopyran-â4-âone,2-â(4-âhydroxyphenyl)â-â3,â7-âdihydroxy-â5-âmethoxy-â8-â[5-âmethyl-â2-â(1-âmethylethenyl)â-â4-âhexenyl]â(21), and twenty-six known compounds 1-20, 22-27 were isolated from the dried root of Sophora flavescens (S. flavescens) in this chemical study. Their structures were elucidated according to the spectroscopic and spectrometric methods. All the isolated compounds were evaluated for their cytotoxicity against lung cancer A549 cells and colon cancer HCT116 cells. Among them, compound 21 showed relatively predominant cell proliferation inhibition effect on the two tumor cell lines. Moreover, it induced cells apoptosis as evidenced by the Annexin V/PI double staining assay as well as the increased cleaved-PARP expression. The aforementioned data indicated that the flavonoids of S. flavescens have potential anti-cancer effect.
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Antineoplásicos , Neoplasias , Sophora , Flavonoides/farmacología , Extractos Vegetales/farmacología , Raíces de Plantas , Análisis EspectralRESUMEN
The anti-phagocytosis signal, CD47, prevents phagocytosis when it interacts with signal-regulatory protein alpha (SIRPα) on macrophages. Given the vital role of CD47 in immune response, further investigation on the regulation of CD47 in tumor microenvironment is needed. Herein, we identified that interferon-gamma (IFN-γ), one of the most important cytokines in the immune and inflammatory response, up-regulated CD47 expression in cancer cells and this effect could be inhibited by the JAK1/2 inhibitor ruxolitinib, as well as siRNA-mediated silencing of JAK1, STAT1, and IRF1. The IFN-γ-induced surface expression of CD47 contributed to a stronger binding affinity to SIRPα and a decrease in phagocytosis of cancer cells by macrophages. Knockdown of JAK1, STAT1, or IRF1 by siRNA reversed the decreased phagocytosis caused by IFN-γ. Besides, analysis from TCGA revealed that IFNG had a positive correlation with CD47 in various types of cancer, which was supported by the increased surface CD47 expression after IFN-γ treatment in different types of cancer cells. The discovery of IFN-γ-induced up-regulation of CD47 in cancer cells unveils another feedback inhibitory mechanism of IFN-γ, thus providing insights into cancer immunotherapy targeting CD47.
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BACKGROUND: Programmed death-ligand 1 (PD-L1), which can be induced by interferon-gamma (IFN-γ) in the tumor microenvironment, is a critical immune checkpoint in cancer immunotherapy. Natural products which reduce IFN-γ-induced PD-L1 might be exert immunotherapy effect. Licochalcone A (LCA), a natural compound derived from the root of Glycyrrhiza inflata Batalin. (Fabaceae), was found to interfere IFN-γ-induced PD-L1. PURPOSE: The aim of this study is to further clarify the effect and the mechanism of LCA on inhibiting IFN-γ-induced PD-L1 in lung cancer cells. METHODS: The expression levels of PD-L1 were evaluated by flow cytometry, western blot and qRT-PCR. Click-iT protein synthesis assay and luciferase assay were used to identify the effect of LCA on protein synthesis. Jurkat T cell proliferation and apoptosis in the co-culture system were detected by flow cytometry. Flow cytometry was also applied to evaluate reactive oxygen species (ROS) generation. RESULTS: LCA downregulated IFN-γ-induced PD-L1 protein expression and membrane localization in human lung cancer cells, regardless of inhibiting PD-L1 mRNA level or promoting its protein degradation. LCA decreased apoptosis and proliferative inhibition of Jurkat T cells caused by IFN-γ-induced PD-L1-expressing in A549 cells in the co-culture system. Strikingly, LCA was verified as a protein synthesis inhibitor, which reduced both cap-dependent and -independent translation. LCA inhibited PD-L1 translation, likely due to inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α pathway. Furthermore, LCA induced ROS generation in a time-dependent manner in lung cancer cells. N-acetyl-L-cysteine (NAC) not only revered ROS generation triggered by LCA but also restored IFN-γ-induced expression of PD-L1. Both the inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α axis triggered by LCA was restored by co-treatment with NAC. CONCLUSION: LCA abrogated IFN-γ-induced PD-L1 expression via ROS generation to abolish the protein translation, indicating that LCA has the potential to be applied in cancer immunotherapy.
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Antineoplásicos Fitogénicos/farmacología , Antígeno B7-H1/metabolismo , Chalconas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis/efectos de los fármacos , Antígeno B7-H1/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Interferón gamma/metabolismo , Interferón gamma/farmacología , Células Jurkat , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Fosforilación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Escape del Tumor/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacosRESUMEN
Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.
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Antineoplásicos/farmacología , Antígeno B7-H1/metabolismo , Diterpenos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lactonas/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Diterpenos/química , Humanos , Lactonas/química , Estructura MolecularRESUMEN
BackgroundNarrative exposure therapy (NET), an integration of narrative therapy and exposure therapy, has been shown to be effective in relieving the symptoms of post-traumatic stress disorder (PTSD), which can help patients gain a deeper understanding of their trauma and is also considered to be quite safe. PTSD is highly prevalent in children and adolescents, while the effectiveness of NET intervention varies among the subjects. ObjectiveTo systematically evaluate the effectiveness of NET for PTSD in children and adolescents, so as to provide references for the clinical application of NET. MethodsOn August 1, 2022, the Cochrane Library, PubMed, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI), SinoMed, VIP and Wanfang database were searched from their inception to June 2022. Search was conducted with the use of a combination of medical subject heading and free text terms, and randomized controlled trials relevant to NET for PTSD in children and adolescents were collected. Then the quality of the controlled trials was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias (2011), and Meta-analysis was performed using RevMan 5.4 software. ResultsNine randomized controlled trials involving 394 children and adolescents with PTSD were included. Meta-analysis showed that NET and relaxation therapy reported comparable symptom relief in PTSD patients within 1 to 3 months after intervention (SMD=0.22, 95% CI: -0.84~1.28) and at 6 months after intervention (SMD=0.21, 95% CI: -0.75~1.17), while NET provided greater PTSD symptom relief than routine therapy both within 1 to 3 months after intervention (SMD=-0.66, 95% CI: -1.04~-0.27) and at 6 months after intervention (SMD=-0.77, 95% CI: -1.36~-0.19), with statistically significant differences. Regarding the alleviation of depressive symptoms, the effect was similar between NET and routine therapy within 1 to 3 months after intervention (SMD=-0.39, 95% CI: -0.98~0.21) and at 6 months after intervention (SMD=-0.74, 95% CI: -2.23~0.75). No statistical difference was demonstrated between NET and routine therapy in relieving psychological distress (SMD=-0.54, 95% CI: -2.14~1.07) and suppressing hyperorexia (SMD=-0.17, 95% CI: -0.54~0.19) 1 to 3 months after intervention. ConclusionNET yields a better outcome and a medium- and long-term effectiveness in alleviating symptoms of PTSD in children and adolescents compared with routine therapy, while it does not offer any significant advantages in improving depression symptoms, psychological distress and hyperorexia.
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Objective To explore the medication rules of Professor ZHONG Guang-Ling's prescriptions for the treatment of lumbar disc herniation(LDH)based on data mining method,so as to provide reference for the treatment of LDH with Chinese medicine.Methods The prescriptions for the effective cases of outpatients of LDH treated by Professor ZHONG Guang-Ling in the recent 5 years were collected.The medication frequency of Chinese medicines in the included prescriptions and the distribution of their properties,flavors and meridian tropism were investigated.Moreover,the association rule analysis and cluster analysis of the high-frequency drugs were carried out.Results A total of 164 prescriptions were included and 168 Chinese medicines were used.The top 10 high-frequency drugs in descending order were Achyranthis Bidentatae Radix,Chuanxiong Rhizoma,Pheretima,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Gentianae Macrophyllae Radix,Angelicae Sinensis Radix,Rehmanniae Radix Praeparata,Persicae Semen,Cyperi Rhizoma,and Carthami Flos.The properties of the prescribed drug were mainly warm and mild in nature,and bitter and pungent in flavor,and mainly had the meridian tropism of the liver,kidney and spleen meridians.According to the therapeutic actions,the drugs were mainly categorized as deficiency-supplementing drugs,dampness-removing and collateral-unblocking drugs,and blood-activating and stasis-removing drugs.The results of association rule analysis yielded 10 drug pairs,and cluster analysis yielded 6 core drug combinations.Conclusion For the treatment of LDH,Professor ZHONG Guang-Ling usually adopts the Chinese medicine for supplementing the deficiency and supporting healthy-qi,together with the medicines for nourishing the liver and kidney and regulating the spleen and stomach from the perspective of liver,kidney and spleen.Moreover,therapy of activating blood and removing stasis is also stressed,pathogen-eliminating medicines for removing dampness,unblocking collaterals and clearing heat are used based on syndrome differentiation,and then simultaneous application of purging and nourishing therapeutics is achieved through the utilization of purging method after supplementing method.
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In cardiovascular disorders, neurological diseases, and chronic metabolic diseases, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is essential for maintaining cell homeostasis. According to studies, boosting Nrf2 expression can be used to cure or prevent chronic diseases that are characterized by oxidative stress, inflammation, and mitochondrial dysfunction. Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease characterized by hepatic steatosis brought on by a number of causes other than alcohol. In recent years, its incidence has gradually risen across the globe. According to relevant studies, NAFLD and the Nrf2 signaling pathway are tightly connected. Inhibiting lipid production and metabolism-related enzymes, repairing impaired liver metabolism, and lowering hepatic lipid storage are all possible with Nrf2 activation. Exercise is a powerful tool for treating and preventing NAFLD. However, exercise type, exercise intensity, environment, and exhaustion all have an impact on the Nrf2 signaling pathway. By activating Nrf2, exercise can lessen liver inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance, and ameliorate liver damage to improve NAFLD. The activation of Nrf2 signaling pathway, its associated mechanism of controlling antioxidation, and the impact of exercise on the Nrf2 signaling pathway are all explained in this work. Based on the pathogenesis of NAFLD, this article examines the connection between exercise, Nrf2, and NAFLD, and the current state of knowledge regarding Nrf2’s role in the amelioration of NAFLD through exercise. It offers a theoretical frame of reference for future research into how Nrf2 might be used to improve NAFLD.
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RATIONALE: This is the first reported severe thallium poisoning patient successfully treated with Prussian blue (PB) and plasma exchange (PE). PATIENT CONCERNS: A 42-year-old woman in a coma owing to severe thallium poisoning was admitted to our department after day 44 of poisoning. At admission, blood and urine thallium concentrations were 380.0 and 2580.0âng/mL, respectively. DIAGNOSIS: The patient was diagnosed with toxic encephalopathy induced by thallium poisoning; in addition, she was also diagnosed with bilateral pneumonia, respiratory failure, moderate anemia, hypoproteinemia, and electrolyte imbalance based on her chest X-ray, blood gas analysis, Hb level, albumin levels, and serum electrolyte results. INTERVENTIONS: The patient was intubated and treated with PB (6600âmg/d, 15 days in total) combined with PE (once daily, 5 days in total) as well as other symptomatic supportive care measures. OUTCOMES: After treatments, her blood and urinary thallium concentrations gradually decreased and on the 13th day after admission, the blood thallium concentration decreased to 0âng/mL. The oxygenation index gradually improved, meantime, the patient gradually regained consciousness, and on the 50th day of admission, the patient's consciousness reverted to a clear-headed state. The patient recovered mostly after 37 months of follow-up. LESSONS: Through this case, we learned that the gradual reduction in blood and urine thallium concentration and the patient's improved condition is correlated with PB and PE treatment. For patients with severe thallium poisoning, this treatment method might be effective; but the exact curative effect is unconfirmed, requiring further research to verify.
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Coma/terapia , Ferrocianuros/uso terapéutico , Síndromes de Neurotoxicidad/diagnóstico , Intercambio Plasmático/métodos , Talio/envenenamiento , Adulto , Coma/inducido químicamente , Femenino , Humanos , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/terapia , Talio/sangre , Talio/orinaRESUMEN
Programmed death ligand-1 (PD-L1) is an important immune checkpoint for cancer immunotherapy in clinic. In this study, we reported that platycodin D, a natural product isolated from an edible and medicinal plant Platycodon grandiflorus (Jacq.) A. DC., down-regulated the protein level of PD-L1 in lung cancer cells. Flow cytometry and immunofluorescence assay showed a weaker surface PD-L1 signal in NCI-H1975â¯cells after the incubation with platycodin D (10⯵M) for 15â¯min compared to the control group. Jurkat T cells showed enhancive interleukin-2 secretion when co-cultured with platycodin D-treated NCI-H1975â¯cells, suggesting that platycodin D-induced PD-L1 reduction increases the activation of Jurkat T cells. An augmentation of PD-L1 protein was detected in the cell culture medium from platycodin D treatment group. Chlorpromazine (60⯵M) almost abolished the platycodin D-mediated PD-L1 extracellular release and restored the membrane PD-L1. Finally, hemolysis assay exhibited that platycodin D-triggered PD-L1 extracellular release was independent of the hemolytic mechanism. Taken together, our study demonstrates that platycodin D reduces the protein level of PD-L1 in lung cancer cells via triggering its release into the cell culture medium, which sheds new light for the application of natural products in cancer immunotherapy.
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Antígeno B7-H1/metabolismo , Saponinas/farmacología , Triterpenos/farmacología , Línea Celular Tumoral , Clorpromazina/farmacología , Humanos , Interleucina-2/metabolismo , Células Jurkat , Transporte de Proteínas/efectos de los fármacosRESUMEN
Thallium is highly toxic and its effects are cumulative. The clinical symptoms of thallium poisoning are non-specific, thereby delaying admission and treatment. This study aimed to summarize the clinical features and treatment experience of patients with delayed admission who experience thallium poisoning.We conducted a retrospective descriptive analysis of patients in our hospital from 2008 to 2018 who had thallium poisoning and experienced a delay in hospital admission. The time from symptom onset to admission was assessed. The patients were divided into 3 groups and descriptive analyses of their clinical characteristics, including basic patient information, symptoms, laboratory test results, examination findings, treatment methods, outcomes, and follow-up information, were conducted.A total of 34 patients with thallium poisoning were included: 8 were admitted to the hospital early or with mild delay, 9 had a moderate delay, and 17 had a severely delayed admission. The time from illness onset to admission was 13 (interquartile range, 7.5-26) days. Some patients with delayed admission had significant symptoms associated with central nervous system damage, and changes in magnetic resonance images and electroencephalograms were also noted. After admission, all patients received Prussian blue treatment, and some patients with relatively high blood concentration received blood purification treatments. Following treatment, the blood and urine thallium concentrations of all patients decreased significantly, and their symptoms were alleviated.Our results show that delayed patient admission in cases of thallium poisoning is associated with greater risk of central nervous system damage. Use of Prussian blue combined with blood purification treatments might improve patients' conditions.
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Diagnóstico Tardío , Intoxicación por Metales Pesados/diagnóstico , Intoxicación por Metales Pesados/terapia , Hospitalización , Talio/envenenamiento , Tiempo de Tratamiento , Adolescente , Adulto , Antídotos/uso terapéutico , Femenino , Ferrocianuros/uso terapéutico , Intoxicación por Metales Pesados/sangre , Intoxicación por Metales Pesados/orina , Hemoperfusión , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Talio/sangre , Talio/orinaRESUMEN
With Zang-Fu organs, meridians, Qi and blood, and body fluid as the physiological and pathological basis, traditional Chinese medicine(TCM) theory is guided by the holistic concept and characterized by syndrome differentiation. It has made significant contributions to human health maintenance and disease prevention. Modern TCM preparation is developed on the basis of inheriting and developing TCM preparations using modern science and technology under the guidance of TCM theory. At present, the incidence and mortality of common tumors are increasing. TCM has rich clinical experience in the treatment of tumors. However, in the current stage, some TCM preparations have a tendency to deviate from the guidance of TCM theory. With the modernization of TCM, it is worth considering how TCM theory guides modern TCM preparations. Taking tumor treatment as an example, this paper introduced the development of TCM nano-preparation under the influence of modern nanotechnology, summarized the research on the development of modern TCM nano-preparation from the aspects of TCM holistic concept, TCM treatment principles, and TCM theory application, and discussed the application prospect of TCM nano-preparation in overall therapy, drug pairing, carrier selection, and targeted substance selection under the guidance of TCM theory. This paper provides new references for further developing the combination of tradition and modernization of TCM nano-preparation.
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Humanos , Medicina Tradicional China , Medicamentos Herbarios Chinos/uso terapéutico , Productos Biológicos , Nanotecnología , Neoplasias/tratamiento farmacológicoRESUMEN
Objective:To summarize the clinical characteristics of neonatal brain abscess and improve the understanding of diagnosis and treatment of this disease.Methods:Clinical data of five cases of neonatal brain abscess admitted to the First Affiliated Hospital of Zhengzhou University from December 2018 to March 2021 were retrospectively analyzed and followed-up.Results:Among five cases, four cases were premature and one was term infant, three were girls and two were boys. The age of onset was 10, 5, 2, 28 and 11 days after birth, and all had fever as the first manifestation. Three cases had positive blood or cerebrospinal fluid cultures, and the diagnosis of brain abscess was confirmed by head imaging, with the most common lesion being in the frontal lobe. One case was treated conservatively, and four cases underwent abscess aspiration and drainage. After treatment, the range of lesions in five cases was reduced and the clinical symptoms were improved. The neurodevelopmental assessment after discharge did not reveal any intelligence or motor retardation in three cases, and were developing as the same age, while the other two cases had various degrees of neurological sequelae.Conclusion:The clinical characteristics of neonatal brain abscess are not specific, so it is necessary to conduct head imaging examination as early as possible for neonates with septicemia and meningitis with poor therapeutic effect or recurrent disease, so as to improve the early diagnosis rate and long-term prognosis.