Enhancing prognostic prediction of invasive candidiasis among cancer patients with a serum C5a-based scoring model.

PURPOSE: Invasive candidiasis poses a life-threatening risk, and early prognosis assessment is vital for timely interventions to reduce mortality. Serum C5a levels have recently been linked to prognosis, but confirmation in cancer patients is pending. METHODS: We detected the concentrations of serum C5a in hospitalized cancer patients with invasive candidiasis from 2020 to 2023, and retrospectively analyzed the clinical data. RESULTS: 372 cases were included in this study, with a 90-day mortality rate of 21.8%. Candida albicans (48.7%) remained the predominant pathogen, followed by Candida glabrata (25.5%), Candida tropicalis (12.4%), and Candida parapsilosis (8.3%). Gastrointestinal cancer was the most diagnosed pathology type (37.6%). Serum C5a demonstrated a noteworthy correlation with 90-day mortality, and employing a cutoff value of 36.7 ng/ml revealed significantly higher 90-day mortality in low-C5a patients (41.2%) compared to high-C5a patients (6.3%) (p < 0.001). We also identified no source control, no surgery, metastasis, or chronic renal failure independently correlated with the 90-day mortality. Based on this, a prognostic model combining C5a and clinical parameters was constructed, which performed better than models built solely on C5a or clinical parameters. Furthermore, we weighted scores to each parameter in the model and presented diagnostic sensitivity and specificity corresponding to different score points calculated by the model. CONCLUSION: We constructed a prognostic scoring model including serum C5a and clinical parameters, which would contribute to precise prognosis assessment and benefit the outcome among cancer patients.

Trace amounts of palladium catalysed the Suzuki-Miyaura reaction of deactivated and hindered aryl chlorides.

Electron-rich and hindered aryl chlorides are the most challenging substrates in Suzuki-Miyaura cross-coupling (SMC) reactions. Herein, we report a highly efficient catalytic system for the SMC reaction using trace amounts of commercially available catalysts [Pd(PPh3)4/(t-Bu)PCy2; Pd loading as low as 9.5 × 10-5 mol%]. This catalytic system can efficiently couple deactivated and sterically hindered aryl chlorides with various substituted phenylboronic acids, even in one-pot multiple coupling reactions (yield of products up to 92%). The impact of solvents on SMC reactions and the mechanisms of by-product formation in aryl boronic acid couplings are analyzed using density functional theory (DFT). Utilizing trace amounts of commercially available catalysts avoids complex synthesis, reduces costs, and minimizes metal residues.

Effect of vitamin D on pregnancy in women with polycystic ovary syndrome: retrospective and prospective studies.

RESEARCH QUESTION: Does vitamin D affect the pregnancy rate of patients with polycystic ovary syndrome (PCOS) receiving ovulation-induction therapy? DESIGN: The retrospective study included 200 patients with PCOS and 200 healthy women. The prospective study included 160 patients with PCOS receiving vitamin D or placebo supplementation. Pregnancy rates were assessed after a maximum of three cycles of ovulation induction. Serum concentrations of 25-hydroxycalciferol [25-(OH)D3], LH, FSH, progesterone, oestradiol, testosterone and fasting insulin; LH/FSH ratio; and body mass index were evaluated. RESULTS: In the retrospective study, patients with PCOS had lower 25-(OH)D3 concentrations than healthy women, pregnant patients with PCOS had higher 25-(OH)D3 concentrations than non-pregnant patients with PCOS (both P = 0.000), and the pregnancy rate was lower in the vitamin-D-deficient group compared with the non-vitamin-D-deficient group (P = 0.022). In the prospective study, compared with placebo supplementation, vitamin D supplementation increased the serum concentration of 25-(OH)D3 (P = 0.000), and reduced the LH/FSH ratio, and concentrations of LH and testosterone significantly (all P ≤ 0.049). After the intervention, it was found that the LH/FSH ratio, and concentrations of LH and testosterone were significantly lower in both groups compared with pre-intervention (P = 0.000). After ovulation induction, the pregnancy rate was higher in patients in the vitamin D supplementation group compared with the placebo supplementation group (P = 0.049). CONCLUSIONS: Vitamin D deficiency is common in patients with PCOS, and vitamin-D-deficient patients with PCOS have lower pregnancy rates after ovulation induction compared with non-vitamin-D-deficient patients with PCOS. Vitamin D supplementation can improve the pregnancy rate and mitigate basic hormone disorders. Therefore, monitoring vitamin D supplementation and checking vitamin D concentrations before and during interventions are essential for patients with PCOS.

Case report: A case of hyperthyroidism secondary to bone metastasis of differentiated thyroid cancer.

It is usually believed that differentiated thyroid cancer is less likely to have distant metastases and rarely occurs secondary to hyperthyroidism. In our case report, we describe a patient diagnosed with thyroid fetal adenoma in 2002 who subsequently presented with a painful lump in her right rib. Through puncture biopsy, the mass was considered as metastatic follicular thyroid carcinoma, and then she appeared to have hyperthyroidism. The results of SPECT examination and other tests suggested that the hyperthyroidism was secondary to the thyroid cancer. The patient further underwent total thyroidectomy, and the pathology did not find any follicular thyroid foci. In this article, we analyze and discuss this case and review the relevant literature.

Application of micro/nanorobot in medicine.

The development of micro/nanorobots and their application in medical treatment holds the promise of revolutionizing disease diagnosis and treatment. In comparison to conventional diagnostic and treatment methods, micro/nanorobots exhibit immense potential due to their small size and the ability to penetrate deep tissues. However, the transition of this technology from the laboratory to clinical applications presents significant challenges. This paper provides a comprehensive review of the research progress in micro/nanorobotics, encompassing biosensors, diagnostics, targeted drug delivery, and minimally invasive surgery. It also addresses the key issues and challenges facing this technology. The fusion of micro/nanorobots with medical treatments is poised to have a profound impact on the future of medicine.

Controlling the Collective Behaviors of Ultrasound-Driven Nanomotors via Frequency Regulation.

Controlling the collective behavior of micro/nanomotors with ultrasound may enable new functionality in robotics, medicine, and other engineering disciplines. Currently, various collective behaviors of nanomotors, such as assembly, reconfiguration, and disassembly, have been explored by using acoustic fields with a fixed frequency, while regulating their collective behaviors by varying the ultrasound frequency still remains challenging. In this work, we designed an ultrasound manipulation methodology that allows nanomotors to exhibit different collective behaviors by regulating the applied ultrasound frequency. The experimental results and FEM simulations demonstrate that the secondary ultrasonic waves produced from the edge of the sample cell lead to the formation of complex acoustic pressure fields and microfluidic patterns, which causes these collective behaviors. This work has important implications for the design of artificial actuated nanomotors and optimize their performances.

A novel model for predicting deep-seated candidiasis due to Candida glabrata among cancer patients: A 6-year study in a cancer center of China.

Followed by Candida albicans, Candida glabrata ranks as the second major species contributing to invasive candidiasis. Given the higher medical burden and lower susceptibility to azoles in C. glabrata infections, identifying these infections is critical. From 2016 to 2021, patients with deep-seated candidiasis due to C. glabrata and non-glabrata Candida met the criteria to be enrolled in the study. Clinical data were randomly divided into training and validation cohorts. A predictive model and nomogram were constructed using R software based on the stepwise algorithm and logistic regression. The performance of the model was assessed by the area under the receiver operating characteristic curve and decision curve analysis (DCA). A total of 197 patients were included in the study, 134 of them infected with non-glabrata Candida and 63 with C. glabrata. The predictive model for C. glabrata infection consisted of gastrointestinal cancer, co-infected with bacteria, diabetes mellitus, and kidney dysfunction. The specificity was 84.1% and the sensitivity was 61.5% in the validation cohort when the cutoff value was set to the same as the training cohort. Based on the model, treatment for patients with a high-risk threshold was better than 'treatment for all' in DCA, while opting low-risk patients out of treatment was also better than 'treatment for none' in opt-out DCA. The predictive model provides a rapid method for judging the probability of infections due to C. glabrata and will be of benefit to clinicians making decisions about therapy strategies.

Carcinogenic Role and Clinical Significance of Histone H3-H4 Chaperone Anti-silencing Function 1 B (ASF1B) in Lung Adenocarcinoma.

Histone H3-H4 chaperone anti-silencing function 1 (ASF1) plays an important role in the polymerization, transport, and modification of histones. However, the significance of ASF1B in lung adenocarcinoma (LUAD) is largely overlooked. We investigated the aberrant expression of ASF1B in LUAD and its potential link to patient survival using multiple databases. ASF1B-overexpressing and knockdown cell lines were constructed to explore its effects on the biological behavior of lung cancer cells. ssGSEA, TMB, TIDE and IMvigor210 cohort were used to explore and validate the association of ASF1B to tumor immunity. Our data suggested that ASF1B was overexpressed in LUAD, and was associated with poor prognosis. ASF1B promoted the proliferation, migration, and invasion of lung cancer cells by regulating the phosphorylation of AKT in vitro. ASF1B was associated with tumor immunity. In summary, ASF1B may promote malignant behavior of LUAD cells, and its overexpression correlates with worse prognosis and better immunotherapy effect.

Accurately predicting the risk of unfavorable outcomes after endovascular coil therapy in patients with aneurysmal subarachnoid hemorrhage: an interpretable machine learning model.

BACKGROUND: Despite endovascular coiling as a valid modality in treatment of aneurysmal subarachnoid hemorrhage (aSAH), there is a risk of poor prognosis. However, the clinical utility of previously proposed early prediction tools remains limited. We aimed to develop a clinically generalizable machine learning (ML) models for accurately predicting unfavorable outcomes in aSAH patients after endovascular coiling. METHODS: Functional outcomes at 6 months after endovascular coiling were assessed via the modified Rankin Scale (mRS) and unfavorable outcomes were defined as mRS 3-6. Five ML algorithms (logistic regression, random forest, support vector machine, deep neural network, and extreme gradient boosting) were used for model development. The area under precision-recall curve (AUPRC) and receiver operating characteristic curve (AUROC) was used as main indices of model evaluation. SHapley Additive exPlanations (SHAP) method was applied to interpret the best-performing ML model. RESULTS: A total of 371 patients were eventually included into this study, and 85.4% of them had favorable outcomes. Among the five models, the DNN model had a better performance with AUPRC of 0.645 (AUROC of 0.905). Postoperative GCS score, size of aneurysm, and age were the top three powerful predictors. The further analysis of five random cases presented the good interpretability of the DNN model. CONCLUSION: Interpretable clinical prediction models based on different ML algorithms have been successfully constructed and validated, which would serve as reliable tools in optimizing the treatment decision-making of aSAH. Our DNN model had better performance to predict the unfavorable outcomes at 6 months in aSAH patients compared with Yan's nomogram model.

A multicenter prospective study of lateral neck lymph node mapping in papillary thyroid cancer.

Background: Despite the high incidence of lateral neck lymph node (LN) metastasis in papillary thyroid cancer (PTC), the management of the lateral neck remains controversial. We aimed to map the draining LNs in the lateral neck using carbon nanoparticles and explore its potential in neck evaluation. Methods: We conducted a multicenter, prospective study in PTC patients who had non-palpable yet suspicious metastatic lateral LNs on ultrasound and/or computed tomography (CT) but could not be confirmed by fine needle aspiration. Carbon nanoparticle suspension was injected peritumorally into the thyroid and modified lateral neck dissection was subsequently performed. Results: A total of 154 patients were enrolled for analysis. And 5,070 lateral LNs were removed, of which 1,079 (21.3%) were dyed. The median of dyed LNs was 6 per case (range, 1-33). The distribution of dyed LNs in neck compartments was IV > III > IIA > IIB/V, independent of tumor size, location, multifocality or microscopic extra-thyroidal extension (ETE). Compared with undyed LNs, the probabilities of metastasis in dyed LNs were significantly increased in compartment III, IV, V, and II-V (III: 29.3% vs. 15.4%, P<0.001; IV: 26.3% vs. 14.5%, P<0.001; V: 16.7% vs. 3.3%, P=0.005; II-V: 26.3% vs. 10.0%, P<0.001). The relative risks of metastasis in dyed LNs compared with undyed LNs were 1.90, 1.82, 5.04 and 2.62 in compartment III, IV, V, and II-V, respectively. Conclusions: It was the first prospective multicenter study to map the lateral neck LNs with carbon nanoparticles, which could help surgeons visualize the suspicious LNs during surgery. Instead of unguided LN biopsy, this method has a potential role in lateral neck assessment for indeterminate lateral LNs in PTC.

Dynamic and visual nomograms to online predict unfavorable outcome of mechanical thrombectomy for acute basilar artery occlusion.

BACKGROUND: The evidence of mechanical thrombectomy (MT) in basilar artery occlusion (BAO) was limited. This study aimed to develop dynamic and visual nomogram models to predict the unfavorable outcome of MT in BAO online. METHODS: BAO patients treated with MT were screened. Preoperative and postoperative nomogram models were developed based on clinical parameters and imaging features. An independent dataset was collected to perform external validation. Web-based calculators were constructed to provide convenient access. RESULTS: A total of 127 patients were included in the study, and 117 of them were eventually included in the analysis. The nomogram models showed robust discrimination, with an area under the receiver operating characteristic (ROC) of 0.841 (preoperative) and 0.916 (postoperative). The calibration curves showed good agreement. The preoperative predictors of an unfavorable outcome were previous stroke, the National Institutes of Health Stroke Scale (NIHSS) at admission, and the posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS). The postoperative predictors were previous stroke, NIHSS at 24 h, and pc-ASPECTS. CONCLUSION: Dynamic and visual nomograms were constructed and validated for the first time for BAO patients treated with MT, which provided precise predictions for the risk of an unfavorable outcome. The preoperative model may assist clinicians in selecting eligible patients, and the postoperative model may facilitate individualized poststroke management.

Case report: Extrapontine myelinolysis combined with flupentixol- and melitracen-induced dysphagia.

Extrapontine myelinolysis (EPM) is a rare symmetrical demyelinating disease of the central nervous system, which is often accompanied with central pontine myelinolysis (CPM) or can appear alone. A combination of flupentixol and melitracen is used as an antianxiety-antidepressant drug which may induce hyponatremia. Herein, we report a 46-year-old woman with depression who was treated with flupentixol and melitracen 0.5/10 mg once daily for 6 months. Later, the dosage increased to 0.5/10 mg twice daily. At the same time, she had complains of intermittent dizziness and fatigue. The laboratory test revealed hyponatremia (121 mmol/L). Dizziness was improved after sodium supplementation, with an increase in blood sodium to 133 mmol/L. Twenty days later, she had difficulty opening the mouth and swallowing, needing a gastric tube due to severe dysphagia. Head magnetic resonance imaging (MRI) showed a symmetric abnormal signal of caudate nucleus and lenticular nuclei. The symptoms were not relieved after active treatment, such as rehydration. However, her symptoms improved significantly after discontinuation of flupentixol and melitracen and switching to promethazine. Follow-up head MRI after 4 months revealed no abnormal signals. The patient who developed EPM had dysphagia, despite appropriate correction of hyponatremia. Flupentixol and melitracen can cause hyponatremia and dysphagia. This case highlights an unexpected association between EPM and flupentixol- and melitracen-induced dysphagia.

Autophagy and LC3-associated phagocytosis contribute negatively to the killing capability of THP-1-derived macrophages against Candida albicans at the mid-stage.

In innate immunity, macrophages play critical roles in defending against pathogens via the lysosomal degradation function of autophagy. Two distinct autophagy pathways have been identified in decades: canonical autophagy (referred to as autophagy) and LC3-associated phagocytosis (LAP). Since several conflicting findings about the anti-Candida capability of autophagy (or LAP) have been reported, they serve as the foe or friend for Candida survival is still unclearly. The current study showed that the fungicidal process of THP-1-derived macrophages (THP-1-MФ) against Candida albicans is divided into three stages as follows, the early stage (the first 12 h, increasing in the killing capability), the mid-stage (12-24 h, no change in killing capability), and the late stage (24-48 h, decreasing of the killing capability). Autophagic protein LC3B-II reached the peak in THP-1-MФ after 24 h inoculated either with C.albicans or whole glucan particles (WGP). Thus, both anti-Candida roles of autophagy and the LAP pathway have been detected at the mid-stage. For autophagy, after 24 h inoculation with C.albicans, ULK1 increased, but p-ATG13(s318) decreased obviously in THP-1-MФ, and the killing assay showed that autophagy is unhelpful for Candida killing capability. For the LAP pathway, Rubicon and ROS raised significantly in THP-1-MФ after 24 h inoculated with C.albicans; each inhibition would sharply cut down the LC3B-II accumulation, which indicated that LAP had been induced. However, mCherry-GFP-LC3 fluorescent assay exhibited that LAP phago-lysosomal fusion has been blocked, and Rubicon knockdown facilitated the Candida killing activity. These data indicated that autophagy presented as redundant to Candida defense, and LAP phago-lysosomal fusion obstruction impairs the Candida killing capability of THP-1-MФ at the mid-stage. That may explain the no change in Candida killing capability at the mid-stage.

Association of dietary fatty acid intake with hypertension in children and adolescents: evidence from the NHANES 2005-2018.

Aim: This study aims to evaluate the association between dietary fatty acid intake and hypertension in children and adolescents. Methods: This cross-sectional study used data of children and adolescents aged 8-17 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Dietary intake of total fat and fatty acid was evaluated via two 24-h dietary recall interviews. Multivariate logistic regression models were used to assess the association between fatty acid intake and hypertension, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. A subgroup analysis was conducted according to gender, age, and body mass index Z-score. Results: This study included 13,330 subjects, of which 11,614 were non-hypertensive and 1,716 were hypertensive. Higher intake of total polyunsaturated fatty acids (PUFAs) was associated with significantly lower odds of hypertension (OR = 0.85, 95% CI: 0.74-0.97, P = 0.018). No significant associations were found between the density of total saturated fatty acid, monounsaturated fatty acids, and PUFAs and the odds of hypertension (all P > 0.05). Increased intake of omega-3 (OR = 0.82, 95% CI: 0.72-0.93, P = 0.002) and omega-6 (OR = 0.86, 95% CI: 0.75-0.98, P = 0.025) PUFAs, octadecatrienoic acid (OR = 0.82, 95% CI: 0.72-0.93, P = 0.003), and octadecadienoic acid (OR = 0.86, 95% CI: 0.75-0.98, P = 0.025) was associated with significantly lower odds of hypertension, and individuals with higher omega-6/omega-3 ratio had significantly higher odds of hypertension (OR = 1.09, 95% CI: 1.02-1.17, P = 0.025). The density of omega-3 PUFAs (OR = 0.86, 95% CI: 0.78-0.95, P = 0.004) and octadecatrienoic acid (OR = 0.87, 95% CI: 0.78-0.96, P = 0.006) was inversely associated with the odds of hypertension, and the omega-6/omega-3 ratio was positively associated with the odds of hypertension (OR = 1.09, 95% CI: 1.02-1.17, P = 0.012). Conclusion: Total PUFA intake was negatively associated with the odds of hypertension in children and adolescents. Higher intake of omega-3 and omega-6 PUFAs, octadecatrienoic acid, and octadecadienoic acid, as well as density of omega-3 PUFAs and octadecatrienoic acid, was associated with lower odds of hypertension.

Pre- and Post-Operative Online Prediction of Outcome in Patients Undergoing Endovascular Coiling after Aneurysmal Subarachnoid Hemorrhage: Visual and Dynamic Nomograms.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) causes long-term functional dependence and death. Early prediction of functional outcomes in aSAH patients with appropriate intervention strategies could lower the risk of poor prognosis. Therefore, we aimed to develop pre- and post-operative dynamic visualization nomograms to predict the 1-year functional outcomes of aSAH patients undergoing coil embolization. METHODS: Data were obtained from 400 aSAH patients undergoing endovascular coiling admitted to the People's Hospital of Hunan Province in China (2015-2019). The key indicator was the modified Rankin Score (mRS), with 3-6 representing poor functional outcomes. Multivariate logistic regression (MLR)-based visual nomograms were developed to analyze baseline characteristics and post-operative complications. The evaluation of nomogram performance included discrimination (measured by C statistic), calibration (measured by the Hosmer-Lemeshow test and calibration curves), and clinical usefulness (measured by decision curve analysis). RESULTS: Fifty-nine aSAH patients (14.8%) had poor outcomes. Both nomograms showed good discrimination, and the post-operative nomogram demonstrated superior discrimination to the pre-operative nomogram with a C statistic of 0.895 (95% CI: 0.844-0.945) vs. 0.801 (95% CI: 0.733-0.870). Each was well calibrated with a Hosmer-Lemeshow p-value of 0.498 vs. 0.276. Moreover, decision curve analysis showed that both nomograms were clinically useful, and the post-operative nomogram generated more net benefit than the pre-operative nomogram. Web-based online calculators have been developed to greatly improve the efficiency of clinical applications. CONCLUSIONS: Pre- and post-operative dynamic nomograms could support pre-operative treatment decisions and post-operative management in aSAH patients, respectively. Moreover, this study indicates that integrating post-operative variables into the nomogram enhanced prediction accuracy for the poor outcome of aSAH patients.

The predictive role of soluble programmed death ligand 1 in digestive system cancers.

Introduction: The prognostic role of soluble programmed death ligand 1 (sPD-L1) in digestive system cancers (DSCs) remains inconclusive. This study aimed to explore the predictive value of sPD-L1 expression in DSCs. Methods: Comprehensive searches were run on the electronic databases (PubMed, Web of Science, EMBASE, and the Cochrane Library) to identify studies that assessed the prognostic role of sPD-L1 in DSCs. Review Manager software (version 5.3) was used for all analyses. Pooled data for survival outcomes were measured as hazard ratios (HRs), 95% confidence intervals (CIs), and odds ratios and their 95% CIs. Results: The search identified 18 studies involving 2,070 patients with DSCs. The meta-outcome revealed that a high level of sPD-L1 was related to poorer overall survival (HR, 3.06; 95% CI: 2.22-4.22, p<0.001) and disease-free survival (HR, 2.53; 95% CI: 1.67-3.83, p<0.001) in DSCs. Individually, the prognostic significance of high level of sPD-L1 expression was the highest in hepatic cell carcinoma (HR, 4.76; p<0.001) followed by gastric cancer (HR=3.55, p<0.001). Conclusion: sPD-L1 may be a prognostic factor in DSCs for overall survival and disease-free survival. Inflammatory cytokines, treatment approaches, and other factors may affect the expression of sPD-L1. Therefore, the prognostic value of sPD-L1 for recurrence and metastasis should be further investigated. sPD-L1 may also predict response to treatment. Well-designed prospective studies with standard assessment methods should be conducted to determine the prognostic value of sPD-L1 in DSCs.

The Hepatic Nerves Regulated Inflammatory Effect in the Process of Liver Injury: Is Nerve the Key Treating Target for Liver Inflammation?

Liver injury is a common pathological basis for various liver diseases. Chronic liver injury is often an important initiating factor in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, hepatitis A and E infections are the most common causes of acute liver injury worldwide, whereas drug toxicity (paracetamol overdose) in the USA and part of Western Europe. In recent years, chronic liver injury has become a common disease that harms human health. Meanwhile, the main causes of chronic liver injury are viral hepatitis (B, C) and long-term alcohol consumption worldwide. During the process of liver injury, massive inflammatory cytokines are stimulated by these hazardous factors, leading to a systemic inflammatory response syndrome, followed by a compensatory anti-inflammatory response, which causes immune cell dysfunction and sepsis, subsequent multi-organ failure. Cytokine release and immune cell infiltration-mediated aseptic inflammation are the most important features of the pathobiology of liver failure. From this perspective, diminishing the onset and progression of liver inflammation is of clinical importance in the treatment of liver injury. Although many studies have hinted at the critical role of nerves in regulating inflammation, there largely remains undetermined how hepatic nerves mediate immune inflammation and how the inflammatory factors released by these nerves are involved in the process of liver injury. Therefore, the purpose of this article is to summarize previous studies in the field related to hepatic nerve and inflammation as well as future perspectives on the aforementioned questions. Our findings were presented in three aspects: types of nerve distribution in the liver, how these nerves regulate immunity, and the role of liver nerves in hepatitis and liver failure.

Targeting Pokemon is a novel strategy to suppress cancer aggressiveness of non-small cell lung cancer: Identification of Pokemon as ideal target for developing anti-NSCLC drugs.

Although it is widely reported that Pokemon acts as an oncogene in the pathogenesis of multiple cancers, but its role and detailed molecular mechanisms in regulating non-small cell lung cancer (NSCLC) progression have not been fully delineated. Here, by performing Real-Time qPCR analysis, we verified that Pokemon was high-expressed in NSCLC tissues and cells, compared to the corresponding normal lung tissues and epithelial cells. Then, the small interfering RNA (siRNA) for Pokemon was transfected into the NSCLC cells to verify its biological functions, and our results suggested that silencing of Pokemon suppressed the malignant phenotypes, including cell viability, mitosis, colony formation, epithelial-mesenchymal transition (EMT), mobility and cancer stem cell (CSC) properties in NSCLC cells. Mechanistically, we confirmed that knockdown of Pokemon decreased the expression levels of phosphorylated Akt (p-Akt), phosphorylated GSK-3ß (p-GSK-3ß) and Snail to inactivate the oncogenic Akt/GSK-3ß/Snail signal pathway, and deletion of Snail also had similar effects to hamper the development of NSCLC. Next, our rescuing experiments validated that Pokemon ablation-induced suppressing effects on NSCLC cell malignancy were all abrogated by overexpressing Snail. Finally, the in vivo experiments confirmed that silencing of Pokemon downregulated Snail to hamper tumorigenesis of NSCLC cells in xenograft tumor-bearing mice models. Taken together, we firstly uncovered the underlying mechanisms by which the Pokemon/Akt/GSK-3ß/Snail signal pathway contributed to the development of NSCLC, and this signal pathway could be potentially used as therapeutic targets for the development of personalized anti-NSCLC drugs.

In vivo anti-hepatitis B activity of Artemisia argyi essential oil-loaded nanostructured lipid carriers. Study of its mechanism of action by network pharmacology and molecular docking.

BACKGROUND: Hepatitis B virus (HBV) infection remains a major global health burden, due to the increasing risk of complications, such as cirrhosis and hepatocellular carcinoma. Novel anti-HBV agents are critical required. Our previous study suggested that Artemisia argyi essential oil (AAEO) significantly inhibited the replication of HBV DNA and especially the secretion of hepatitis B antigen in vitro. PURPOSE: The aim of this study was to prepare AAEO loaded nanostructured lipid carriers (AAEO-NLCs) for the delivery of AAEO to the liver, investigated the therapeutic benefits of AAEO-NLCs against HBV in a duck HBV (DHBV) model and explored its potential mechanism. STUDY DESIGN AND METHODS: AAEO-NLCs were prepared by hot homogenization and ultrasonication method. The DHBV-infected ducks were treated with AAEO (4 mg/kg), AAEO-NLCs (0.8, 4, and 20 mg/kg of AAEO), and lamivudine (20 mg/kg) for 15 days. The DHBV DNA levels in the serum and liver were measured by quantitative Real-Time PCR. Pharmacokinetics and liver distribution were performed in rats after oral administration of AAEO-NLCs and AAEO suspension. The potential antiviral mechanism and active compounds of AAEO were investigated by network pharmacology and molecular docking. RESULTS: AAEO-NLCs markedly inhibited the replication of DHBV DNA in a dose-dependent manner and displayed a low virologic rebound following withdrawal the treatment in DHBV-infected ducks. Moreover, AAEO-NLCs led to a more pronounced reduction in viral DNA levels than AAEO suspension. Further investigations of pharmacokinetics and liver distribution in rats confirmed that NLCs improved the oral bioavailability and increased the liver exposure of AAEO. The potential mechanisms of AAEO against HBV explored by network pharmacology were associated with signaling pathways related to immune response, such as tumor necrosis factor, nuclear factor kappa B, and sphingolipid signaling pathways. Furthermore, a total of 16 potential targets were obtained, including prostaglandin-endoperoxide synthase-2 (PTGS2), caspase-3, progesterone receptor, etc. Compound-target docking results confirmed that four active compounds of AAEO had strong binding interactions with the active sites of PTGS2. CONCLUSIONS: AAEO-NLCs displayed potent anti-HBV activity with improved oral bioavailability and liver exposure of AAEO. Thus, it may be a potential therapeutic strategy for the treatment of HBV infection.