Nobiletin enhances the antifungal activity of eugenol nanoemulsion against Penicillium italicum in both in vitro and in vivo settings.

The study prepared and used eugenol nanoemulsion loaded with nobiletin as fungistat to study its antifungal activity and potential mechanism of Penicillium italicum (P. italicum). The results showed that the minimum inhibitory concentration (MIC) of eugenol nanoemulsion loaded with nobiletin (EGN) was lower than that of pure eugenol nanoemulsion (EG), which were 160 µg/mL and 320 µg/mL, respectively. At the same time, the mycelial growth inhibition rate of EGN nanoemulsion (54.68 %) was also higher than that of EG nanoemulsion (9.92 %). This indicates that EGN nanoemulsion is more effective than EG nanoemulsion. Compared with EG nanoemulsion, the treatment of EGN nanoemulsion caused more serious damage to the cell structure of P. italicum. At the same time, in vitro inoculation experiments found that EGN nanoemulsion has better control and delay the growth and reproduction of P. italicum in citrus fruits. And the results reflected that EGN nanoemulsion may be considered as potential resouces of natural antiseptic to inhibit blue mold disease of citrus fruits, because it has good antifungal activity.

Association of serum vitamin C levels with Asthma in adults: results of NHANES 2003-2006 and mendelian randomization study.

BACKGROUND: The protective effect of vitamin C as an antioxidant against asthma in adults remains controversial. This study used an observational study and Mendelian randomization (MR) analysis to investigate the association between adult asthma and serum vitamin C levels. METHODS: Using information from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, we carried out an observational study. A multivariate logistic regression model was employed to examine the connection between adult asthma and serum vitamin C levels. We used the inverse-variance weighted (IVW) method of MR analysis as the primary method to analyze the causal effect of serum vitamin C levels on asthma in adults. RESULTS: A total of 8,504 participants were included in the observational study, including 639 in the asthma group and 7,865 in the non-asthma group. Before sample weighting, serum vitamin C was associated with a reduced risk of asthma in adults (OR = 0.798, 95% CI: 0.673-0.945, P = 0.009). After sample weighting, serum vitamin C was not associated with adult asthma risk (OR = 0.829, 95% CI: 0.660 ~ 1.042, P = 0.104). MR analysis showed no causal relationship between serum vitamin C and adult asthma in either the UK Biobank (OR = 0.957, 95% CI: 0.871 ~ 1.053, P = 0.370) or FinnGen (OR = 0.973, 95% CI: 0.824 ~ 1.149, P = 0.750) cohorts. CONCLUSION: Our study did not support a causal association between serum vitamin C levels and adult asthma risk. The relationship between serum vitamin C and adult asthma requires further research.

Evaluation of Antioxidant Activity and Drug Delivery Potential of Cell-Derived Extracellular Vesicles from Citrus reticulata Blanco cv. 'Dahongpao'.

Plant extracellular vesicles (PEVs) have attracted increasing attention due to their rich composition, good antioxidant and anti-inflammatory activity, and ability to transport drugs. As a common fruit, citrus is an ideal material for extracting PEVs because of the diversity and abundance of bioactive substances in it. In our study, citrus-derived extracellular vesicles (CEVs) were extracted from red mandarin (Citrus reticulata Blanco cv. 'Dahongpao') and it was found that they contain high levels of lipids, proteins, and carbohydrates. The high levels of total phenols and total flavonoids suggest that CEVs have good chemical antioxidant properties. We also demonstrated through cell experiments that CEVs have significant antioxidant and anti-inflammatory effects. Furthermore, we found that CEVs have an encapsulation rate of 71.5 ± 0.19% and a high drug-carrying capacity of 4.96 ± 0.22% and can enhance antioxidant and anti-inflammatory activity when loaded with tangeretin. Our results show that CEVs contain abundant bioactive components, have low toxicity, exhibit good antioxidant and anti-inflammatory properties, and can serve as drug delivery agents. This study has important implications for utilizing citrus materials and developing natural anti-oxidative and anti-inflammatory biomaterials.

Differentiating between tuberculous and non-tuberculous pleural effusions using the pleural fluid ratio of 10× adenosine deaminase/lactate dehydrogenase.

Background: Adenosine deaminase (ADA) is a sensitive marker of tuberculous pleural effusion (TBPE). However, in pleural effusion (PE), the detection of ADA alone cannot be used to determine whether the increase in the ADA level is caused by the rising proportion of macrophages and lymphocytes in the cell components or by the increase in the total cell number. The diagnostic precision of ADA is probably restricted due to the false positive and negative results. Thus, we explored the clinical value of the ratio of PE ADA to lactate dehydrogenase (LDH) in differentiating between TBPE and non-TBPE. Methods: Patients hospitalized with PEs between January 2018 and December 2021 were retrospectively recruited for this study. We analyzed the values of ADA, LDH, and 10× ADA/LDH in the patients with TBPE and non-TBPE. We also determined the sensitivity, specificity, Youden index, and area under the curve for 10× ADA/LDH at different ADA levels and evaluated its diagnostic accuracy. Results: In total, 382 patients with PEs were included in the study. Among whom, 144 were diagnosed with TBPE, this supposes a "pre-test probability" >40%. It is quite high, 134 with malignant PEs, 19 with parapneumonic PEs, 43 with empyema, 24 with transudate PEs, and 18 with other types of PE of a known etiology. The ADA levels were positively correlated with the LDH levels in TBPE. LDH levels usually increase in response to cell damage or cell death. The 10× ADA/LDH level was significantly increased in the TBPE patients. In addition, the 10× ADA/LDH level increased as the ADA level increased in TBPE. To differentiate between TBPE and non-TBPE, the optimal cut-off value of 10× ADA/LDH at different ADA levels was assessed using receiver operating curves. At an ADA level >20 U/L, 10× ADA/LDH showed the best diagnostic performance, and had a specificity and sensitivity of 0.94 (95% CI: 0.84-0.98) and 0.95 (95% CI: 0.88-0.98), respectively. Conclusions: The 10× ADA/LDH dependent diagnostic index can be used to distinguish TBPE from non-TBPE and could be used to guide future clinical decisions.

BRCA2 mutation in advanced lung squamous cell carcinoma treated with Olaparib and a PD-1 inhibitor: a case report.

Background: Mutations in the human breast cancer susceptibility gene 2 (breast cancer 2, BRCA2) increase the risk of breast, ovarian and other cancers. Olaparib, an oral poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP) inhibitor, is usually prescribed to treat BRCA mutated tumors, especially breast and ovarian cancers. Programmed cell death-1 (PD-1) inhibitors have revolutionized the treatment of lung cancer and many other cancers by destroying the interaction between receptors with ligands in the tumor-immune microenvironment and enabling T cells to recognize and attack cancer cells. Case description: In our study, we report a patient with advanced BRCA2 lung squamous cell carcinoma who received platinum-based chemotherapy combined with paclitaxel. Seven months later, the disease progressed. BRCA2 mutations were detected in peripheral blood by next-generation sequencing. After 2 months of treatment with Olaparib combined with Cindilimab, the patient was in partial remission and the progression-free survival (PFS) lasted for 6 months, but the patient developed immune renal damage. Conclusions: This study adds to the clinical data for the treatment of BRCA2 mutant non-small cell lung cancer by demonstrating that lung squamous cell carcinoma has a good response to PARP inhibitors. It also serves as a reminder that there may still be some negative effects from targeted superimposed immunotherapy.

CA916798 predicts poor prognosis and promotes Gefitinib resistance for lung adenocarcinoma.

BACKGROUND: Our previous studies have identified CA916798 as a chemotherapy resistance-associated gene in lung cancer. However, the histopathological relevance and biological function of CA916798 in lung adenocarcinoma (LUAD) remains to be delineated. In this study, we further investigated and explored the clinical and biological significance of CA916798 in LUAD. METHODS: The relationship between CA916798 and clinical features of LUAD was analyzed by tissue array and online database. CCK8 and flow cytometry were used to measure cell proliferation and cell cycle of LUAD after knockdown of CA916798 gene. qRT-PCR and western blotting were used to detect the changes of cell cycle-related genes after knockdown or overexpression of CA916798. The tumorigenesis of LUAD cells was evaluated with or without engineering manipulation of CA916798 gene expression. Response to Gefitinib was evaluated using LUAD cells with forced expression or knockdown of CA916798. RESULTS: The analysis on LUAD samples showed that high expression of CA916798 was tightly correlated with pathological progression and poor prognosis of LUAD patients. A critical methylation site in promoter region of CA916798 gene was identified to be related with CA916798 gene expression. Forced expression of CA916798 relieved the inhibitory effects of WEE1 on CDK1 and facilitated cell cycle progression from G2 phase to M phase. However, knockdown of CA916798 enhanced WEE1 function and resulted in G2/M phase arrest. Consistently, chemical suppression of CDK1 dramatically inhibited G2/M phase transition in LUAD cells with high expression of CA916798. Finally, we found that CA916798 was highly expressed in Gefitinib-resistant LUAD cells. Exogenous expression of CA916798 was sufficient to endow Gefitinib resistance with tumor cells, but interference of CA916798 expression largely rescued response of tumor cells to Gefitinib. CONCLUSIONS: CA916798 played oncogenic roles and was correlated with the development of Gefitinib resistance in LUAD cells. Therefore, CA916798 could be considered as a promising prognostic marker and a therapeutic target for LUAD.

Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation.

BACKGROUND: Porana sinensis Hemsl. has been widely used as a substitute for Erycibes Caulis to treat rheumatoid arthritis (RA) in traditional Chinese medicine (TCM). However, little is known about the active ingredients and pharmacological mechanisms that mediate the action of P. sinensis against RA. METHODS: The compounds contained in P. sinensis were analyzed by Q Exactive Focus mass spectrometer. The active constituents and pharmacological mechanism of P. sinensis against RA were clarified using a network pharmacology-based investigation. LPS-induced RAW 264.7 cells was used to verify anti-inflammatory effects of the active compounds screened by network pharmacology. Collagen-induced arthritis model was used to further investigate the mechanism of P. sinensis against RA. RESULTS: The potential components and targets of P. sinensis against RA were analyzed using network pharmacology, and five compounds, twenty-five targets, and eight pathways were identified. Experimental validation suggested that P. sinensis extract and five compounds (esculetin, umbelliferone, trans-N-feruloyltyramine, caffeic acid and scopolin) could inhibit the release of inflammatory mediators (NO, TNF-α, IL-1ß and IL-6) in LPS-induced RAW 264.7 cell. P. sinensis extract attenuated the severity, pathological changes, and release of cytokines (IL-6 and HIF-1α) during RA progression by regulating the PI3K/AKT and HIF-1 pathways. CONCLUSION: The study provides a basis for the application of P. sinensis against RA. Our findings may provide suggestions for developing P. sinensis into a substitute for Erycibes Caulis.

The System Research of the Molecular Mechanism of Quyushengxin Capsule in the Treatment of Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that has a risk of eventually developing into a joint collapse and resulting in joint dysfunction. Quyushengxin capsule (QYSXC) is an effective and safe traditional Chinese medicine used in the treatment of ONFH. In this present study, an integrated approach was used to investigate the mechanism of QYSXC in the treatment of ONFH, which contained systems pharmacology, molecular docking, and chip experiment. In the systems pharmacology, target fishing, protein-protein interaction (PPI), Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, and herbs-compounds-targets-pathways (H-C-T-P) network construction were performed to study the mechanism of QYSXC in the treatment of ONFH. The results showed that 15 key compounds, 8 key targets, and 8 key signaling pathways were found for QYSXC in the treatment with ONFH. Then, molecular docking was performed to further explore the interaction between some key compounds and key targets. After that, the chip experiment was performed to verify some target factors, including ICAM-1, IL-6, IL-1α, IL-1ß, IL-2, IL-4, IL-10, and TNF-α. The results of this work may provide a theoretical basis for further research on the molecular mechanism of QYSXC in the treatment of ONFH.

Quyu Shengxin capsule (QSC) inhibits Ang-II-induced abnormal proliferation of VSMCs by down-regulating TGF-ß, VEGF, mTOR and JAK-STAT pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Quyu Shengxin capsule (QSC) is an herbal compound commonly used to treat blood stasis syndrome in China, and blood stasis syndrome is considered to be the root of cardiovascular diseases (CVD) in traditional Chinese medicine. However, the potential molecular mechanism of QSC is still unknown. AIM OF STUDY: To study the therapeutic effect of QSC on the abnormal proliferation of VSMCs induced by Ang-II, and to explore its possible mechanism of action. MATERIALS AND METHODS: Qualitative analysis and quality control of QSC through UPLC-MS/MS and UPLC. The rat thoracic aorta vascular smooth muscle cells (VSMCs) were cultured in vitro, and then stimulated with Angiotensin Ⅱ (Ang-II) (10-7 mol/L) for 24 h to establish a cardiovascular cell model. The cells were then treated with different concentrations of QSC drug-containing serum or normal goat serum. MTT assay was used to detect the viability of VSMCs and abnormal cell proliferation. In order to analyze the possible signal transduction pathways, the content of various factors in the supernatant of VSMCs was screened and determined by means of the Luminex liquid suspension chip detection platform, and the phosphoprotein profile in VSMCs was screened by Phospho Explorer antibody array. RESULTS: Compared with the model group, serum cell viability and inflammatory factor levels with QSC were significantly decreased (P < 0.001). In addition, the expression levels of TGF-ß, VEGF, mTOR and JAK-STAT in the QSC-containing serum treatment group were significantly lower than those in the model group. QSC may regulate the pathological process of CVD by reducing the levels of inflammatory mediators and cytokines, and protecting VSMCs from the abnormal proliferation induced by Ang-II. CONCLUSION: QSC inhibits Ang-II-induced abnormal proliferation of VSMCs, which is related to the down-regulation of TGF-ß, VEGF, mTOR and JAK-STAT pathways.

Efficacy and safety of Shufeng Jiedu capsule in the treatment of COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) epidemic is spreading worldwide. Shufeng Jiedu capsule (SFJDC) is a commonly used drug in the treatment of COVID-19. However, there is insufficient evidence for clinical efficacy and safety. METHODS: Two authors will independently search the Chinese National Knowledge Infrastructure (CNKI), VIP database, Wanfang database, the Cochrane Library, EMBASE, PubMed and Web of Science, in English and Chinese. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Review Manager 5.3 and Stata 16.0 software will be used to analyze the eligible data. RESULTS: This protocol will conduct a systematic review and meta-analysis of literature listed above, and reliable outcomes about the clinical efficacy and safety of SFJDC in the treatment of COVID-19 will be obtained. CONCLUSIONS: These findings will provide guidance for clinicians and patients using SFJDC for COVID-19 treatment. PROSPERO REGISTRATION NUMBER: CRD42020185764.

Assessing the explanatory and predictive performance of a random parameters count model with heterogeneity in means and variances.

Random parameters model has been demonstrated to be an effective method to account for unobserved heterogeneity that commonly exists in highway crash data. However, the predefined single distribution for each random parameter may limit how the unobserved heterogeneity is captured. A more flexible approach is to develop a random parameters model with heterogeneity in means and variances by allowing the mean and variance of potential each random parameter to be an estimable function of explanatory variables. This burgeoning technique for modelling unobserved heterogeneity has been increasingly applied to various safety evaluation scenarios recently. However, the predictive performance of this emerging method, which determines the practicability of the model for a specific circumstance, has never been investigated as far as our knowledge. In addition, the explanatory power by including heterogeneous means and variances of random parameters need to be further investigated to confirm the potential merits of this method in crash data analysis. In this paper, a random parameters negative binomial with heterogeneity in means and variances (RPNBHMV) model, a standard random parameters negative binomial (RPNB) model and a traditional fixed parameters negative binomial (NB) model were estimated using the same dataset. The explanatory and predictive performance of the three models were thoroughly evaluated and compared. Results showed that: 1) the RPNB model fitted the data significantly better than the NB model, and the RPNBHMV model further improved the statistical fit of the RPNB model but the improvement was slight; 2) more insights into interactions of safety factors were inferred from the RPNBHMV model, which demonstrates the explanatory benefit of this model; 3) the RPNBHMV and RPNB models had both advantages (e.g., produced overall better prediction accuracy) and disadvantages (e.g., provided reduced prediction accuracy across the range of explanatory variables) when applied to in-sample observations (i.e., observations used to estimate the model); 4) the RPNBHMV and RPNB models might be less precise than the NB model when applied to out-of-sample observations. These findings indicate that the RPNBHMV model offers more insights and may be used for explanatory safety analysis for sites where reliable data can be collected. However, the simple NB model is more reliable - at least with the dataset used in this study - than its random parameters model counterparts for other sites where the data are unavailable or unreliable, which is a common safety evaluation scenario in practice.

A Rapid, Accurate and Machine-Agnostic Segmentation and Quantification Method for CT-Based COVID-19 Diagnosis.

COVID-19 has caused a global pandemic and become the most urgent threat to the entire world. Tremendous efforts and resources have been invested in developing diagnosis, prognosis and treatment strategies to combat the disease. Although nucleic acid detection has been mainly used as the gold standard to confirm this RNA virus-based disease, it has been shown that such a strategy has a high false negative rate, especially for patients in the early stage, and thus CT imaging has been applied as a major diagnostic modality in confirming positive COVID-19. Despite the various, urgent advances in developing artificial intelligence (AI)-based computer-aided systems for CT-based COVID-19 diagnosis, most of the existing methods can only perform classification, whereas the state-of-the-art segmentation method requires a high level of human intervention. In this paper, we propose a fully-automatic, rapid, accurate, and machine-agnostic method that can segment and quantify the infection regions on CT scans from different sources. Our method is founded upon two innovations: 1) the first CT scan simulator for COVID-19, by fitting the dynamic change of real patients' data measured at different time points, which greatly alleviates the data scarcity issue; and 2) a novel deep learning algorithm to solve the large-scene-small-object problem, which decomposes the 3D segmentation problem into three 2D ones, and thus reduces the model complexity by an order of magnitude and, at the same time, significantly improves the segmentation accuracy. Comprehensive experimental results over multi-country, multi-hospital, and multi-machine datasets demonstrate the superior performance of our method over the existing ones and suggest its important application value in combating the disease.

Exploring multiple mechanisms of Qingjie Fanggan prescription for prevention and treatment of influenza based on systems pharmacology.

Influenza is a type of acute disease characterized by strong contagiousness and short incubation period, which have posed a large potential threat to public health. Traditional Chinese Medicine (TCM) advocates to the aim of combating complex diseases from a holistic view, which has shown effectiveness in anti-influenza. However, the mechanism of TCM prescription remains puzzling. Here, we applied a system pharmacology approach to reveal the underlying molecular mechanisms of Qingjie Fanggan prescription (QFP) in the prevention and treatment of influenza. In this study, we identified 228 potential active compounds by means of absorption, distribution, metabolism, and excretion (ADME) evaluation system and literature research. Then, the targets of the potential active compounds were predicted by using the WES (Weighted Ensemble Similarity) method, and the influenza-related targets were obtained according to some existing gene databases. Next, an herb-component-target network was constructed to further dissect the multi-directional therapeutic approach for QFP. Meanwhile, we also performed gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis on 344 potential targets. Finally, a target-pathway network was constructed to further dissect the core pathways and targets in treatment of influenza for QFP. And the key components and targets were docked by AutoDock Vina to explore their binding mode. All of these demonstrated that QFP had multi-scale curative activity in regulating influenza-related biological processes, which facilitates the application of traditional medicine in modern medicine.

Therapeutic efficacy of Qingfei Paidu decoction combined with antiviral drugs in the treatment of corona virus disease 2019: A protocol for systematic review and meta analysis.

BACKGROUND: The corona virus disease 2019 (COVID-19) has caused a global pandemic, there are no specific drugs and vaccines for epidemic control at present. More and more clinical practice shows that traditional Chinese medicine has played an important role in the outbreak. Among them, Qingfei Paidu decoction (QPD) combined with antiviral drugs can enhance the therapeutic efficacy for COVID-19. However, there is still a lack of comprehensive and systematic evidence, which urgently requires us to verify its therapeutic efficacy. Hence, we provide a protocol for systematic review and meta-analysis. METHODS: We will search the studies in MEDLINE/PubMed, China National Knowledge Infrastructure, Wanfang database, VIP database, the Cochrane Library, Chinese Biomedical Database and Chinese Science Citation Database. Searches are limited to clinical studies published in Chinese and English. Next, the quality of each study is assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Then, the outcome data are recorded and pooled by Review Manager 5.3 and STATA 16.0 software. RESULTS: The systematic review and meta-analysis aims to review and pool current clinical outcomes of QPD combined with antiviral drugs for the treatment of COVID-19. CONCLUSION: This study will provide a high-quality evidence of QPD for the treatment on COVID-19 patients. PROSPERO REGISTRATION NUMBER: CRD42020182409.

Efficacy and safety of Jinhua Qinggan granules for coronavirus disease 2019 (COVID-19): A protocol of a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS)-COV2 and represents the causative agent of a potentially fatal disease. Jinhua Qinggan granules has definite effect in treating COVID-19 patients, but it has not been systematically evaluated for efficacy and safety. METHODS: Retrieved the database, including the China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Evaluate methodological quality and judge risk of bias through the Cochrane manual. RevMan 5.3 and STATA 16.0 software were used to perform the meta-analysis. RESULTS: This study will provide high-quality evidence of Jinhua Qinggan granules for COVID-19. CONCLUSION: The conclusion of this study will provide evidence to determine whether Jinhua Qinggan granules is an effective treatment for COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020182373.

Therapeutic efficacy of shenmai injection as an adjuvant treatment in dilated cardiomyopathy: A protocol for systematic review.

BACKGROUND: Shenmai injection (SMI) is a Traditional Chinese Medicine patent prescription consisting of extractions from ophiopogonis radix and ginseng radix rubra. Clinical studies showed that SMI combined with conventional medicine treatment (CMT) can enhance the therapeutic efficacy for dilated cardiomyopathy (DCM). However, there is still a lack of comprehensive and systematic evidence, which urgently requires us to verify its therapeutic efficacy. Hence, we provide a protocol for systematic review and meta-analysis. METHODS: The systematic search on the MEDLINE/PubMed, China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, the Cochrane Library, Embase and Chinese Biomedical Database (CBM) in Chinese and English language with dates ranging from the earliest record to August 8, 2019. Next, the quality of each trial was assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Then, the outcome data were recorded and pooled by RevMan 5.3 software. RESULTS: The systematic review and meta-analysis aims to review and pool current clinical outcomes of SMI for the adjuvant treatment of DCM. CONCLUSION: This study will provide a high-quality evidence of SMI for the adjuvant treatment on DCM patients. PROSPERO REGISTRATION NUMBER: CRD42019146369.

Investigation of the mechanism of action of Porana sinensis Hemsl. against gout arthritis using network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Porana sinensis Hemsl. has been widely used to treat joint pain and rheumatoid arthritis in traditional Chinese medicine (TCM). Although evidence exists to support a pharmacological action of P. sinensis for the treatment of gout arthritis (GA), the underlying mechanism of action remains unknown due to it being a multi-component and multi-target agent. AIM OF THE STUDY: To clarify the active compounds and mechanism of P. sinensis against GA. MATERIALS AND METHODS: The present study combined network pharmacology with experiments to clarify the mechanism of P. sinensis against GA. A protein-protein interaction network for gout was constructed to identify the potential drug targets, and molecular docking was subsequently performed to determine whether the protein was a target for the compounds of P. sinensis. KEGG pathway analysis was then conducted to elucidate the pathway involved in the P. sinensis-mediated treatment of gout. A rat model of GA was used to further investigate the mechanism of P. sinensis against GA. RESULTS: The network pharmacology study indicates that coumarins and chlorogenic acids of P. sinensis may serve as additives to GA treatment. P. sinensis played a role in the treatment of GA by regulating the PI3K-Akt, MAPK, NF-kappa B and toll-like receptor pathways and so on. Moreover, experimental validation suggests that P. sinensis extract significantly suppressed the expression of TLR2 and MyD88 mRNA, regulating the release of cytokines (IL-1ß, IL-4 and TGF-ß), lowering lipid peroxidation (MDA) and increasing antioxidant status (SOD). CONCLUSION: The present study clarifies the mechanism of P. sinensis against GA, and provides evidence to support its clinical use.

Unraveling LGALS1 as a Potential Immune Checkpoint and a Predictor of the Response to Anti-PD1 Therapy in Clear Cell Renal Carcinoma.

Immunotherapy base on immune checkpoint inhibitor had obtained significant progress in extending the survival of clear cell renal carcinoma (ccRCC) patients. In order to further improve the efficiency of immunotherapy, novel immune checkpoint inhibitors needed to be developed. Differentially expressed genes (DEGs) between healthy kidney tissues and ccRCC tissues had been found from GSE68417 by GEO2R online analysis tool. Correlation analysis and Kaplan-Meier survival analyses were based on UALCAN database. Analyses of the outcome of anti-PD1 treatment had been found from GSE67501 dataset. At first, 9 genes with higher expression were associated with shorter overall survival time. More importantly, higher expression of LGALS1 was correlated with a profitable outcome of anti-PD1 treatment and the combined the expression level of PD-L1 and LGALS1 together could more efficiently predict the outcome of anti-PD1 treatment than using PD-L1 alone. At last, the genes which correlated with LGALS1 expression in ccRCC patients were enriched in TNF alpha Signaling Pathway which is mainly correlated with T cell apoptosis and survival. Together, these suggest LGALS1 could be a potential immune checkpoint, which could promote tumor progression through affecting T cell survival.

Physicochemical properties and immunological activities of polysaccharides from both crude and wine-processed Polygonatum sibiricum.

Polygonatum sibiricum (PS) is a traditional Chinese herb used in both food and medicine with great bioactivity. The wine-processed pieces of PS are the main form for clinical application, while research has focused on the polysaccharides of their crude form. This study evaluated the physicochemical properties and immunological activities of water-soluble polysaccharides from both crude (PSPC) and wine-processed PS (PSPW). PSPC and PSPW had significant differences in their physicochemical properties. PSPC was mainly composed of galactose, mannose, glucose, and galacturonic acid, in molar ratios of 29.63:36.10:15.09:10.20, while PSPW was mainly composed of galactose, mannose, and galacturonic acid, in molar ratios of 78.77:5.50:13.84. Both kinds of polysaccharides can enhance the cells viability, phagocytic capacity, acid phosphatase activity, and NO production of RAW264.7 cells. We found that PSPC and PSPW enhanced the immune functions of the immunosuppressive model for spleen deficient mice and reversed the decline of the secretions of IL-2, IL-6, TNF-α, and IFN-γ to a normal range. The PSPW showed more potent immunological activities than PSPC. The results of the study identify the importance of wine-processing for PS and provide application foundations for the further development of PSPW as a functional food.

Splenomegaly induced by anemia impairs T cell movement in the spleen partially via EPO.

The spleen is an important secondary lymph organ. Splenomegaly induced by anemia could affect the function of spleen in immune responses. We observe that anemia induced in mice with reduced peripheral T cell trafficking to the spleen T cell zones as well as CCL21 and CCL19 expression. In accordance with previous research, we found that the production of EPO in the mice kidney was sharply increased post anemia. In addition, mice were injected with different doses of EPO. Our results show that with the increased dosage of EPO, the chemokine expression in the spleen is lowered with a decrease in peripheral T cell homing to the spleen T cell zones. At last, our results show that the anemia mice model administrated with anti-EPO antibody had a higher expression of spleen CCL19 and CCL21 and an increased count of periphery T cells trafficking to spleen T cell zones at day 3 post induction. These data indicate that anemia could disturb T cell movement in the spleen, which might further affect T cell immune response, with partial involvement of EPO.