Context Osteoarthritis is a chronic degenerative disease characterized by metabolic dysregulation, inflammation, and oxidative stress. MALAT1 plays a key role in OA pathogenesis. Pae exhibits anti-inflammatory activity, but its regulatory role in cholesterol-oxidative stress-iron metabolism in chondrocytes remains unclear.Objective To investigate whether Pae can alleviate cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes via modulation of MALAT1.Materials & methods OA was induced in mice using a modified Hulth method, followed by intra-articular injection of MALAT1 overexpression plasmid. Cartilage morphology and the expression of MALAT1 and related genes/proteins were assessed by histology, RT-PCR, and Western blot. In vitro, IL-1β-treated chondrocytes were used to model OA, and MALAT1 knockdown was achieved via lentiviral transfection. FISH, RT-PCR, Western blot, and flow cytometry were used to evaluate the effects of Pae on molecular markers and apoptosis.Results In vivo In vivo, Pae improved cartilage morphology and restored the expression of key genes and proteins, whereas MALAT1 overexpression attenuated these effects. In IL-1β-treated OA chondrocytes, Pae reversed abnormal mRNA expression of MALAT1 and related genes. FISH analysis showed that Pae reduced MALAT1 fluorescence in chondrocytes. Western blot revealed that Pae significantly restored protein expression in sh-MALAT1 chondrocytes. Furthermore, flow cytometry analysis revealed that Pae intervention significantly reduced the apoptosis rate of IL-1β-induced chondrocytes from 34.57% to 27.74%. sh-MALAT1 resulted in a more pronounced reduction in chondrocyte apoptosis, with the apoptotic rate further decreasing to 13.21%.Discussion and Conclusion Paeoniflorin ameliorates cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes via modulation of MALAT1, providing mechanistic insight into its potential therapeutic effects.

Gastric cancer remains a leading cause of cancer-related mortality worldwide, characterized by poor prognosis due to its aggressive nature and high metastatic potential. While the E2-conjugating enzyme UBE2I (UBC9), essential for SUMOylation, has been implicated in various cancers, its precise role in gastric cancer remains poorly understood. In the study, we demonstrate significant UBC9 overexpression in gastric cancer tissues, which correlates with poor clinical outcomes. Functional analyses revealed that UBC9 knockdown significantly suppressed gastric cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas UBC9 overexpression enhanced these malignant phenotypes. Through integrated transcriptomic and proteomic analyses, we identified ATF2 (Activating Transcription Factor 2) as a crucial downstream effector of UBC9-mediated oncogenic signaling. The mechanistic relationship between these factors was confirmed as ATF2 knockdown substantially attenuated the oncogenic effects of UBC9 overexpression. This newly identified UBC9-ATF2 regulatory axis promotes gastric cancer progression by enhancing cellular proliferation and metastatic potential. Our findings establish UBC9 and ATF2 as promising prognostic biomarkers and potential therapeutic targets, suggesting that intervention in the UBC9-ATF2 axis may provide novel therapeutic strategies for inhibiting gastric cancer progression and improving patient outcomes.

OBJECTIVES:To investigate the mechanism by which Morinda officinalis polysaccharide (MOP) delays osteoarthritis chondrocyte degeneration. METHODS:In primary cultures of chondrocytes from 4-week-old C57BL/6 mice, the effects of IL-1β and MOP treatment at different concentrations on cell viability were assessed with CCK-8 assay. The treated cells were examined for protein expressions of PKM2, caspase-1, and GSDMD using Western blotting and for XIST expression using fluorescence in situ hybridization (FISH). In IL-1β-induced mouse chondrocytes, the effects of MOP, transfection for XIST overexpression or knockdown, and MOP treatment after the transfection were tested by detecting mRNA levels of GluT1, HK2, PKM2, LDHA, PFKFB3, NLRP3, caspase-1, and GSDMD; flow cytometry, Western blotting, and toluidine blue staining were used to analyze chondrocyte apoptosis, expressions of glycolysis and pyroptosis regulators, and glycosaminoglycan expression. RESULTS:The second-passage chondrocytes showed good viability and positive collagen II staining. IL-1β induction caused degenerative morphological changes of the cells, decreased collagen II expression, and upregulated cellular expressions of PKM2, caspase-1, and GSDMD proteins. MOP treatment (especially at 4 mg/mL) significantly enhanced cell viability and reduced HK2, PKM2, caspase-1 and GSDMD expressions in IL-1β‑induced mouse chondrocytes. XIST was localized predominantly in the nuclei of the chondrocytes, and its expression increased significantly in IL-1β‑treated cells, and was attenuated by MOP treatment. XIST overexpression synergized with IL-1β to upregulate mRNA and protein expressions of glycolysis- and pyroptosis-related factors in the chondrocytes, and such effects were obviously attenuated by MOP. Conversely, XIST knockdown significantly inhibited chondrocyte apoptosis and glycosaminoglycan expression, and down-regulated glycolysis- and pyroptosis-related proteins. MOP treatment exhibited similar protective effects to XIST knockdown, and their combination significantly augmented these protective effects. CONCLUSIONS:MOP mitigates IL-1β‑induced mouse chondrocyte degeneration by modulating glycolysis and pyroptosis via targeting XIST.

Chronic pain represents the prevailing symptom among patients suffering from knee osteoarthritis (KOA). In KOA, peripheral sensitization is driven by disruptions in subchondral bone homeostasis, local inflammatory responses, and variations in neuropeptide and neurotransmitter levels. Calcitonin, a pivotal peptide involved in bone metabolism, additionally exhibits potent analgesic properties. This study aimed to elucidate the mechanisms underlying calcitonin's neuromodulatory effects related to pain in the treatment of KOA. Three experiments were conducted: (1) assessing calcitonin's therapeutic effects via histomorphology, nociceptive behavioral assessments, and Western blot analysis of proteins; (2) verification of the involvement of neurotransmitters and neuropeptides in calcitonin's action using the Signal Transduction PathwayFinder PCR Array, Bio-Plex suspension chip, and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS); and (3) exploration of calcitonin's impact on brain function through functional magnetic resonance imaging (fMRI). Experiment 1 validated calcitonin's efficacy in KOA models. Experiment 2 demonstrated the involvement of the retinoic acid signaling pathway in calcitonin treatment, confirming that its analgesic efficacy is associated with the modulation of neuropeptides and neurotransmitters. Experiment 3 revealed that calcitonin treatment could reverse regional homogeneity and amplitude of low-frequency fluctuations in the hippocampus and tegmental nucleus. The study affirmed the critical role of pain-related neuromodulation mechanisms in calcitonin treatment, demonstrating that its analgesic effects are mediated through the modulation of neurotransmitters, neuropeptides, and brain function, as observed via fMRI. These findings provide a theoretical foundation for the clinical application of calcitonin in the treatment of KOA pain.

From the perspective of circular RNA forkhead box protein O3(circFOXO3)regulating glycolysis in osteoarthritis(OA)chondrocytes,this study investigated the mechanism by which Tougu Xiaotong Capsules(TGXTC)alleviated OA degeneration.In in vivo experiments,after randomized grouping and relevant interventions,morphological staining was used to observe structural changes in cartilage tissue.The mRNA level of circFOXO3 in cartilage tissue was detected by real-time quantitative PCR(RT-qPCR).Western blot analysis was used to detect changes in the expression of glucose transporter 1(GLUT1),hexokinase 2(HK2),pyruvate kinase M2(PKM2),lactate dehydrogenase A(LDHA),and matrix metalloproteinase 13(MMP13).In in vitro experiments,fluorescence in situ hybridization(FISH)was used to detect circFOXO3 expression in chondrocytes from each group.A lentiviral vector was used to construct circFOXO3-silenced(sh-circFOXO3)chondrocytes.RT-qPCR was used to analyze the changes in circFOXO3 levels after silencing,and Western blot was used to assess the regulatory effects of TGXTC on GLUT1,HK2,PKM2,LDHA,and MMP13 proteins in interleukin-1β(IL-1β)-induced chondrocytes under sh-circFOXO3 conditions.Masson staining and alcian blue staining results showed that the cartilage layer structure in the TGXTC and positive drug groups was improved compared with that in the model group.The mRNA level of circFOXO3 was significantly upregulated in both the TGXTC and positive drug groups,while the expression of the above-mentioned proteins was significantly reduced.FISH results showed that TGXTC upregulated the fluorescence intensity of circFOXO3 in IL-1β-induced chondrocytes.In the circFOXO3 silencing experiment,compared with the IL-1βgroup,circFOXO3 levels in the IL-1β+sh-circFOXO3 group were significantly decreased.Compared with the IL-1β+TGXTC group,circFOXO3 levels were significantly reduced in the IL-1β+sh-circFOXO3+TGXTC group.Western blot results indicated that the elevated levels of GLUT1,HK2,PKM2,LDHA,and MMP13 proteins in chondrocytes of the IL-1β group were significantly inhibited by TGXTC intervention.However,this regulatory effect was attenuated after circFOXO3 silencing.In conclusion,TGXTC alleviate glycolytic metabolism disorder in OA chondrocytes and delay OA degeneration by regulating circFOXO3.

LncRNA XIST and Nav1.7 have been identified to be significantly associated with the onset of osteoarthritis. Prim-O-glucosylcimifugin (POG) has antiinflammatory and analgesic effects in treating osteoarthritis (OA). However, its molecular mechanism of action remains unclear. This research investigated whether POG inhibits OA cartilage degeneration by regulating Nav1.7 through lncRNA XIST. We observed the relationship between lncRNA XIST and Nav1.7 through in vivo and in vitro experiments, and utilized lentiviral plasmids for XIST overexpression to further validate the protective effect of POG against OA. In vivo experiments revealed the close association of improving OA cartilage morphological changes by POG with lncRNA XIST and Nav1.7 downregulation and related proteins expression. In vitro experiments demonstrated significantly up-regulated lncRNA XIST and Nav1.7 expression in IL1β-induced chondrocytes, and their levels and related protein expression decreased after POG intervention. FISH indicated that POG attenuated the fluorescence intensity of lncRNA XIST in chondrocytes. RT-PCR and Western blot assays revealed the positive correlation of lncRNA XIST and Nav1.7 expression in chondrocytes. Additionally, flow cytometry results revealed that POG intervention reduced OA chondrocyte apoptosis. Therefore, we conclude that POG can mediate lncRNA XIST to regulate Nav1.7 to delay cartilage degeneration, which is an effective way to treat OA. However, lncRNA XIST is not the only target for regulation, and further discussion is needed.

Gelsemium elegans is a traditional Chinese medicinal plant, with indole alkaloids as its main active ingredient. The plant can be used as medicine, mainly for pain relief, anti-inflammation and anti-tumor. Exogenous stress, such as low temperature, methyl jasmonate (MeJA), and salicylic acid (SA), can affect the growth of G. elegans and the synthesis of secondary metabolites. Under these conditions, there are only a few reports on the selection and validation of internal reference genes in G. elegans. In this study, seven candidate internal reference genes that showed stable expression abundance in the transcriptome database of G. elegans were selected. The stability and reliability of these genes were analyzed in different G. elegans tissues and under low temperature, MeJA, and SA stresses. The results showed that CUL was the optimal reference gene for expression analysis in different G. elegans tissues and under cold stress, SA stress, followed by eEF-1 alpha. Under MeJA stress, the best one was eEF-1 alpha, and the next was CUL. Furthermore, the expression patterns of three different G. elegans genes, including GPPS, ERF, and 60S, were carried out to confirm that single reference gene ( CUL or eEF-1 alpha) or double reference genes ( CUL + eEF-1 alpha) can be selected as the best or perfect combination of reference genes for gene expression analysis in G. elegans. This study lays a foundation for the accurate normalization and quantification of gene expression in G. elegans.

Knee osteoarthritis (KOA) is a chronic degenerative joint disease-causing chronic pain and disability. Neuromodulation of subchondral bone affects KOA-related pain and involves dorsal root ganglion (DRG). Our previous studies have demonstrated efficacy of icariin (ICA) in treating KOA, but neuromodulation mechanisms in peripheral nerves associated with the treatment of chronic pain in KOA remain unclear. This study aimed to investigate peripheral neuromodulation mechanisms of ICA in KOA-related chronic pain: (1) assessing therapeutic effect of ICA in a rat model of KOA-induced chronic pain; (2) investigating changes in pain-related nerve fibres and transient receptor potential vanilloid Subfamily 1 (TRPV1) pathway in subchondral bone following ICA treatment; and (3) exploring expression of pain-related Nogo-A/TRPV1 pathway in DRG, thereby elucidating neurotransmission of pain. Experimental results confirmed the curative effect of ICA on KOA by relieving chronic pain and pathological changes. ICA also effectively reduced bone remodelling, the area of pain-related positive nerve fibres and expression of TRPV1 in subchondral bone. Furthermore, ICA downregulated pain-related Nogo-A/TRPV1 pathway in the DRG. These findings provide new mechanistic insights into the therapeutic potential of ICA in relieving peripheral nervous system-related chronic pain in KOA.

Ethnopharmacological relevance: Bushen Zhuangjin Decoction (BZD) are an herbal compound commonly used to treat osteoarthritis (OA) in China. Aim of the study: This study aimed to verify the mechanism of Bushen Zhuangjin Decoction in relieving the pain of knee osteoarthritis. Materials and methods: Network pharmacology evaluation was used to discover the potential targets of BZD to relieve pain in KOA. The therapeutic effects of BZD treatment on KOA pain using histomorphology, behavioral assessments, suspension chip analysis, and ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) assays. The functional magnetic resonance imaging was used to explore the effects of BZD treatment on brain function associated to KOA. Results: Network pharmacological analysis revealed the association between the analgesic effect of BZD on KOA and the pain signaling neurotransmitter 5-HT. Subsequently, we conducted experiments to verify the therapeutic effect of BZD on pain in KOA animal models. Behavioral tests demonstrated that the pain threshold of knee osteoarthritis rats decreased in PWT and PWL, but BZD was able to increase the pain threshold. Histopathological staining indicated thinning of the cartilage layer and sparse trabeculae in the subchondral bone. Suspension chip analysis revealed a significant increase in pro-inflammatory factors of IL-1 alpha, IL-5, IL-12, IL-17A, RANTES, TNF-alpha and M-CSF in KOA, along with a significant decrease in anti-inflammatory factor of IL-13. However, BZD treatment decreased the expression of pro-inflammatory factors and increased the content of anti-inflammatory factor. UHPLC-MS/MS analysis showed a significant decrease in the serum levels of GABA, E, GSH, Kyn, Met, and VMA in KOA, which were significantly increased by BZD. Conversely, the serum levels of TrpA, TyrA, Spd, and BALa were significantly increased in KOA and significantly decreased by BZD. ELISA and Western blot analysis showed increased expression of subchondral bone pain-related neuropeptides SP, CGRP, TH, NPY, VEGFA, 5-HT3 in KOA, which were decreased in BZD. Functional magnetic resonance imaging demonstrated that BZD exerts its therapeutic effect on KOA by modulating the activity and functional connections of the cortex, hypothalamus, and hippocampus.

BackgroundBreast cancer (BC) is the most common cancer in women and is highly heterogeneous. BC can be classified into four molecular subtypes based on the status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker protein Ki-67. However, they can only be obtained by biopsy or surgery, which is invasive. Radiomics can noninvasively predict molecular expression via extracting the image features. Nevertheless, there is a scarcity of data available regarding the prediction of molecular biomarker expression using ultrasound (US) images in BC.ObjectivesTo investigate the prediction performance of US radiomics for the assessment of molecular profiling in BC.MethodsA total of 342 patients with BC who underwent preoperative US examination between January 2013 and December 2021 were retrospectively included. They were confirmed by pathology and molecular subtype analysis of ER, PR, HER2 and Ki-67. The radiomics features were extracted and four molecular models were constructed through support vector machine (SVM). Pearson correlation coefficient heatmaps are employed to analyze the relationship between selected features and their predictive power on molecular expression. The receiver operating characteristic curve was used for the prediction performance of US radiomics in the assessment of molecular profiling.Results359 lesions with 129 ER- and 230 ER+, 163 PR- and 196 PR+, 265 HER2- and 94 HER2+, 114 Ki-67- and 245 Ki-67+ expression were included. 1314 features were extracted from each ultrasound image. And there was a significant difference of some specific radiomics features between the molecule positive and negative groups. Multiple features demonstrated significant association with molecular biomarkers. The area under curves (AUCs) were 0.917, 0.835, 0.771, and 0.896 in the training set, while 0.868, 0.811, 0.722, and 0.706 in the validation set to predict ER, PR, HER2, and Ki-67 expression respectively.ConclusionUltrasound-based radiomics provides a promising method for predicting molecular biomarker expression of ER, PR, HER2, and Ki-67 in BC.

Abstract Chronic pain is the principal clinical manifestation of knee osteoarthritis (KOA) and an essential indicator of the diagnosis and treatment effect. Changes in brain functional activity are related with chronic pain in KOA. Bushen Zhuangjin Decoction (BZD) has been proved to reduce inflammation of arthritis, improve cartilage degeneration and analgesia, but whether it plays a role through the change of brain function activity is not clear. Here, three experiments were performed: (1) network pharmacology evaluation to discover the potential targets of BZD to relieve pain in KOA; (2) verification of the therapeutic effects of BZD treatment on KOA pain with histomorphology, behavioral assessments, suspension chip analysis, and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) assays; and (3) functional magnetic resonance imaging to explore the effects of BZD treatment on brain function associated to KOA. The analgesic effect of BZD on KOA was found to be related to the neurotransmitters of pain signals through network pharmacology and the therapeutic effect of BZD on KOA pain was verified in vivo, and related to neuropeptides and neurotransmitters. Functional magnetic resonance imaging showed that BZD treatment could reverse the regional homogeneity/amplitude of low-frequency fluctuation analysis in pain-related brain regions of KOA, suggesting that the analgesic mechanism of BZD is related to neural regulation. This study confirmed the key position of pain-related neuromodulation mechanisms in the analgesic therapy of BZD and provide a theoretical basis for the treatment of KOA pain with BZD as a traditional Chinese medical.

Osteoarthritis (OA) is a common joint disease characterized by chronic pain, and the perception of pain is closely associated with brain function and neuropeptide regulation. Rehmannia is common plant herb with anti-inflammatory and analgesic properties that is used to treat OA. However, it is unclear whether Rehmannia alleviates OA-related pain via regulation of neuropeptides and brain function. We examined the pain relief regulatory pathway in OA after treatment with Rehmannia by verifying the therapeutic effect of Rehmannia alcohol extract in vivo and vitro and exploring of the potential mechanism underlying the analgesic effect of Rahmanian using functional magnetic resonance imaging and measuring neuropeptide secretion. Our results showed that Rehmannia alcohol extract and the related active ingredient, Rehmannioside D, can delay cartilage degradation and alleviate inflammation in OA rats. The Rehmannia alcohol extract can also relieve OA pain, reduce the secretion of calcitonin gene-related peptide (CGRP) and substance P (SP), and reverse the pathological changes in the cerebral cortex and hippocampus. Our research results demonstrate that Rehmannia alleviates OA pain by protecting cartilage, preventing the stimulation of inflammatory factors on neuropeptide secretion, and influencing the relevant functional areas of the brain.

Endoplasmic reticulum stress (ERS) has been identified to be an important factor leading to chondrocyte apoptosis in osteoarthritis (OA). Previous studies have confirmed that Achyranthes bidentata polysaccharides (ABPS) can inhibit chondrocyte apoptosis; however, the mechanism of action of ABPS on chondrocyte ERS remains unclear. Thus in this study, we aim to investigate whether ABPS could inhibit OA-associated chondrocyte apoptosis by regulating ERS, especially by observing the relationship between the lncRNA NEAT1 and miR-377-3p, to explore further the protective mechanism of ABPS in OA. In vitro and in vivo experiments showed that ABPS inhibited chondrocyte ERS by regulating the expression of lncRNA NEAT1 and miR-377-3p. Moreover, both lncRNA NEAT1 silencing and miR-377-3p inhibition could attenuate the therapeutic effect of ABPS on ERS. Dual-luciferase results indicated that miR-377-3p targets the lncRNA NEAT1 gene in mouse chondrocytes. Therefore, we concluded that ABPS could inhibit thapsigargin (TG)-induced chondrocyte ERS through the lncRNA NEAT1/miR-377-3p axis.

Achyranthes bidentata polysaccharides (ABPS) is an active ingredient of the flowering plant Achyranthes bidentata that has been previously reported to be effective for the treatment of osteoarthritis (OA). However, the underlying molecular mechanism remain to be fully clarified. Emerging studies have shown that the long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) is involved in the pathogenesis of OA. Therefore, the present study aimed to investigate the potential mechanism of ABPS by focusing on its effects on the regulation of chondrocyte extracellular matrix (ECM) homeostasis, with particular emphasis on lncRNA GAS5. In the present study, the modified Hulth method was used to construct OA rats, which were gavaged with 400 mg/kg ABPS for 8 weeks. Histopathological changes in cartilage and subchondral bone were evaluated by hematoxylin-eosin staining and Safranin O-fast green staining. In in vitro experiments, IL-1β-treated chondrocytes were infected with Lenti-lncRNA GAS5. Fluorescence in situ hybridization assay was performed to measure the expression of the lncRNA GAS5 in chondrocytes. Moreover, the relative expression level of lncRNA GAS5 in cartilage tissue and chondrocytes was detected using reverse transcription-quantitative PCR. Western blot analysis was used to detect protein expression levels of MMP-9, MMP-13, TIMP-1, TIMP-3 and type II collagen in cartilage tissue and chondrocytes. The results indicated that ABPS delayed the degradation of the ECM by chondrocytes in addition to reducing lncRNA GAS5 expression both in vivo and in vitro. Furthermore, silencing of lncRNA GAS5 expression in IL-1β-treated chondrocytes downregulated the protein expression of MMP-9 and MMP-13 whilst upregulating the expression of tissue inhibitor matrix metalloproteinase (TIMP)-1, TIMP-3 and type II collagen. To conclude, the present study provides evidence that ABPS can inhibit the expression of lncRNA GAS5 in chondrocytes to regulate the homeostasis of ECM, which in turn may delay the occurrence of cartilage degeneration during OA.

Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) is the most common joint disease. The aim of my current academic work is to identify important genes associated with OA and RA, clarify their underlying mechanisms, and define differences between OA and RA.Methods: Gene expression profiles of GSE55235 were available from Gene Expression Omnibus database. Differentially expressed genes between 1) OA tissues and normal tissues, 2) RA tissues and normal tissues, were picked out by GEO2R tool, Venn diagram software, and Volcanic map. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery to analyze Kyoto Encyclopedia of Gene and Genome pathway and gene ontology. The protein-protein interaction of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes. Of entire PPI network analyzed by Molecular Complex Detection plug-in and obtain central nodes. Then the central nodes were re-analysis via DAVID. We next obtained the intersection of the analysis results of GSE55457 and GSE55235 to verify the results. Finally, potential biomarkers were evaluated by receiver operating characteristic.Results: Twelve genes were found to be significantly enriched in the TNF signaling pathway in OA, and eleven genes were found to be significantly enriched in the Chemokine signaling pathway in RA. Receiver operating characteristic curve suggested that the detection of JUN in OA and CCL5, CXCL9, CXCL10, CXCL11, CXCL13 in RA exhibited a high diagnostic performance.Conclusions: We have identified six significantly DEGs on the basis of integrated bioinformatical methods, which could be potential targets for differential diagnosis for OA and RA.

Although the targeted tyrosine kinase inhibitor imatinib mesylate (IM) has achieved significant responses against CML in the clinical setting, a small proportion of patients fail to respond to IM treatment and their disease continues to progress, indicating resistance to IM therapy. As a secreted extracellular matrix protein, cysteine-rich protein 61 (Cyr61) plays an important role in the resistance of solid tumors to chemotherapy, but its role in CML is unclear. In the present study, we observed that Cyr61 levels were upregulated in the plasma and bone marrow (BM) of patients with CML as well as in K562 cells. This upregulation of Cyr61 significantly decreased IM-induced cellular apoptosis of K562 cells through nuclear factor kappa B/B-cell lymphoma 2 pathways. Inhibition of Cyr61 restored the chemosensitivity of K562 cells to IM both in vitro and in vivo. Thus, our results showed for the first time that Cyr61 plays an important role in regulating the chemosensitivity of CML cells to IM, suggesting that selectively targeting Cyr61 directly or its relevant effector pathways may provide potential value in improving the clinical response of patients with CML to IM treatment.

Red blood cell distribution width (RDW) indicates the heterogeneity in the size of circulating red blood cells. Increasing studies showed that RDW may be a diagnostic and prognostic marker in various tumors. To investigate the value of RDW as a biomarker in the diagnosis and prognosis of colorectal cancer (CRC), we evaluated 783 newly diagnosed CRC patients, 463 colorectal adenomas (CA) patients, and 331 healthy controls from June 2015 to October 2017 at Fujian Medical University Union Hospital. We found that RDW levels were significantly higher in CRC groups compared with both the CA and healthy control groups (P<0.001). Receiver-operating characteristic (ROC) analysis showed that the area under the ROC curve (AUC) for RDW, CEA, and CA19-9 was 0.643, 0.742, and 0.629 in discriminating CRC patients from healthy controls, respectively. When RDW cut-off value of 13.95 was applied, we distinguished CRC patients from healthy controls with a sensitivity of 41% and a specificity of 94%. Moreover, combined detection of RDW, CEA, and CA19-9 appeared to be a better diagnostic performance with a sensitivity of 56% and a specificity of 99%. However, RDW had little diagnostic value in the differential diagnosis between CRC patients and CA patients. More importantly, RDW levels were significantly associated with TNM stage, pT stage, pM stage, and tumor size among CRC patients. Overall, our study suggested that RDW might be an auxiliary biomarker for diagnosis and prognosis of CRC.

To investigate the effect of Dan-gua Fang (a(1)c"eae-(1)) on adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) alpha expression in liver and subsequent improvement of glucose and lipid metabolism.Forty 13-week-old diabetic Goto-Kakizaki (GK) rats were randomly divided into model, Dan-gua Fang, metformin and simvastatin groups (n=10 for each), and fed high-fat diet ad libitum. Ten Wistar rats were used as normal group and fed normal diet. After 24 weeks, liver expression of AMPK alpha mRNA was assessed by real-time PCR. AMPK alpha and phospho-AMPK alpha protein expression in liver was evaluated by Western blot. Liver histomorphology was carried out after hematoxylin-eosin staining, and blood glucose (BG), glycosylated hemoglobin A1c (HbA1c), food intake and body weight recorded.Similar AMPK alpha mRNA levels were found in the Dan-gua Fang group and normal group, slightly higher than the values obtained for the remaining groups (P < 0.05). AMPK alpha protein expression in the Dan-gua Fang group animals was similar to other diabetic rats, whereas phospho-AMPK alpha (Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group (P < 0.05), respectively. However, phosphor-AMPK alpha/AMPK alpha ratios were similar in all groups. Dan-gua Fang reduced fasting blood glucose with similar strength to metformin, and was superior in reducing cholesterol, triglycerides, high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin. Dan-gua Fang decreases plasma alanine aminotransferase (ALT) significantly.Dan-gua Fang, while treating phlegm-stasis, could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet, and effectively protect liver histomorphology and function. This may be partly explained by increased AMPK expression in liver. Therefore, Dan-gua Fang might be an ideal drug for comprehensive intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.