Research progress on ethnobotany, phytochemistry, pharmacological action, and applications of Engelhardia roxburghiana Wall: a review.

OBJECTIVES: Engelhardia roxburghiana Wall is a plant of the Juglandaceae family, and its leaves is the main part used as a medicine. It is used to relieve heat and pain, gasification, and dampness. The purpose of this review is to provide a systematic review about the botany, traditional uses, phytochemistry, pharmacology, and toxicology of this plant. KEY FINDINGS: Many compounds have been isolated and identified from the plant, including flavonoids, triterpenoids, steroids, quinones, essential oils, and other types of chemical constituents. Extensive pharmacological activities of the extracts or compounds of E. roxburghiana Wall in vivo and in vitro were mainly confirmed, including anti-cancer, anti-diabetic, anti-inflammatory, and anti-allergic effects. SUMMARY: In this paper, the botany, traditional uses, phytochemistry, and pharmacology of E. roxburghiana Wall were reviewed. In the future, E. roxburghiana Wall needs further study, such as paying more attention to quality control and the utilization on agriculture. In addition, discussing the medicinal components of decoction as well as the toxicity will also contribute to the progress of clinical trial studies.

Pycallingcards: an integrated environment for visualizing, analyzing, and interpreting Calling Cards data.

MOTIVATION: Unraveling the transcriptional programs that control how cells divide, differentiate, and respond to their environments requires a precise understanding of transcription factors' (TFs) DNA-binding activities. Calling cards (CC) technology uses transposons to capture transient TF binding events at one instant in time and then read them out at a later time. This methodology can also be used to simultaneously measure TF binding and mRNA expression from single-cell CC and to record and integrate TF binding events across time in any cell type of interest without the need for purification. Despite these advantages, there has been a lack of dedicated bioinformatics tools for the detailed analysis of CC data. RESULTS: We introduce Pycallingcards, a comprehensive Python module specifically designed for the analysis of single-cell and bulk CC data across multiple species. Pycallingcards introduces two innovative peak callers, CCcaller and MACCs, enhancing the accuracy and speed of pinpointing TF binding sites from CC data. Pycallingcards offers a fully integrated environment for data visualization, motif finding, and comparative analysis with RNA-seq and ChIP-seq datasets. To illustrate its practical application, we have reanalyzed previously published mouse cortex and glioblastoma datasets. This analysis revealed novel cell-type-specific binding sites and potential sex-linked TF regulators, furthering our understanding of TF binding and gene expression relationships. Thus, Pycallingcards, with its user-friendly design and seamless interface with the Python data science ecosystem, stands as a critical tool for advancing the analysis of TF functions via CC data. AVAILABILITY AND IMPLEMENTATION: Pycallingcards can be accessed on the GitHub repository: https://github.com/The-Mitra-Lab/pycallingcards.

Bacillus cereus G2 Facilitates N Cycle in Soil, Further Improves N Uptake and Assimilation, and Accelerates Proline and Glycine Betaine Metabolisms of Glycyrrhiza uralensis Subjected to Salt Stress.

Soil salinity is a severe abiotic stress that reduces crop productivity. Recently, there has been growing interest in the application of microbes, mainly plant-growth-promoting bacteria (PGPB), as inoculants for saline land restoration and plant salinity tolerance. Herein, the effects of the plant endophyte G2 on regulating soil N cycle, plant N uptake and assimilate pathways, proline and glycine betaine biosynthesis, and catabolic pathways were investigated in Glycyrrhiza uralensis exposed to salinity. The results indicated that G2 improved the efficiency of N absorption and assimilation of plants by facilitating soil N cycling. Then, G2 promoted the synthesis substrates of proline and glycine betaine and accelerated its synthesis rate, which increased the relative water content and reduced the electrolyte leakage, eventually protecting the membrane system caused by salt stress in G. uralensis. These findings will provide a new idea from soil to plant systems in a salinity environment.

Emerging trends of BCG immunotherapy for bladder cancer in last decade: a bibliometric and visualization analysis.

Background: One of the milestones in bacterial-mediated therapy for cancer, Bacillus Calmette-Guerin (BCG) has been used to treat bladder cancer (BC) for more than 30 years. BCG immunotherapy is now the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) following transurethral resection. Methods: We searched the Web of Science core collection (WoSCC) database and used bibliometric methods through CiteSpace (version 5.1.R6), VOSviewer (version 1.6.18) and R-Bibliometrix (version R 4.2.1) to analyze and discuss the current status and trends of BCG therapy of BC from 2012 to 2021 in terms of co-occurrence, co-polymerization and visualization. Results: A total of 2476 publications were found, with the majority coming from the United States and China. Over the last decade, overall yearly outputs have increased fivefold, from 117 papers in 2012 to 534 records in 2021. Most publications were produced by the University of Texas System. The authors, Ashish M. Kamat of the University of Texas-MD Anderson Cancer Center in the United States, and Shahrokh F. Shariat of Weill Cornell Medical College, were pioneers in this field with the most publications. The journals, Urologic Oncology Seminars and Original Investigations, Cancers and Frontiers in Oncology, have published a dramatic increase in the number of articles, and tumor and urology nephrology research directions have received the most attention from journals. Furthermore, recent research has concentrated on muscle-invasive bladder cancer (MIBC). BCG therapy mechanism, BCG dose and strains, targeted therapy and immune checkpoint inhibitors (ICIs) for BC were attractive research contents, with ICIs (PD-1, PD-L1) being the most popular study point in recent years. With more research on tumor immunology, screening for more reliable biomarkers for precision treatment, and the development of combination regimens of ICIs, targeted treatment of BC stem cells, and personalized BC therapies may be promising areas of immunotherapy research in the coming years. Conclusion: The results of this bibliometric study can provide the current status and research trends of BCG therapy for BC in the last decade, and also further complements the research content of bacterial-mediated cancer therapy.

Improvement in bacterial cellulose production by co-culturing Bacillus cereus and Komagataeibacter xylinus.

Bacterial cellulose (BC) is a bio-produced nanostructure material widely used in biomedical, food, and paper-manufacturing industries. However, low production efficiency and high-cost have limited its industrial applications. This study aimed to examine the level of improvement in BC production by co-culturing Bacillus cereus and Komagataeibacter xylinus. The BC yield in corn stover enzymatic hydrolysate was found to be obviously enhanced from 1.2 to 4.4 g/L after the aforementioned co-culturing. The evidence indicated that acetoin (AC) and 2,3-butanediol (2,3-BD) produced by B. cereus were the key factors dominating BC increment. The mechanism underlying BC increment was that AC and 2,3-BD increased the specific activity of AC dehydrogenase and the contents of adenosine triphosphate (ATP) and acetyl coenzyme A (acetyl-CoA), thus promoting the growth and energy level of K. xylinus. Meanwhile, the immobilization of BC could also facilitate oxygen acquisition in B. cereus under static conditions. This study was novel in reporting that the co-culture could effectively enhance BC production from the lignocellulosic enzymatic hydrolysate.

Overexpression of cannabinoid receptor 2 is associated with human breast cancer proliferation, apoptosis, chemosensitivity and prognosis via the PI3K/Akt/mTOR signaling pathway.

INTRODUCTION: The cannabinoid receptor 2 (CB2) is mainly involved in the immune system. However, although CB2 has been reported to play an anti-tumor function in breast cancer (BC), its specific mechanism in BC remains unclear. METHODS: We examined the expression and prognostic significance of CB2 in BC tissues by qPCR, second-generation sequencing, western blot, and immunohistochemistry. We assessed the impacts of overexpression and a specific agonist of CB2 on the growth, proliferation, apoptosis, and drug resistance of BC cells in vitro and in vivo using CCK-8, flow cytometry, TUNEL staining, immunofluorescence, tumor xenografts, western blot, and colony formation assays. RESULTS: CB2 expression was significantly lower in BC compared with paracancerous tissues. It was also highly expressed in benign tumors and ductal carcinoma in situ, and its expression was correlated with prognosis in BC patients. CB2 overexpression and treatment of BC cells with a CB2 agonist inhibited proliferation and promoted apoptosis, and these actions were achieved by suppressing the PI3K/Akt/mTOR signaling pathway. Moreover, CB2 expression was increased in MDA-MB-231 cell treated with cisplatin, doxorubicin, and docetaxel, and sensitivity to these anti-tumor drugs was increased in BC cells overexpressing CB2. CONCLUSIONS: These findings reveal that CB2 mediates BC via the PI3K/Akt/mTOR signaling pathway. CB2 could be a novel target for the diagnosis and treatment of BC.

S100A1 expression is increased in spinal cord injury and promotes inflammation, oxidative stress and apoptosis of PC12 cells induced by LPS via ERK signaling.

Spinal cord injury (SCI) is a severe neurological disorder and the molecular mechanisms leading to its poor prognosis remain to be elucidated. S100A1, a mediator of Ca2+ handling of sarcoplasmic reticulum and mitochondrial function, operates as an endogenous danger signal (alarmin) associated with inflammatory response and tissue injury. The aim of the present study was to investigate the expression and biological effects of S100A1 in SCI. A rat model of SCI and a PC12 cell model of lipopolysaccharide (LPS)­induced inflammation were established to examine S100A1 expression at the mRNA and protein levels. The inflammation level, which was mediated by S100A1, was determined based on inflammatory factor (IL­1ß, IL­6 and TNF­α) and anti­inflammatory factor (IL­10) expression. The effects of S100A1 on cellular oxidation and anti­oxidation levels were observed by detecting the levels of reactive oxygen species, superoxide dismutase, catalase activities and nuclear factor erythroid 2­related factor 2 expression. The protein levels of Bax, Bcl2 and cleaved caspase­3 were used for the evaluation of the effects of S100A1 on apoptosis. Phosphorylated (p­)ERK1/2 expression was used to evaluate the effects of S100A1 on ERK signaling. The results revealed that S100A1 expression was significantly upregulated in vivo and in vitro in the PC12 cell model of LPS­inflammation. The silencing and overexpression of S100A1 helped alleviate and aggravate LPS­induced inflammation, oxidative stress and apoptosis levels, respectively. S100A1 was found to regulate the ERK signaling pathway positively. An inhibitor of ERK signaling (MK­8353) partially abolished the promoting effects of the overexpression of S100A1 on inflammation, oxidative stress damage and apoptosis. In conclusion, S100A1 expression was elevated in model of SCI and in the PC12 cell model of LPS­induced inflammation. Furthermore, the overexpression/silencing S100A1 aggravated/mitigated the inflammation, oxidative stress damage and the apoptosis of LPS­stimulated PC12 cells via the ERK signaling pathway. The present study revealed the mechanism of S100A1 in SCI, which provided a new theoretic reference for future research on SCI.

The relationship between bladder storage function and frequent micturition after TURP.

PURPOSE: To investigate the relationship between preoperative bladder function and frequent micturition after transurethral resection of prostate in patients with benign prostatic hyperplasia. METHODS: We retrospectively included 80 eligible patients aged 54-87 years (mean age 69.8 years) who underwent transurethral resection of the prostate at our hospital from January 2019 to October 2021. Patients were divided into detrusor overactivity positive and negative groups, and according to bladder compliance, they were divided into: low (G1), normal (G2), and high (G3) bladder compliance groups. RESULTS: The incidence and score of postoperative frequent micturition in the detrusor overactivity positive group were higher than those in the detrusor overactivity negative group. The incidence and score of postoperative frequent micturition in the low bladder compliance group were higher than those in the normal and high bladder compliance groups. There was no significant difference in the score of frequent micturition between the normal and high bladder compliance groups. Multivariate logistic regression analysis indicated that frequent micturition was significantly correlated with detrusor overactivity, bladder compliance, maximum cystometric capacity, and maximum flow rate. CONCLUSION: This study confirmed that patients with abnormal bladder storage functions (detrusor instability and low bladder compliance) before transurethral resection of the prostate were likely to have frequent and severe urination after transurethral resection of the prostate. Therefore, preoperative urodynamic examination to evaluate the urinary storage function of patients with benign prostatic hyperplasia is of great significance to predict the occurrence and degree of postoperative frequent micturition.

Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common histological and devastating subtype of renal cell carcinoma. Necroptosis is a form of programmed cell death that causes prominent inflammatory responses. miRNAs play a significant role in cancer progression through necroptosis. However, the prognostic value of necroptosis-related miRNAs remains ambiguous. In this study, 39 necroptosis-related miRNAs (NRMs) were extracted and 17 differentially expressed NRMs between normal and tumor samples were identified using data form The Cancer Genome Atlas (TCGA). After applying univariate Cox proportional hazard regression analysis and LASSO Cox regression model, six necroptosis-related miRNA signatures were identified in the training cohort and their expression levels were verified by qRT-PCR. Using the expression levels of these miRNAs, all patients were divided into the high- and low-risk groups. Patients in the high-risk group showed poor overall survival (P < 0.0001). Time-dependent ROC curves confirmed the good performance of our signature. The results were verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression models demonstrated that the risk score was an independent prognostic factor. Additionally, a predictive nomogram with good performance was constructed to enhance the implementation of the constructed signature in a clinical setting. We then employed miRBD, miRTarBase, and TargetScan to predict the target genes of six necroptosis-related miRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that 392 potential target genes were enriched in cell proliferation-related biological processes. Six miRNAs and 59 differentially expressed target genes were used to construct an miRNA-mRNA interaction network, and 11 hub genes were selected for survival and tumor infiltration analysis. Drug sensitivity analysis revealed potential drugs that may contribute to cancer management. Hence, necroptosis-related genes play an important role in cancer biology. We developed, for the first time, a necroptosis-related miRNA signature to predict ccRCC prognosis.

Astrocytes promote the proliferation of oligodendrocyte precursor cells through connexin 47-mediated LAMB2 secretion in exosomes.

BACKGROUND: Oligodendrocyte precursor cells (OPCs) can proliferate and differentiate into oligodendrocytes, the only myelin-forming cells in the central nervous system. Proliferating OPCs promotes remyelination in neurodegenerative diseases. Astrocytes (ASTs) are the most widespread cells in the brain and play a beneficial role in the proliferation of OPCs. Connexin 47 (Cx47) is the main component of AST-OPC gap junctions to regulate OPC proliferation. Nonetheless, the specific mechanism remains unclear. METHODS AND RESULTS: This study investigates the proliferation mechanism of OPCs connected to ASTs via Cx47. Cx47 siRNA significantly inhibited OPCs from entering the proliferation cycle. Transcriptome sequencing of OPCs and gene ontology enrichment analysis revealed that ASTs enhanced the exosome secretion by OPCs via Cx47. Transmission electron microscopy, Western blot, and nanoparticle tracking analysis indicated that the OPC proliferation was related to extracellular exosomes. Cx47 siRNA decreased the OPC proliferation and exosome secretion in AST-OPC cocultures. Exogenous exosome supplementation alleviated the inhibitory effect of Cx47 siRNA and significantly improved OPC proliferation. Mass spectrometry revealed that LAMB2 was abundant in exosomes. The administration of exogenous LAMB2 induced DNA replication in the S phase in OPCs by activating cyclin D1. CONCLUSIONS: Collectively, ASTs induce the secretion of exosomes that carry LAMB2 by OPCs via Cx47 to upregulate cyclin D1 thereby accelerating OPC proliferation.

MicroRNA-561-5p Inhibits Cell Proliferation and Invasion by Targeting RAC1 in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: This study aims to investigate how miR-561-5p regulated the expression of RAC1 and whether its effects on RAC1 was associated with the proliferation, migration, invasion, and apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells. MATERIALS AND METHODS: RT-qPCR was performed to assess miR-561-5p expression in human PDAC tissues. A series of in vitro experiments including cell counting Kit-8, colony formation, cell migration and invasion, and apoptosis assays were used to assess the PDAC cell biological behaviors. TargetScan v7.2 was used to identify the miR-561-5p target genes, dual-luciferase reporter assay was performed to confirm the targeted relationship between miR-561-5p and Rac family small GTPase 1 (RAC1). Also, RAC1 was upregulated in miR561-5p overexpressed PDAC cells to evaluate the functional involvement of RAC1 in miR-561-5p mediated PDAC cell proliferation and invasion. RESULTS: The results demonstrated that miR-561-5p expression was lower in PDAC tissues compared with in normal tissues. Overexpression of miR-561-5p inhibited PDAC cell proliferation, migration, and invasion, and promoted apoptosis in vitro, while miR-561-5p-knockdown had the opposite effects in the PDAC cell line BxPC3. Using bioinformatics analysis and dual-luciferase reporter assays, the present study revealed that RAC1 was a direct target of miR-561-5p and that RAC1 overexpression could partly rescue the suppressive effects of miR-561-5p mimics on PDAC cells. CONCLUSION: The overexpression of miR-561-5p may suppress carcinogenesis in PDAC cells by targeting RAC1 and inhibit PDAC cell proliferation and invasion.

Developments in the Antitumor Activity, Mechanisms of Action, Structural Modifications, and Structure-Activity Relationships of Steroidal Saponins.

Steroidal saponins, a class of natural products formed by the combination of spirosteranes with sugars, are widely distributed in plants and have various biological activities, such as antitumor, anti-inflammatory, anti-bacterial, anti-Alzheimer's, anti-oxidation, etc. Particularly, extensive research on the antitumor property of steroidal saponins has been conducted. Steroidal sapogenins, the aglycones of steroidal saponins, also have attracted much attention due to a vast range of pharmacological activities similar to steroidal saponins. In the past few years, structural modifications on the aglycones and sugar chains of steroidal saponins have been carried out and some achievements have been made. In this mini-review, the antitumor activity, action mechanisms, and structural modifications, along with the structure-activity relationships of steroidal saponins and their derivatives, are summarized.

Swine wastewater treatment by combined process of iron carbon microelectrolysis-physical adsorption-microalgae cultivation.

Combined treatments were designed based on iron-carbon micro-electrolysis treatment (ICME), physical adsorption (PA) with zeolite (Z) or vermiculite (V) and microalgae cultivation (MC, Chlorella vulgaris) for removing pollutants from swine wastewater (SW): ICME + MC (IM), ICME + Z + MC (IZM) and ICME + V + MC (IVM). Results showed that the minimum total nitrogen (TN) of 43.66 mg L-1, NH4+-N of 1.33 mg-1 and total phosphorus (TP) of 0.14 mg-1 were obtained by IVM, while the minimum chemical oxygen demand (COD) was 105 mg-1 via IM. During the process of combined treatments, ICME contributed most to the removal of TN (84.52% by IZM), TP (97.78% by IVM and IZM) and COD (62.44% by IVM), and maximum NH4+-N removal (55.64%) was obtained by MC procedure in IM process. Vermiculite performed better than zeolite during all the combined treatments. Besides, the maximum cell dry weight (CDW, 0.74 g-1) of C. vulgaris was obtained by IM on day 13. The results provide an efficient integrated method for swine wastewater treatment.

Public transcriptome database-based selection and validation of reliable reference genes for breast cancer research.

BACKGROUND: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is the most sensitive technique for evaluating gene expression levels. Choosing appropriate reference genes (RGs) is critical for normalizing and evaluating changes in the expression of target genes. However, uniform and reliable RGs for breast cancer research have not been identified, limiting the value of target gene expression studies. Here, we aimed to identify reliable and accurate RGs for breast cancer tissues and cell lines using the RNA-seq dataset. METHODS: First, we compiled the transcriptome profiling data from the TCGA database involving 1217 samples to identify novel RGs. Next, ten genes with relatively stable expression levels were chosen as novel candidate RGs, together with six conventional RGs. To determine and validate the optimal RGs we performed qRT-PCR experiments on 87 samples from 11 types of surgically excised breast tumor specimens (n = 66) and seven breast cancer cell lines (n = 21). Five publicly available algorithms (geNorm, NormFinder, ΔCt method, BestKeeper, and ComprFinder) were used to assess the expression stability of each RG across all breast cancer tissues and cell lines. RESULTS: Our results show that RG combinations SF1 + TRA2B + THRAP3 and THRAP3 + RHOA + QRICH1 showed stable expression in breast cancer tissues and cell lines, respectively, and that they displayed good interchangeability. We propose that these combinations are optimal triplet RGs for breast cancer research. CONCLUSIONS: In summary, we identified novel and reliable RG combinations for breast cancer research based on a public RNA-seq dataset. Our results lay a solid foundation for the accurate normalization of qRT-PCR results across different breast cancer tissues and cells.

Experimental and clinical evidence suggests that GRPEL2 plays an oncogenic role in HCC development.

Hepatocellular carcinoma (HCC) continues to cause severe burden worldwide. The limited options especially toward HCC with metastasis prompts us to identify novel molecules for either diagnostic/prognostic or therapeutic purposes. GRPEL2 is well defined in maintaining mitochondrial homeostasis, which is critical to multiple biological processes for cancer survival. However, its role in HCC progression was not investigated before. In our analysis using data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) dataset and tissue microarray, higher expression levels of GRPEL2 were obseved in HCC tissues compared to in normal liver tissues, and indicated higher tumor grade, higher tumor stage, and shorter overall survival (OS). Consistent with the results of above analyses, the functional experiments validated that GRPEL2 acted as a tumor-promoting factor in HCC progression. GRPEL2 knockdown suppressed cell growth, migration, and invasion in vitro, as well as inhibited tumor growth in vivo. Moreover, GRPEL2 deficiency also accelerated reactive oxygen species (ROS) production and increased mitochondrial membrane potential (MMP), leading to cell apoptosis. In addition, we found that the cell cycle and NF-κB signaling pathways were responsible for GRPEL2-induced HCC progression, based on the results of Gene Set Enrichment Analysis (GSEA) and subsequent experimental validation. Our study, for the first time, identified the role of GRPEL2 in HCC development and provided a compelling biomarker for targted therapy in HCC treatment.

[Extraction and separation, structure analysis and biological activity of polysaccharides from Atractylodis Rhizoma].

Atractylodis Rhizoma(AR) is a traditional Chinese medicinal material for food and medicine, with the functions of eli-minating dampness, strengthening the spleen, expelling wind evil and dispersing cold. AR contains a variety of compounds, including sesquiterpenoids, alkynes, triterpenoids, aromatic glycosides, polysaccharides and so on. At present, the researches on AR mainly focus on volatile components, with relatively fewer researches on non-volatile components. Polysaccharide from Atractylodis Rhizoma(ARP) is an important material basis among non-volatile components for the efficacy. Due to its many biological activities such as immunomodulatory activity, anti-tumors, anti-virus and anti-oxidation, ARP has certain research value and potential. The diversity of the polysaccharide structure is the basis for biological functions, but it also increases the difficulty of carbohydrate research. The research on the extraction, separation, purification, structure and activity of ARP is in the preliminary exploration stage, still with many shortcomings. Herein, recent advancements in the extraction, purification, structural characteristics and biological activities of ARP were summarized in this article to provide scientific reference for the in-depth systematic research of ARP and the development of AR resources.

A field trials-based authentication study of conventionally and organically grown Chinese yams using light stable isotopes and multi-elemental analysis combined with machine learning algorithms.

In this study, stable isotopes and multi-element signatures combined with chemometrics were used to distinguish conventional and organic Chinese yams based on field trials. Four light stable isotopes δD, δ13C, δ15N, δ18O, and 20 elements (e.g. Li, Na, Mn) were determined, then evaluated using significance analysis and correlation analysis, and modeling of various chemometrics methods. Consequently, the RandomForest model showed the best performance with AUC value of 0.972 and predictive accuracy of 97.3%, and Mn, Cr, Se, Na, δD, As, and δ15N were screened as significant variables. Moreover, many chemical components and antioxidant activity of yam samples were determined spectrophotometrically. The results indicated that organic yams had advantages in secondary metabolites such as polyphenol, flavonoid and saponin; conversely, conventional samples had more primary metabolites like protein and amino acids. Above all, this work provides a beneficial case in the authentication and quality evaluation of conventional and organic yams.

Design, Synthesis and Anti-Tumor Activity of Novel Benzimidazole-Chalcone Hybrids as Non-Intercalative Topoisomerase II Catalytic Inhibitors.

Chemical diversification of type II topoisomerase (Topo II) inhibitors remains indispensable to extend their anti-tumor therapeutic values which are limited by their side effects. Herein, we designed and synthesized a novel series of benzimidazole-chalcone hybrids (BCHs). These BCHs showed good inhibitory effect in the Topo II mediated DNA relaxation assay and anti-proliferative effect in 4 tumor cell lines. 4d and 4n were the most potent, with IC50 values less than 5 µM, superior to etoposide. Mechanistic studies indicated that the BCHs functioned as non-intercalative Topo II catalytic inhibitors. Moreover, 4d and 4n demonstrated versatile properties against tumors, including inhibition on the colony formation and cell migration, and promotion of apoptosis of A549 cells. The structure-activity relationship and molecular docking analysis suggested possible contribution of the chalcone motif to the Topo II inhibitory and anti-proliferative potency. These results indicated that 4d and 4n could be promising lead compounds for further anti-tumor drug research.

Characterization of microRNA profile in IgE-mediated mouse BMMCs degranulation.

BACKGROUND: Mast cells play a central role in innate and adaptive immunity by releasing pre-formed and de novo synthesized mediators, which include microRNAs. Although miRNAs have been confirmed to function in cell proliferation, differentiation, apoptosis, and the immune response, their functions are still limited in mast cells degranulation. METHODS: Here, we survey miRNA expression profiles in activated mouse bone marrow-derived mast cells (BMMCs) with a miRNA microarray and compare the profiles to those from resting BMMCs. Partial miRNAs were selected for confirmation by qPCR, and let-7i was selected for function discover in mast cell degranulation process. TargetScan Mouse database were used for target genes prediction, gene ontology (GO) were used for gene molecular function classifications, and Cytoscape software were used to construct gene network of degranulation. RESULTS: We found 13 up-regulated miRNAs and 7 down-regulated miRNAs in DNP activated BMMCs by miRNA microarray; and let-7b, let-7c, let-7d, let-7f, let-7i, and miR-652 were up-regulated, and miR-296-3p was down-regulated in DNP-stimulated BMMCs by qPCR. In the function research, let-7i can inhibit mast cell degranulation by suppress Exco8 expression. Overall, the data indicate that miRNAs participate in mast cell activation, especial for mast cell degranulation process.

Protective effects of Salidroside on spermatogenesis in streptozotocin induced type-1 diabetic male mice by inhibiting oxidative stress mediated blood-testis barrier damage.

Spermatogenic dysfunction is one of the major secondary complications of male diabetes. Salidroside (SAL) is the important active ingredients isolated from Herba Cistanche, which exhibits numerous pharmacological activities such as antioxidant, anti-diabetic, and anti-inflammatory effects. The present study was designed to determine whether SAL contributes to the recovery from spermatogenic dysfunction in streptozotocin (STZ) induced type-1 diabetic mice. SAL (25, 50, or 100 mg/kg) and Clomiphene citrate (CC, 5 mg/kg) were orally administered to male type-1 diabetic mice for 10 weeks. Testis tissues were collected for histopathological and biochemical analysis. Moreover, reproductive organ weight, sperm parameters, and testicular cell DNA damage were estimated. The results revealed that SAL significantly improved the weight of the reproductive organs, sperm parameters and testicular morphology to different degrees in type-1 diabetic mice. Furthermore, reactive oxygen species (ROS) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), markedly increased in the testicular tissue after SAL treatment. In addition, our data also showed a marked downregulation the fluorescence expressions of p38 MAPK phosphorylation and upregulation the protein expressions of ZO-1, Occludin, Claudin-11 and N-cadherin after SAL administration (100 mg/kg) compared with the type-1 diabetic group. In conclusion, these results demonstrated that SAL exerts protective effects on type-1 diabetes-induced male spermatogenic dysfunction, which is likely mediated by inhibiting oxidative stress-mediated blood testis barrier damage.