Astragaloside IV inhibits idiopathic pulmonary fibrosis through activation of autophagy by miR-21-mediated PTEN/PI3K/AKT/mTOR pathway.

As the main active ingredient of Astragalus, Astragaloside IV (AS-IV) can ameliorate pulmonary fibrosis. In this experiment, we studied how AS-IV reduces idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) or TGF-ß1 was treated in mice or alveolar epithelial cells to mimic IPF in vivo as well as in vitro. ASV-IV alleviated levels of inflammatory cytokines and fibrosis markers in IPF model. Through detection of autophagy-related genes, ASV-IV was observed to induce autophagy in IPF. Besides, ASV-IV inhibited miR-21 expression in IPF models, and overexpression of miR-21 could reverse the protective potential of ASV-IV on IPF. PTEN was targeted by miR-21 and was up-regulated by ASV-IV in IPF models. In addition, levels of inflammatory cytokines and fibrosis markers, autophagy, as well as the PI3K/AKT/mTOR pathway regulated by ASV-IV could be neutralized after treatment with autophagy inhibitors, miR-21 mimics, or si-PTEN. Our study demonstrates that ASV-IV inhibits IPF through activation of autophagy by miR-21-mediated PTEN/PI3K/AKT/mTOR pathway, suggesting that ASV-IV could be acted to be a promising therapeutic method for IPF.

A metabolic map and artificial intelligence-aided identification of nasopharyngeal carcinoma via a single-cell Raman platform.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a complex cancer influenced by various factors. This study explores the use of single-cell Raman spectroscopy as a potential diagnostic tool for investigating biomolecular changes associated with NPC carcinogenesis. METHODS: Seven NPC cell lines, one immortalised nasopharyngeal epithelial cell line, six nasopharyngeal mucosa tissues and seven NPC tissue samples were analysed by performing confocal Raman spectroscopic measurements and imaging. The single-cell Raman spectral dataset was used to quantify relevant biomolecules and build machine learning classification models. Metabolomic profiles were investigated using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). RESULTS: By generating a metabolic map of seven NPC cell lines, we identified an interplay of altered metabolic processes involving nucleic acids, amino acids, lipids and sugars. The results from spatially resolved Raman maps and UPLC-MS/MS metabolomics were consistent, revealing an increase of unsaturated fatty acids in cancer cells, particularly in highly metastatic 5-8F and poorly differentiated CNE2 cells. The classification model achieved a nearly perfect classification when identifying NPC and non-NPC cells with an ROC-AUC of 0.99 and a value of 0.97 when identifying 13 tissue samples. CONCLUSION: This study unveils a complex interplay of metabolic network and highlights the potential roles of unsaturated fatty acids in NPC progression and metastasis. This renders further research to provide deeper insights into NPC pathogenesis, identify new metabolic targets and improve the efficacy of targeted therapies in NPC. Artificial intelligence-aided analysis of single-cell Raman spectra has achieved high accuracies in the classification of both cancer cells and patient tissues, paving the way for a simple, less invasive and accurate diagnostic test.

How to tackle non-specific low back pain among adult patients? A systematic review with a meta-analysis to compare four interventions.

OBJECTIVE: To tackle non-specific low back pain (NSLBP) among patients and find the most effective solution and to quantitatively synthesize the overall effect of motor control training (MCT) compared with Pilates, McKenzie method, and physical therapy (PT) in pain and physical function. METHODS: Randomized controlled trials (RCTs) of four types of intervention (MCT, Pilates, McKenzie method, and PT) for LBP were collected by searching PubMed, Web of Science, EBSCOhost (Cochrane Central Register of Controlled Trials), and Scopus databases from the establishment of the database to September 30, 2023. The risk of bias was evaluated for included studies using the Revised Cochrane Risk of Bias tool for randomized trials (RoB 2.0). Taking pain and physical function in the experimental and control groups as outcome indicators, subgroup analysis was performed according to the intervention method to calculate the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 25 RCTs, including 1253 patients, were included. Meta-analysis showed that MCT effectively relieved pain [SMD = -0.65, 95% CI (- 1.00, - 0.29), p < 0.01] and improved physical function [SMD = -0.76, 95% CI (- 1.22, - 0.31), p < 0.01] comparing with other 3 types of intervention. Subgroup analysis suggested that MCT could alleviate pain [SMD = -0.92, 95% CI (- 1.34, - 0.50), p < 0.01] and improve physical function [SMD = -1.15, 95% CI (- 1.72, - 0.57), p < 0.01] compared with PT, but it had no statistical significance compared with Pilates [pain: SMD = 0.13, 95% CI (- 0.56, 0.83), p = 0.71; physical function: SMD = 0.10, 95% CI (- 0.72, 0.91), p = 0.81] and the McKenzie method [pain: SMD = -0.03, 95% CI (- 0.75, 0.68), p = 0.93; physical function: SMD = -0.03, 95% CI (- 1.00, 0.94), p = 0.95]. CONCLUSIONS: MCT can effectively relieve pain and improve physical function in patients with NSLBP. It is more effective compared with PT for LBP, while no differences were detected between MCT and Pilates, as well as McKenzie method. Therefore, MCT, Pilates, and the McKenzie method should be encouraged as exercise interventions for NSLBP rehabilitation.

A Real-World Study of Optimal Treatment with Anlotinib First-Line Therapy in Advanced Hepatocellular Carcinoma.

Purpose: To observe the efficacy and safety of anlotinib as a first-line treatment for patients with advanced hepatocellular carcinoma (aHCC) in a real-word environment, explore the optimal treatment regimen for patients with aHCC using anlotinib as a first-line treatment. Patients and Methods: Data from 62 patients with aHCC who received anlotinib single-drug first-line therapy between February 2019 and November 2021. Patients received anlotinib monotherapy, which may be interrupted or discontinued or changed in the event of unacceptable or severe adverse events (AEs) or failure to inhibit tumor progression. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate(ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Among the 62 patients, in the best overall response assessment, there were 12 with complete response (CR; 19.4%), 17 with partial response (PR; 27.4%), 25 with stable disease (SD; 40.3%), and 8 with progressive disease (PD; 14.5%). The ORR and DCR were 46.8% and 87.1%, respectively. Among the 11 patients who received tyrosine kinase inhibitors (TKIs) combined with programmed death 1 (PD-1) inhibitors after disease progression, three (27.3%) had CR, one (9.1%) had PR, three (27.3%) had SD, and four (36.4%) had PD. Therefore, the ORR and DCR were 36.4% and 63.6%, respectively. The median PFS for anlotinib monotherapy was 7.37 months (95% confidence interval [CI]: 5.88-8.86) and the median OS did not reach. AEs occurred in 95.2% of patients during anlotinib monotherapy, with the most common being thrombocytopenia (51.6%). The incidence of grade ≥3 AEs was 38.7%. Conclusion: Anlotinib is effective and well-tolerated as a first-line treatment for patients with aHCC. Treatment with TKIs and PD-1 inhibitors after disease progression has also shown preliminary efficacy and safety; therefore, sequential therapy with anlotinib-TKIs and PD-1 inhibitors may be an effective treatment for patients with aHCC.

Protective effects of liquiritin on UVB-induced skin damage in SD rats.

Overexposure to ultraviolet B (UVB) rays can cause damage to the skin. Liquiritin has a variety of pharmacological effects, such as anti-inflammatory and antioxidant. In the present study, the effect of liquiritin on UVB irradiated rat skin was investigated. Results showed that UVB irradiation caused erythema and wrinkles on the skin surface, as well as thickening and loss of elasticity of the epidermis and a significant increase in the level of ROS in the skin tissue. At the same time, western blot detected an increase in nuclear factor kappa-B (NF-κB) and matrix metalloproteinases (MMPs) and Elisa also detected an increase in pro-inflammatory factors. Therefore, we hypothesized that UVB irradiation-induced damage is associated with inflammation. Interestingly, application of liquiritin to exposed skin of rats reduced the increase in ROS, pro-inflammatory factors, and MMPs caused by UVB irradiation and increased the levels of Sirtuin3 (SIRT3) and Collagen α1. In addition, after intraperitoneal injection of the SIRT3 inhibitor 3-TYP in rats, the protective effect of liquiritin against UVB damage was found to be diminished. These results suggested that promotion of SIRT3 with liquiritin inhibits UVB-induced production of pro-inflammatory mediators, possibly acting through the SIRT3/ROS/NF-κB pathway. In conclusion, this study suggests that liquiritin is an effective drug candidate for the prevention of UVB damage.

Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis.

BACKGROUND: The NLRP3-mediated pyroptosis, which could be regulated by miRNA-27a, is a key player in the development of depression. Isoliquiritin is a phenolic flavonoid compound that has been demonstrated to suppress NLRP3-mediated pyroptosis. However, it is still unknown whether isoliquiritin could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by stimulating miRNA-27a. Thus, in the current study, we explored the antidepressant activity of isoliquiritin and its underlying mechanism. METHODS: Expression of miRNA-27a in depressed patients or mice was measured using qRT-PCR. Luciferase reporter assay was performed to illustrate the link between miRNA-27a and SYK. Lipopolysaccharide (LPS) and chronic social defeat stress (CSDS) depression models were established to investigate the antidepressant actions of isoliquiritin. Changes in miRNA-27a/SYK/NF-κB axis and NLRP3-mediated pyroptosis were also examined. The role of miRNA-27a in isoliquiritin-related antidepressant effect was further investigated by using miRNA-27a inhibitors and mimics of miRNA-27a. RESULTS: Our results showed the miRNA-27a expression was downregulated in the serum of depressed patients, and decreased serum and hippocampus expression of miRNA-27a were observed in rodent models of depression. SYK gene expression was significantly reduced by miRNA-27a mimic incubation. Isoliquiritin profoundly attenuated LPS or CSDS-induced depressive symptoms, as well as CSDS-induced anxiety behavior. In the hippocampus, LPS and CSDS decreased miRNA-27a mRNA expression; increased the protein levels of SYK, p-NF-κB, and NLRP3: cleaved Caspase-1, IL-1ß, and GSDMD-N: and elevated the concentration of IL-1ß, IL-6, and TNF-α, which were all restored by isoliquiritin administration. Meanwhile, isoliquiritin upregulated the hippocampal NeuN protein level, improved the survival and morphology of neurons, and decreased pyroptosis-related neuronal cell death. Moreover, isoliquiritin protected primary microglia against LPS and adenosine triphosphate (ATP) elicited NLRP3 inflammasome activation in vitro, evidenced by declined protein levels of p-NF-κB, NLRP3; cleaved Caspase-1, IL-1ß, and GSDMD-N; upregulated miRNA-27a mRNA expression; and decreased the mRNA and protein levels of SYK. Nevertheless, miRNA-27a inhibitors significantly reversed isoliquiritin-generated therapeutic efficacy in CSDS mice and in vitro. Furthermore, the cytoprotective effect of isoliquiritin was similar to that of miRNA-27a mimics in LPS and ATP-treated primary microglia. Taken together, these findings suggest that isoliquiritin possesses potent antidepressant property, which requires miRNA-27a/SYK/NF-κB axis controlled decrease of pyroptosis via NLRP3 cascade.

Risk factors for cancer-associated myositis: A large-scale multicenter cohort study.

AIM: The aim of this study was to identify the risk factors and prognosis of patients with cancer-associated myositis (CAM). METHOD: Four hundred and eighty-seven patients with dermatomyositis (DM), clinical amyopathic dermatomyositis (CADM) and polymyositis (PM) from 3 clinical centers were enrolled retrospectively in this study. Clinical and laboratory data of CAM and non-CAM patients were compared. Logistic regression analysis was used to identify risk factors of CAM. RESULTS: Out of the 487 patients with DM/CADM/PM, 7.0% (34/487) of patients were classified as CAM. Older age (53.91 ± 13.32 vs. 48.76 ± 14.34 years), heliotrope rash (61.8% vs. 41.9%), shawl sign (41.2% vs. 22.1%), V sign (58.8% vs. 38.6%) were observed significantly more commonly in patients with CAM than those without CAM (all P < .05). Fever (17.7% vs. 37.8%), arthralgia/arthritis (23.5% vs. 45.7%), interstitial lung disease (ILD, 38.2% vs 68.9%) were significantly less common in the CAM group than the non-CAM group. Age at onset (odds ratio [OR] 1.036, 95% CI 1.001-1.072, P = .042), shawl sign (OR 2.748, 95% CI 1.107-6.822, P = .029), anti-transition initiation factor (TIF)-1γ antibody (OR 4.012, 95% CI 1.268-12.687, P = .018) were identified as the initial risk factors for the onset of CAM, and ILD was identified as a protective factor for CAM (OR 0.292, 95% CI 0.115-0.739, P = .009). All-cause mortality was significantly higher in CAM patients compared with non-CAM patients (P = .001). CONCLUSION: The mortality of patients with CAM was higher than DM/CADM/PM patients without cancer. Malignancy should be screened in DM/CADM/PM patients especially with risk factors, including older age, shawl sign, anti-TIF-1γ antibody, and lack of ILD.

Predictors of Poor Outcome of Anti-MDA5-Associated Rapidly Progressive Interstitial Lung Disease in a Chinese Cohort with Dermatomyositis.

OBJECTIVE: Antimelanoma differentiation-associated protein 5 (anti-MDA5) autoantibody has been reported in dermatomyositis (DM) to be associated with rapidly progressive interstitial lung disease (RP-ILD). Our study is aimed at determining the clinical characteristics and prognostic factors underpinning anti-MDA5-associated RP-ILD. METHODS: Patients with anti-MDA5-associated DM (aMDA5-DM) were identified at the Peking University People's Hospital. The presence of anti-MDA5 antibody was determined by immunoblotting. Kaplan-Meier, chi-square test, univariate, and multivariate data analyses were used. RESULTS: Out of 213 patients with DM and clinically amyopathic dermatomyositis (CADM), 20.7% (44/213) of patients were identified as aMDA5-DM. Amongst the aMDA5-DM patients, 63.6% (28/44) were identified as having anti-MDA5-associated RP-ILD. During the follow-up, 32.1% (9/28) of patients with anti-MDA5-associated RP-ILD died of respiratory failure. We identified older age and periungual erythema as two independent risk factors for RP-ILD mortality. Age ≥ 57 years at disease onset was significantly associated with poor survival (P = 0.02) in patients with anti-MDA5-associated RP-ILD, while patients with periungual erythema had a better survival rate than those without periungual erythema (P < 0.05). CONCLUSIONS: Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates in DM/CADM patients. More effective intervention should be administered to anti-MDA5-associated RP-ILD patients, especially to senior patients and those without periungual erythema.

Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest.

Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB1 (300 µg/kg/day for 30 days). The toxicity of AFB1 on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB1 on IMR-32 cells were 6.18 µg/mL and 5.87 µg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB1 concentration-dependent manner, which was associated with the upregulation of NOX2, and downregulation of OXR1, SOD1, and SOD2. Substantial DNA damage associated with the downregulation of PARP1, BRCA2, and RAD51 was also observed. Furthermore, AFB1 significantly induced S-phase arrest, which is associated with the upregulation of CDKN1A, CDKN2C, and CDKN2D. Finally, AFB1 induced apoptosis involving CASP3 and BAX. Taken together, AFB1 manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis-all of which are key factors for understanding the neurotoxicology of AFB1.

Predictors and Mortality of Rapidly Progressive Interstitial Lung Disease in Patients With Idiopathic Inflammatory Myopathy: A Series of 474 Patients.

Objective: This study was conducted to identify the characteristics and prognosis of rapidly progressive interstitial lung disease (RP-ILD) in idiopathic inflammatory myopathy (IIM) and to assess the predictors for poor survival of RP-ILD in IIM. Methods: A total of 474 patients with IIM were enrolled retrospectively according to medical records from Peking University People's Hospital. Clinical and laboratory characteristics recorded at the diagnosis of patients with RP-ILD and chronic ILD (C-ILD) were compared. The Kaplan-Meier estimator and univariate and multivariate analyses were used for data analysis. Results: ILD was identified in 65% (308/474) of patients with IIM. Patients with ILD were classified into two groups based on lung features: RP-ILD (38%, 117/308) and C-ILD (62%, 191/308). RP-ILD resulted in significantly higher mortality in IIM compared with C-ILD (27.4 vs. 7.9%, P < 0.05). In this study, by comparing IIM patients with and without RP-ILD, a list of initial predictors for RP-ILD development were identified, which included older age at onset, decreased peripheral lymphocytes, skin involvement (periungual erythema, skin ulceration, and subcutaneous/mediastinal emphysema), presence of anti-MDA5 antibody, serum tumor markers, etc. Further multivariate Cox proportional hazards model analysis identified that anti-MDA5 positivity was an independent risk factor for mortality due to RP-ILD (P < 0.05), and lymphocytes <30% in BALF might also be associated with poor survival of myositis-associated RP-ILD (P < 0.05). Conclusion: Our study shows that RP-ILD results in increased mortality in IIM. Anti-MDA5 positivity and a lower lymphocyte ratio in BALF might be the predictive factor of mortality due to RP-ILD.

Urinary neutrophil gelatinase-associated lipocalin rapidly decreases in the first week after kidney transplantation.

BACKGROUND: Recipient delayed graft function, which is defined as dialysis in the first week after transplantation, is one of the most common early complications after kidney transplantation. This study aimed to evaluate the daily changes in renal function-related biomarkers in the first week post-transplant. METHODS: A total of 72 kidney transplant recipients were retrospectively included in this study. Clinical and laboratory data were collected daily during the first week post-transplant, including urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL), serum concentrations of NGAL, creatinine, urea nitrogen, uric acid (UA), ß2-microglobulin, cystatin C, and estimated glomerular filtration rate (eGFR). RESULTS: There were no significant differences in urea nitrogen (P = .375), UA (P = .090), and cystatin C (P = .691), while urinary NGAL (P < .0001), serum NGAL (P < .0001), creatinine (P < .0001), ß2-microglobulin (P < .0001), and eGFR (P < .0001) were statistically significant in the first week post-transplant. In comparison with serum NGAL (P < .0001), creatinine (P < .0001), ß2-microglobulin (P = .001), and eGFR (P = .001), the change ratios of urinary NGAL changed the most between day 1 and day 2 after renal transplantation, while the changing degree of urinary NGAL showed no significant difference compared with these indicators between day 1 and day 7 after kidney transplantation. CONCLUSION: Urinary NGAL is a sensitive marker for indicating renal function. Urinary NGAL combined with other markers can be more helpful for evaluating renal function in the first week following kidney transplantation.

Astragalin Exerted Antidepressant-like Action through SIRT1 Signaling Modulated NLRP3 Inflammasome Deactivation.

Inflammation plays a key role in the pathogenesis of depression and antidepressant therapies. Astragalin (AST) is a bioactive flavonoid that possesses an anti-inflammatory property. However, the antidepressant action of astragalin has not been addressed. In this study, we explored the antidepressant effects of astragalin and its underlying mechanism. Our results showed that AST significantly improved the behavioral defects in chronic unpredictable mild stress (CUMS) model, promoted SIRT1 expression, and decreased the protein levels of NF-κB p65, NLRP3, cleaved capase-1, cleaved IL-1ß and cleaved gasdermin D in the hippocampus. Immunohistochemistry revealed AST mitigated CUMS-induced microglia overactivation. In vitro, AST profoundly increased the cell viability in lipopolysaccharides (LPS) and adenosine triphosphate (ATP) treated BV2 cells, with upregulated SIRT1 expression and downregulated protein levels of nuclear NF-κB p65, NLRP3, cleaved capase-1, and cleaved gasdermin D. Declined cleavage of gasdermin D was observed after AST administration in immunocytochemistry. Nevertheless, the in vivo and in vitro effects of AST were compromised by SIRT1 inhibitor EX-527. These results indicated that AST possessed an antidepressant property, which was dependent on SIRT1 signaling modulated NLRP3 inflammasome deactivation.

Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides L., which is called Kudouzi in China, is a medicinal plant distributed in Western and Central Asia, especially in China, and has been used for decades to treat fever, bacterial infection, heart disease, rheumatism, and gastrointestinal diseases. AIM OF THE REVIEW: This review aims to provide up-to-date information on S. alopecuroides, including its botanical characterization, medicinal resources, traditional uses, phytochemistry, pharmacological research, and toxicology, in exploring future therapeutic and scientific potentials. MATERIALS AND METHODS: The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, PhD and MS dissertations, and other web sources, such as the official website of Flora of China and Yao Zhi website (https://db.yaozh.com/). RESULTS: A total of 128 compounds, such as alkaloids, flavonoids, steroids, and polysaccharides, were isolated from S. alopecuroides. Among these compounds, the effects of alkaloids, such as matrine and oxymatrine, were extensively studied and developed into new drugs. S. alopecuroides and its active components had a wide range of pharmacological activities, such as anticancer, antiviral, anti-inflammatory, antimicrobial, analgesic, and neuroprotective functions, as well as protective properties against pulmonary fibrosis and cardiac fibroblast proliferation. CONCLUSIONS: As an important traditional Chinese medicine, modern pharmacological studies have demonstrated that S. alopecuroides has prominent bioactivities, especially on gynecological inflammation and hepatitis B, and anticancer activities. These activities provide prospects for novel drug development for cancer and some chronic diseases. Nevertheless, the comprehensive evaluation, quality control, understanding of the multitarget network pharmacology, long-term in vivo toxicity, and clinical efficacy of S. alopecuroides require further detailed research.

[Correlation of Nucleostemin with Programmed Death-ligand-1 in Multiple Myeloma U266 Cells].

OBJECTIVE: To investigate the correlation of nucleostemin (NS) gene with programmed death ligand-1 (PD-L1) in myeloma cells and the effect of NS expression down-regulation on the apoptosis of multiple myeloma cells, and to evaluate the associations among NS, PD-L1 and biological behavior of MM cells, and the feasibility of both NS and PD-1 as markers reflecting the status of MM cells. METHODS: The NS gene expression in U266 cells was down-regulated by NS-RNAi-GV248 recombinant lentivirus, the real-time PCR was used to detect the mRNA expression of NS, PD-L1 and PI3K/AKT/mTOR. The Western blot and flow cytometry were used to detect the expression of NS and PD-L1. The Annexin V-APC/7-AAD staining method was used to detect the apoptosis of U266 cells before and after knocking out the NS gene. RESULTS: Under the condition of MOI=10, the transfection efficiency was more than 75% by means of the fluorescent microscopy; real-time PCR showed that compared with the negative control group (1.002±0.026), the mRNA expression of NS, PD-L1 and PI3K/AKT/mTOR gene in the transfection group (0.415±0.089) was significantly reduced (P＜0.05). The results of flow cytometry and Western blot showed that the protein expression of PD-L1 was significantly down-regulated after transfection. After down-regulation of NS gene expression, the apoptosis of U266 cells increased (P＜0.05). CONCLUSION: The abnormal high expression of NS and PD-L1 genes exists in U266 cells, moreover, the down-regulation of PD-L1 and the related PISK/AKT/mTOR pathway gene expression appears after down-regulation of NS gene expression, which suggest that the cell biological changes resulted from above-mentioned results, show a synergestic effect on U266 cells.

Enrichment of circulating myeloma cells by immunomagnetic beads combined with flow cytometry for monitoring minimal residual disease and relapse in patients with multiple myeloma.

Difficulty in regularly analyzing marrow myeloma cells (MMCs) and low frequency of circulating myeloma cells (CMCs) in blood presents challenges for monitoring minimal residual disease (MRD) in multiple myeloma (MM). We have developed a set of method for enrichment of CMCs by immunomagetic beads (IMB) combined with flow cytometry (IMB-FCM) based on CD38-APC/CD138-APC antibodies in U266-spiked samples and in 122 patient samples. U266 cell capture efficiency of CD38/CD138-IMB-FCM (6.960, 2.574) was 6- and 2-fold higher than that of FCM (1.032), and the sensitivity of FCM and IMB-FCM was 0.01% and 0.001%, respectively. In MM cohort, the positive rate of CMCs by IMB-FCM increased from 60.5~70.0 to 85~87.2% in newly diagnosed/relapsed and partial remission (PR) patients compared with by FCM (P < 0.05). Two complete remission (CR) patients contain certain amounts of CMCs by IMB-FCM while no CMCs and MMCs were detectable by FCM. Patients exhibiting PR and CR upon therapy had much lower CMC and MMC counts than newly diagnosed/relapsed patients (P < 0.005). Based on MRD measurement in BM and PB samples, all FCM-negative BM samples were also paired with FCM/IMB-FCM-negative PB samples among newly diagnosed, relapsed, and PR patients, and FCM-positive BM samples were accompanied by IMB-FCM-positive results in 88% of corresponding PB samples. CMCs strongly associated with other clinical biomarkers of disease burden, including elevated MMCs, ß2-MG, sCrea, and DS and ISS stages, and more serious anemia, bone destruction, and renal impairment (P < 0.05). Logistic regression analysis revealed that elevated ß2-MG and moderate-to-more anemia were significant risk factors for the presence of CMCs (P < 0.05). As a noninvasive "liquid biopsy" of monitoring MRD, the potential of IMB-FCM for CMC detection may complement or minimize bone marrow aspiration in future treatment of MM patients.

Phytochemical Information and Biological Activities of Quinolizidine Alkaloids in Sophora: A Comprehensive Review.

Quinolizidine alkaloids, a main form of alkaloids found in the genus Sophora, have been shown to have many pharmacological effects. This review aims to summarize the photochemical reports and biological activities of quinolizidine alkaloids in Sophora. The collected information suggested that a total of 99 quinolizidine alkaloids were isolated and detected from different parts of Sophora plants, represented by lupinine-type, cytisine-type, sparteine-type, and matrine-type. However, quality control needs to be monitored because it could provide basic information for the reasonable and efficient use of quinolizidine alkaloids as medicines and raw materials. The nonmedicinal parts may be promising to be used as a source of quinolizidine alkaloid raw materials and to reduce the waste of resources and environmental pollution. In addition, the diversity of chemical compounds based on the alkaloid scaffold to make a biological compound library needs to be extended, which may reduce toxicity and find new bioactivities of quinolizidine alkaloids. The bioactivities most reported are in the fields of antitumor activity along with the effects on the cardiovascular system. However, those studies rely on theoretical research, and novel drugs based on quinolizidine alkaloids are expected.

The antidepressant effects of hesperidin on chronic unpredictable mild stress-induced mice.

Hesperidin, a kind of citrus bioflavonoid distributed in foods including grapefruits, oranges and lemons, has many pharmacological activities. This study was aimed to evaluate the anti-depressant-like effect of hesperidin on chronic unpredictable mild stress (CUMS)-induced mice. Depressive-like behavior was detected by the sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST). A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to assess the cell viability of corticosterone-induced PC12 cells. The serum, hippocampal and cell supernatant concentrations of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were determined using enzyme-linked immunosorbent assay (ELISA) commercial kits. Furthermore, the protein expression levels of high-mobility group box 1 protein (HMGB1), receptor for advanced glycation end-products (RAGE)/NF-κB and brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway in the hippocampus and corticosterone-induced PC12 cells were detected by Western blot. Our results showed that hesperidin (100, 200 mg/kg) significantly relieved depressive-like behaviors, including decreased sucrose consumption in sucrose preference test (SPT), immobility in the forced swimming test (FST), tail suspension test, and locomotor activity in the open field test (OFT). Hesperidin reduced inflammatory cytokine levels by attenuating the HMGB1/RAGE/NF-κB signaling pathway and BDNF/TrkB pathway both in vivo and in vitro. In conclusion, hesperidin possessed efficient neuroprotective effects on depression, which was associated with neuroinflammation mediated by the HMGB1/RAGE/NF-κB and BDNF/TrkB pathways.

Prognostic value of miR17-92 family in patients with digestive system cancers: a systematic review and meta-analysis.

The miR17-92 family is found to be aberrantly expressed and associated with clinicopathological characteristics in patients with various cancers, including digestive system cancers. However, its prognostic value is not yet established. Therefore, we performed a systematic review and meta-analysis to investigate the association between miR17-92-family expression and clinical outcomes in digestive system cancers. We searched the PubMed, Web of Science, Embase, and CNKI (Chinese) databases to retrieve eligible studies up to June 30, 2018. Prognostic data and clinicopathological features of overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were extracted to evaluate correlations of the miR17-92 family with digestive system cancers. We used HRs to assess association between miR17-92-family expression and cancers prognosis. A total of 30 qualifying studies involving 4,056 subjects were included in this meta-analysis. Our results indicated that expression levels of miR17-92 can predict poor OS (HR 1.21, 95% CI 1.03-1.39; P=0). However, there was no relationship between the miR17-92 family and DFS (HR 0.86, 95% CI 0.6-1.11; P=0.170) or PFS (HR 1.37, 95% CI 0.83-1.91; P=0). Moreover, miR17-92 was related to TNM stage (III/IV vs I/II, HR 1.37, 95% CI 1.17-1.570; P=0.012), but there was no relationship between miR17-92 and metastasis (HR 1.64, 95% CI 1.34-1.95; P=0.491) or tumor size (≥5 cm vs <5 cm, HR 1.29, 95% CI 1.09-1.49; P=0.586). Subgroup analysis showed that miR17-92 expression was associated with poor OS among the Chinese subgroup (HR 1.28, 95% CI 1.08-1.48; P=0) and tissue samples (HR 1.12, 95% CI 0.93-1.31; P=0), while there was no association with other characteristics. Our results indicated that miR17-92 expression is significantly associated with poor survival in patients with digestive system cancers, suggesting that miR17-92 may be a promising prognostic marker to monitor prognosis and progression of cancers.

Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis: A retrospective cohort study.

AIM: To evaluate the long-term efficacy and safety of autologous stem cell transplantation (SCT) for decompensated liver cirrhosis. METHODS: Consecutive patients with decompensated liver cirrhosis were included and assigned into the SCT group and non-transplantation (non-SCT) group according to whether they received SCT treatment. Patients were followed up for ten years. The long-term survival rate and incidence of hepatocellular carcinoma (HCC) were compared between groups. RESULTS: A total of 159 patients were enrolled, including 27 cases in the SCT group and 132 cases in the non-SCT group. The baseline characteristics were significantly different between the two groups. Propensity score matching (PSM) was used to match SCT and non-SCT patients. After PSM, 92 subjects were enrolled in the final analysis, including 23 cases in the SCT group and 69 cases in the non-SCT group. The overall mortality was 73.9% and 55.1%, and the median survival period was 48 and 64 mo, respectively. However, no significant difference was found in the long-term survival rate between the two groups (P > 0.05). In addition, the incidence of HCC was higher in the SCT group than in the non-SCT group (47.8% vs 21.7%, P < 0.05). After adjusting for other covariates, SCT (OR = 3.065, 95%CI: 1.378-6.814) and age (OR = 1.061, 95%CI: 1.021-1.102) were independently correlated with the development of HCC in this decompensated liver cirrhosis cohort. CONCLUSION: Autologous SCT may fail to improve the long-term efficacy and increase the incidence of HCC for decompensated liver cirrhosis. Close monitoring of HCC is strongly recommended in patients undergoing autologous SCT.

Clinical characteristics and prognostic significance of EBER positivity in diffuse large B-cell lymphoma: A meta-analysis.

Recent studies show that Epstein-Barr virus (EBV) positivity might be related to adverse prognosis in patients with diffuse large B-cell lymphoma (DLBCL), but the results are still inconclusive. We conducted this meta-analysis to define the clinical value of EBV infection in DLBCL. All potential articles in PubMed, Web of Science, Medline, and Embase were retrieved. Using the random-effects or fixed-effect model, pooled hazard ratios (HRs) or relative risk (RR) with 95% confidence intervals (CIs) were used to calculate the correlation between EBER and prognosis and clinical features in DLBCL. A total of 13 qualified studies with 4111 patients were identified in our meta-analysis based on the inclusion and exclusion criteria. The overall estimates revealed that EBV-encoded small RNAs (EBER) positivity was significantly correlated with worse overall survival (HR = 2.43, 95% CI: 1.73-3.36) and progression-free survival (HR = 3.60, 95% CI: 2.07-6.26). In addition, EBER positivity was associated with age older than 60 years (RR = 1.51, 95% CI: 1.02-2.24), male sex (RR = 1.34, 95% CI: 1.05-1.71), more advanced stage (RR = 2.25, 95% CI: 1.72-2.96), high international prognostic index (RR = 2.20, 95% CI: 1.71-2.82), more than one extranodal involvement (RR = 1.69, 95% CI: 1.27-2.26), presence of B symptom (RR = 1.75, 95% CI: 1.30-2.35), non-germinal center B-cell subtype (RR = 1.35, 95% CI: 1.03-1.78), and elevated lactate dehydrogenase levels (RR = 1.30, 95% CI: 0.98-1.72). EBER positivity was correlated with worse outcomes, worse clinical course, and adverse clinicopathologic features among patients with DLBCL.