Ethnobotanical study on edible flowers in Xishuangbanna, China.

BACKGROUND: Edible flowers (EFs) represent valuable sources of both food and medicinal resources, holding the promise to enhance human well-being. Unfortunately, their significance is often overlooked. Ethnobotanical studies on the EFs are lacking in comparison with their botanical and phytochemical research. The practice of consuming flowers as food has a rich culture and long history in China, especially among different linguistic groups in Xishuangbanna, Yunnan. However, economic activities have led to a decline of this tradition. Consequently, preserving the traditional knowledge and culture tied to the EFs in Xishuangbanna becomes both essential and pressing. METHODS: The field ethnobotanical survey was conducted in Xishuangbanna during five visits in April 2021 and May 2023, covering 48 villages and 19 local markets of all three county-level areas and 9 different linguistic groups. By conducting a comprehensive literature review and on-site field surveys, relevant information regarding the EFs of Xishuangbanna was systematically collected and documented. Additionally, the relative frequency of citation (RFC) values were calculated from the survey data. RESULTS: A total of 212 taxa (including species and varieties) of EFs from 58 families and 141 genera were documented in the study area. The edible parts of flowers were classified into 13 categories including peduncle, petal, flower buds, inflorescence as a whole, and etc. They were consumed in 21 ways and as 8 types of food. The inflorescence was the most commonly consumed category, accounting for 85 species (40.1%) of the total categories. They always eat flowers as vegetables (184 species, 86.8%). The preparing form of stir-frying was the preferred food preparation method (138, 65.1%). The Xishuangbanna locals had profound knowledge of which EFs required specific processing to remove their toxicity or bitterness. The dishes can be made from either exclusively from the flowers themselves or by incorporating them alongside other plant parts like stems and leaves. Some EFs with high RFC value, such as Musa acuminata and Bauhinia variegata var. candida, showed significant cultural meanings. These edible flowers occupy specific positions in local traditional culture. CONCLUSION: Traditional knowledge regarding edible flowers holds substantial significance and serves as a representative element of the flower-eating culture in Xishuangbanna. Nevertheless, this knowledge and cultural practice are currently decreasing. Serving as a bridge between tradition and modernity, the flower-eating culture, which derives from local people's practical experience, shows the potential of EFs and can be applied to the conservation of biocultural diversity, healthy food systems, and sustainable development.

Circular RNA circTRAPPC6B Enhances IL-6 and IL-1ß Expression and Repolarizes Mycobacteria Induced Macrophages from M2- to M1-Like Phenotype by Targeting miR-892c-3p.

Mycobacterium tuberculosis (Mtb) infection elicits macrophage polarization into M2 phenotype to block the host's protective immune response. However, it remains unclear how Mtb regulates macrophage polarization. Recent studies have suggested that noncoding RNA may play a role in macrophage polarization. In this study, we investigated the potential involvement of circTRAPPC6B, a circular RNA that is downregulated in tuberculosis (TB) patients, in regulating macrophage polarization. We found that Mtb infection downregulated M1-related IL-6 and IL-1ß while highly expressed M2-related CCL22 and CD163. Overexpressed circTRAPPC6B had switched Mtb-infected macrophages from M2- to M1-like phenotype, accompanied by upregulation of IL-6 and IL-1ß. Meanwhile overexpressed circTRAPPC6B significantly inhibited Mtb growth in macrophages. Our findings suggest that circTRAPPC6B may regulate macrophage polarization by targeting miR-892c-3p, which is highly expressed in TB patients and M2-like macrophages. And miR-892c-3p inhibitor decreased intracellular Mtb growth in macrophages. Thus, TB-inhibited circTRAPPC6B could specifically induce IL-6 and IL-1ß expression to switch/antagonize Mtb-induced macrophage polarization from M2- to M1-like phenotype by targeting miR-892c-3p, leading to enhanced host clearance of Mtb. Our results reveal a potential role for circTRAPPC6B in regulating macrophage polarization during Mtb infection and provide new insights into the molecular mechanisms underlying host defense against Mtb.

Preparation of oral nanoparticles of Perillae Fructus oil and prevention application of cold stress in mice.

Perillae Fructus oil has an important function in relieving cold stress. However, its application in this aspect has still been restricted because of instability and low bioavailability. In this study, Perillae Fructus oil was extracted through Soxhlet extraction, analyzed through gas chromatography-mass spectrometry (GC-MS), and nanopackaged into a yeast shell for the preparation of nanoparticles for oral administration. The characteristics of the nanoparticles were investigated using a Malvern zeta-size nanoinstrument, scanning electron microscopy (SEM), and high-performance liquid chromatography (HPLC). Then, the roles of orally administered nanoparticles in relieving cold stress were evaluated by investigating blood physiological and biochemical indexes in mice. The results showed that the oil yield from Perillae Fructus and shell yield from yeast cells were ~48.37% and ~16.87%, respectively. Approximately 89.21% of the added oil was packaged into the yeast shell to form nanoparticles with an average diameter of 316.74 nm and a surface charge of +2.9 mV. The nanoparticles were stable in simulated gastric acid and could be effectively released in simulated intestinal fluid with an efficiency of ~91.34%. After oral administration of nanoparticles, the mouse blood indexes of white blood cells (WBCs), superoxide dismutase (SOD) activity, and malonaldehyde (MDA) content were recovered compared to those in model mice, with a more remarkable effect than oral administration of free Perillae Fructus oil. Overall, the stability and bioavailability were improved by packaging Perillae Fructus oil into a yeast shell. These nanoparticles are a new agent for the prevention of cold stress.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Cytotoxic cycloartane triterpenoid saponins from Actaea vaginata and their mechanism of action.

A further phytochemical investigation of the whole plants of Actaea vaginata afforded two new cycloartane triterpenoid saponins, (20S*,24R*)-15α,16ß-diacetoxy-20,24-epoxy-9,19-cyclolanostane-3ß,25-diol-3-O-ß-d-xylopyranoside (1) and (20S)-15ß,16ß -diacetoxy-18,20-epoxy-3ß,25-diol-24-oxo-9,19-cyclolanostan-3-O-ß-D-xylo-pyrano-syl-25-O-ß-d-glucopyranoside (2), together with four known compounds (3-6). Their structures were established on the basis of extensive analysis of NMR and HRESIMS data as well as by comparison with the reported data in the literature. All the isolates were evaluated for their cytotoxic activities against human hepatocellular carcinoma HepG2 cell line. Compounds 1 and 2 exhibited weak cytotoxicity with IC50 values of 36.10 and 27.39 µM, respectively. In addition, beesioside I (6) was found to significantly inhibit proliferation and induce apoptosis in HepG2 cells. A closer examination of underlying mechanism revealed that beesioside I could increase the levels of ROS and caspase-3 and promote phosphorylation of JNK in the JNK signaling pathway. Molecular modeling studies also shed further light on how beesioside I interacted with the key protein kinase.

Soulieoside U, a new cycloartane triterpene glycoside from Actaea vaginata.

One new cycloartane triterpene bisdesmoside, soulieoside U, was isolated from the rhizomes of Actaea vaginata. Its structure was elucidated by extensive analysis of the NMR and MS data. Soulieoside U was evaluated for cytotoxic activities against three human cancer cell lines.

Epidemiological and clinical characteristics of respiratory viruses in 4403 pediatric patients from multiple hospitals in Guangdong, China.

BACKGROUND: Acute respiratory infections (ARI) cause considerable morbidity and mortality worldwide, especially in children. Unfortunately, there are limited multi-center data on common viral respiratory infections in south China. METHODS: A total of 4403 nasal swabs were collected from children in 10 cities in Guangdong, China in 2019. Seven respiratory viruses, influenza A virus (IFA), influenza B virus (IFB), respiratory syncytial virus (RSV), adenoviruses (ADV) and parainfluenza virus types 1-3 (PIV1, PIV2 and PIV3), were detected by direct immunofluorescence antibody assay. The personal information and clinical characteristics were recorded and analyzed. RESULTS: The results showed that at least one virus was detected in 1099 (24.96 %) samples. The detection rates of RSV, IFA, ADV, PIV3, PIV1 and PIV2 were 7.13 % (314/4403), 5.31 % (234/4403), 4.02 % (177/4403), 3.04 % (134/4403), 1.70 % (75/4403) and 1.16 % (51/4403), respectively. The detection rate of RSV was highest in 0-6-month-old children at 18.18 % (106/583), while the detection rate of IFA was highest in 12-18-year-old children at 20.48 % (17/83). The total detection rates in winter and spring were 35.67 % (219/614) and 34.56 % (403/1166), higher than those in summer, 17.41 % (284/1631), and autumn, 19.46 % (193/992). CONCLUSIONS: RSV and IFA were the main respiratory viruses in children. With increasing age the detection rate of RSV decreased in children, but the trends for the detection rates of IFA and IFB were the opposite. This study provided the viral etiology and epidemiology of pediatric patients with ARI in Guangdong, China.

Circular RNA TRAPPC6B inhibits intracellular Mycobacterium tuberculosis growth while inducing autophagy in macrophages by targeting microRNA-874-3p.

OBJECTIVES: Genetic and epigenetic mechanisms regulate antimicrobial immunity against Mycobacterium tuberculosis (Mtb) infection. METHODS: The present study assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms wherein circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages. RESULTS: The Mtb infection of monocytes/macrophages resulted in a significantly decreased level of circTRAPPC6B that inhibited intracellular Mtb growth in macrophages. Conversely, circTRAPPC6B expression enhanced autophagy or autophagy-associated protein LC3-II production in Mtb-infected macrophages. circTRAPPC6B-enhanced autophagy aggregation or sequestration was also observed in fluorescence in situ hybridisation (FISH) analysis and confocal imaging. Mechanistically, circTRAPPC6B targets an inhibiting element miR-874-3p, as shown by bioinformatics, dual-luciferase reporter gene analysis and pull-down assay, respectively. Notably, miR-874-3p prohibited autophagy via suppressing autophagy protein ATG16L1 by binding to its 3'-untranslated region (UTR) in Mtb-infected macrophages and thus promoting intracellular Mtb growth. Concurrently, circTRAPPC6B enhanced autophagy in Mtb-infected macrophages by blocking the ability of miR-874-3p to inhibit ATG16L1. Thus, circTRAPPC6B antagonises the ability of miR-874-3p to suppress ATG16L1 expression and activate and enhance autophagy sequestration to restrict Mtb growth in macrophages. CONCLUSION: The current findings suggested that both circTRAPPC6B and miR-874-3p mechanisms can be explored as potential therapeutics against Mtb infection.

Insights into triterpene synthesis and unsaturated fatty-acid accumulation provided by chromosomal-level genome analysis of Akebia trifoliata subsp. australis.

Akebia trifoliata subsp. australis is a well-known medicinal and potential woody oil plant in China. The limited genetic information available for A. trifoliata subsp. australis has hindered its exploitation. Here, a high-quality chromosome-level genome sequence of A. trifoliata subsp. australis is reported. The de novo genome assembly of 682.14 Mb was generated with a scaffold N50 of 43.11 Mb. The genome includes 25,598 protein-coding genes, and 71.18% (485.55 Mb) of the assembled sequences were identified as repetitive sequences. An ongoing massive burst of long terminal repeat (LTR) insertions, which occurred ~1.0 million years ago, has contributed a large proportion of LTRs in the genome of A. trifoliata subsp. australis. Phylogenetic analysis shows that A. trifoliata subsp. australis is closely related to Aquilegia coerulea and forms a clade with Papaver somniferum and Nelumbo nucifera, which supports the well-established hypothesis of a close relationship between basal eudicot species. The expansion of UDP-glucoronosyl and UDP-glucosyl transferase gene families and ß-amyrin synthase-like genes and the exclusive contraction of terpene synthase gene families may be responsible for the abundant oleanane-type triterpenoids in A. trifoliata subsp. australis. Furthermore, the acyl-ACP desaturase gene family, including 12 stearoyl-acyl-carrier protein desaturase (SAD) genes, has expanded exclusively. A combined transcriptome and fatty-acid analysis of seeds at five developmental stages revealed that homologs of SADs, acyl-lipid desaturase omega fatty acid desaturases (FADs), and oleosins were highly expressed, consistent with the rapid increase in the content of fatty acids, especially unsaturated fatty acids. The genomic sequences of A. trifoliata subsp. australis will be a valuable resource for comparative genomic analyses and molecular breeding.

iTRAQ­based proteomic analysis reveals potential regulatory networks in dust mite­related asthma treated with subcutaneous allergen immunotherapy.

Asthma is one of the most common childhood chronic diseases worldwide. Subcutaneous immunotherapy (SCIT) is commonly used in the treatment of house dust mite (HDM)­related asthma in children. However, the therapeutic mechanism of SCIT in asthma remains unclear. The present study aimed to investigate the molecular biomarkers associated with HDM­related asthma in asthmatic children prior and subsequent to SCIT treatment compared with those in healthy children via proteomic analysis. The study included a control group (30 healthy children), ­Treatment group (30 children with HDM­related allergic asthma) and +Treatment group (30 children with HDM­related allergic asthma treated with SCIT). An isobaric labeling with relative and absolute quantification­based method was used to analyze serum proteome changes to detect differentially expressed proteins, while functional enrichment and protein­protein interaction network analysis were used to select candidate biomarkers. A total of 72 differentially expressed proteins were detected in the ­Treatment, +Treatment and control groups. A total of 33 and 57 differentially expressed proteins were observed in the ­Treatment vs. control and +Treatment vs. control groups, respectively. Through bioinformatics analysis, 5 candidate proteins [keratin 1 (KRT1), apolipoprotein B (APOB), fibronectin 1, antithrombin III (SERPINC1) and α­1­antitrypsin (SERPINA1)] were selected for validation by western blotting; among them, 4 proteins (KRT1, APOB, SERPINC1 and SERPINA1) showed robust reproducibility in asthma and control samples. This study illustrated the changes in proteome regulation following SCIT treatment for asthma. The 4 identified proteins may serve as potential biomarkers prior and subsequent to SCIT treatment, and help elucidate the molecular regulation mechanisms of SCIT to treat HDM­related asthma.

Elevation in the counts of IL-35-producing B cells infiltrating into lung tissue in mycobacterial infection is associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.

IL-35 is an anti-inflammatory cytokine and is thought to be produced by regulatory T (Treg) cells. A previous study found that IL-35 was upregulated in the serum of patients with active tuberculosis (ATB), and IL-35-producing B cells infiltrated to tuberculous granuloma of patients with ATB. Purified B cells from such patients generated more IL-35 after stimulation by antigens of Mycobacterium tuberculosis and secreted more IL-10. However, the function and the underlying mechanisms of IL-35-producing B cells in TB progression have not been investigated. The present study found that the expression of mRNA of IL-35 subsets Ebi3 and p35 was elevated in mononuclear cells from peripheral blood, spleen, bone marrow, and lung tissue in a mouse model infected with Mycobacterium bovis BCG, as tested by real-time polymerase chain reaction. Accordingly, the flow cytometry analysis showed that the counts of a subset of IL-35+ B cells were elevated in the circulating blood and in the spleen, bone marrow, and lung tissue in BCG-infected mice, whereas anti-TB therapy reduced IL-35-producing B cells. Interestingly, BCG infection could drive the infiltration of IL-35-producing B cells into the lung tissue, and the elevated counts of IL-35-producing B cells positively correlated with the bacterial load in the lungs. Importantly, the injection of exogenous IL-35 stimulated the elevation in the counts of IL-35-producing B cells and was associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.The study showed that a subset of IL-35-producing B cells might take part in the downregulation of immune response in mycobacterial infection.

PEGylated WS2 nanodrug system with erythrocyte membrane coating for chemo/photothermal therapy of cervical cancer.

The side effects of chemical drugs and multi-drug resistance are serious obstacles hindering efficient tumor therapy. Therefore, recently, the combination of chemo/photothermal therapy (CT/PT) has been adopted to address these issues using a low drug dosage. However, the development of multi-functional drug delivery systems with improved immune escape capability and enhanced drug accumulation at specific tumor tissues is still in its infancy. Herein, polyethylene glycol (PEG)-modified WS2 nanosheets (WS2-PEG) were used as a nanocarrier scaffold for doxorubicin (DOX, D) loading and near-infrared fluorescence probe indocyanine green (ICG, I) doping. After surface modification with the erythrocyte membrane (M) and targeted folic acid (FA) molecule, a new biomimetic system (WID@M-FA NPs) with high biocompatibility, prolonged cycle time (3.6-fold longer than WID NPs) and remarkable near-infrared photothermal function was developed for a targeted cervical cancer therapy. The in vitro assay indicated that the photothermal effects caused by ICG upon laser irradiation not only enhanced the cellular uptake of the drug, but also enhanced its tumor cell killing efficiency. Moreover, the targeted accumulation of DOX at the cervical cancer tissue and the synergistic chemo/photothermal therapy finally resulted in tumor elimination to more than 95% without side effects to the normal tissues in vivo. Thus, these excellent preclinical results indicate that WID@M-FA NPs may be an efficient therapeutic modality for the treatment of cervical cancer.

Study of Circulating Natural Antibodies Against CD25 and FOXP3 in Type-2 Diabetes.

BACKGROUND: Natural antibodies are critical components for maintaining homeostasis of the immune system. Regulatory T (Treg) cells have indispensable effects on immunosuppressive function and peripheral immune tolerance. Both CD25 and FOXP3 are specifically expressed in Treg cells and their natural antibodies may protect against the development of type-2 diabetes (T2D). The present study aimed to test whether circulating antibodies against CD25 and FOXP3 were altered in first-episode patients with T2D. METHODS: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect the levels of plasma IgG antibodies against five linear peptide antigens with three derived from CD25 (named CD25a, CD25b, CD25c) and two derived from FOXP3 (called FOXP3a and FOXP3b) among 200 first-episode patients with T2D and 220 healthy controls. RESULTS: Mann-Whitney U test showed a significant decrease in anti-CD25a IgG levels in patients with T2D as compared with the healthy controls (Z = -3.438, p = 0.0006), male patients mainly contributing to the decreased levels of anti-CD25a IgG levels (Z = -3.065, p = 0.002). The other four IgG tests demonstrated a lower level of plas-ma IgG antibodies in the patient group than the control group, but failed to show statistical significance (p > 0.01). ROC curve analysis indicated that the anti-CD25a IgG assay had the best sensitivity of 19.5% against the specificity of 90%. CONCLUSIONS: Decreased anti-CD25 IgG levels in the circulation may represent a reduction in the number of Treg cells and detection of such antibodies may be beneficial to the understanding of immunological changes in T2D patients.

miR-155 increases stemness and decitabine resistance in triple-negative breast cancer cells by inhibiting TSPAN5.

Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24- CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24- CD44+ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC.

mTOR Signaling Upregulates CDC6 via Suppressing miR-3178 and Promotes the Loading of DNA Replication Helicase.

mTOR signaling pathway is deregulated in most cancers and uncontrolled cell cycle progression is a hallmark of cancer cell. However, the precise molecular mechanisms of the regulation of DNA replication and chromatin metabolism by mTOR signaling are largely unknown. We herein report that mTOR signaling promotes the loading of MCM2-7 helicase onto chromatin and upregulates DNA replication licensing factor CDC6. Pharmacological inhibition of mTOR kinase resulted in CHK1 checkpoint activation and decreased MCM2-7 replication helicase and PCNA associated with chromatins. Further pharmacological and genetic studies demonstrated CDC6 is positively controlled by mTORC1-S6K1 and mTORC2 signaling. miRNA screening revealed mTOR signaling suppresses miR-3178 thereby upregulating CDC6. Analysis of TCGA data found that CDC6 is overexpressed in most cancers and associates with the poor survival of cancer patients. Our findings suggest that mTOR signaling may control DNA replication origin licensing and replisome stability thereby cell cycle progression through CDC6 regulation.

MTB driven B cells producing IL-35 and secreting high level of IL-10 in the patients with active pulmonary tuberculosis.

Regulatory B cells (Bregs) have critical roles as a negative regulator of immunity, mainly due to the fact that it secrets high a level of interleukin 10 (IL-10). Recently, a new subset of Bregs was identified as a key source of IL-35, which is an immunosuppressive cytokine and conventionally thought to be secreted by regulatory T cells (Tregs). Our previous study showed that the level of IL-35 in serum was elevated in the patients with active tuberculosis (ATB). However, none of the studies reported that IL-35 is secreted by B cells in ATB patients. In the current study, we found that the mRNA expressions of the both subunits (p35 and Ebi3) of IL-35 by circulating B cells were increased in ATB patients. By using immunohistochemistry and immunofluorescence staining, we found a subset of B cells infiltrated into the tuberculous granuloma of ATB patients also expressed IL-35. Moreover, Mycobacterium tuberculosis (MTB) lysate stimulation assay also demonstrated higher levels of IL-35 were exerted by MTB lysate within purified B cells from healthy control group (HC). Flow cytometry analysis further showed that the IL-35-producing B cells from ATB patients produced a higher level of IL-10. Taken together, IL-35-producing B cells may play a regulatory role during MTB infection by producing IL-10.

Effects of exogenous IL-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T cells.

BACKGROUND: This study aims to investigate the effects of exogenous interleukin (IL)-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T (Treg) cells. METHODS: After isolating the CD4+ CD25+ Treg cells from the peripheral blood, flow cytometry was used to detect the purity of the Treg cells. A549 cells were divided into blank (no transfection), empty plasmid (transfection with pIRES2-EGFP empty plasmid) or IL-37 group (transfection with pIRES2-EGFP-IL-37 plasmid). RT-PCR was used to detect mRNA expression of IL-37 and ELISA to determine IL-37 and MMP-9 expressions. Western blotting was applied to detect the protein expressions of PCNA, Ki-67, Cyclin D1, CDK4, cleaved caspase-3 and cleaved caspase-9. MTT assay, flow cytometry, scratch test and transwell assay were performed to detect cell proliferation, cycle, apoptosis, migration and invasion. Effect of exogenous IL-37 on the chemotaxis of Treg cells was measured through transwell assay. Xenograft models in nude mice were eastablished to detect the impact of IL-37 on A549 cells. RESULTS: The IL-37 group had a higher IL-37 expression, cell apoptosis in the early stage and percentage of cells in the G0/G1 phase than the blank and empty plasmid groups. The IL-37 group had a lower MMP-9 expression, optical density (OD), percentage of cells in the S and G2/M phases, migration, invasion and chemotaxis of CD4+CD25+ Foxp3+ Treg cells. The xenograft volume and weight of nude mice in the IL-37 group were lower than those in the blank and empty plasmid groups. Compared with the blank and empty plasmid groups, the IL-37 group had significantly reduced expression of PCNA, Ki-67, Cyclin D1 and CDK4 but elevated expression of cleaved caspase-3 and cleaved caspase-9. CONCLUSION: Therefore, exogenous IL-37 inhibits the proliferation, migration and invasion of human lung adenocarcinoma A549 cells as well as the chemotaxis of Treg cells while promoting the apoptosis of A549 cells.

Antihyperglycemic and antioxidant effect of the total flavones of Potentilla kleiniana Wight et Arn. in streptozotocin induced diabetic rats.

To investigate the antihyperglycemic and antioxidant activity of the total flavones of Potentilla kleiniana Wight et Arn. (TFP) in streptozotocin (STZ) induced diabetic rats. STZ-induced diabetic rats were treated with TFP weekly for 4 weeks at three doses (100 mg/kg, 200 mg/kg and 400 mg/kg). Blood glucose levels (BGL), body weight, insulin, total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), very low density lipoprotein (VLDL), low density lipoprotein (LDL), malondialdehyde (MDA), glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) levels of liver and pancreas were measured weekly for 4 weeks. STZ administration resulted in oxidative damage of pancreas, then hyperglycemia proved by higher MDA, lower insulin and higher BGL in comparison to normal rats. TC, TG, LDL and VLDL cholesterol levels were also significantly elevated with decreased GSH, SOD, and CAT levels. A steady decrease in BGL and increase in insulin level were observed 4 weeks after TFP treatment in a dose dependent manner, as well as remarkable improvement in body weight and biochemical parameters. TFP have the effect of inhibiting hyperglycemia and oxidative stress, and the administration may be helpful in the prevention of diabetic complications associated with oxidative stress.

IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin.

Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

MiR-204, down-regulated in retinoblastoma, regulates proliferation and invasion of human retinoblastoma cells by targeting CyclinD2 and MMP-9.

Aberrant expression of miR-204 had been frequently reported in cancer studies; however, the mechanism of its function in retinoblastoma remained unknown. Here, we reported that miR-204 was frequently downregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-204 inhibited retinoblastoma cells' proliferation and invasion. In vivo study indicated that restoration of miR-204 inhibited tumor growth. CyclinD2 and MMP-9 were identified as potential targets of miR-204. In addition, a reverse correlation between miR-204 and CyclinD2 or MMP-9 expression was noted in retinoblastoma tissues. Taken together, our results identified a crucial tumor suppressive role of miR-204 in the progression of retinoblastoma.