Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer

BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.

Inhibition of M2 tumor-associated macrophages polarization by modulating the Wnt/β-catenin pathway as a possible liver cancer therapy method

The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol consumption.This deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver cancer.Huang et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin pathway.The interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular docking.It is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of neoplasms.It is assumed that M2 TAM promote proliferation and migration of tumor cells.Attempts to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological diseases.Undoubtedly,the work of the Chinese authors deserves attention and further development.

Exploration of the molecular mechanism of Qishen decoction in regulating miR-495/FTO pathway mediated macrophage polarization to improve insulin resistance therapy of type 2 diabetes

Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in the treatment of type 2 diabetes.Methods:THP-1 was induced to differentiate macrophages with phorbol ester.It was divided into the control group,the model group,the Qishen decoction group,the miR-495 inhibitor group,and the Qishen decoction+miR-495 inhibitor group.Except for the control group,the remaining groups were stimulated with 30 mmol/L glucose to construct a macrophage polarization model,and corresponding drugs were given for intervention.Cells were collected from each group for 24 hours and the content of inflammatory factors(IL-6,IL-1β,IL-4,and IL-10)were detected using enzyme-linked immunosorbent assay.The expression of macrophage polarization marker molecules,miR-495,and FTO were detected by flow cytometry,qPCR,and Western blot to detect.Results:Compared with the control group,there was no significant change in the activity of macrophages in the control serum,Qishen decoction containing serum,and miR-495 inhibitor transfected serum,and the difference was not statistically significant(P>0.05).In addition,compared to the control group,the content of IL-6 and IL-1β,the expression levels of CD68,iNOS,COX-2,miR-495,and the ratio of CD68/CD206,were significantly increased(P<0.01).While the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly reduced(P<0.01).Compared with the model group,the QiShen decoction significantly reduced the contents of IL-6 and IL-1β,and the expression levels of CD68,iNOS,COX-2,and miR-495,as well as the ratio of CD68/CD206,while the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly increased(P<0.01).Conclusion:Qishen decoction upregulate the expression of FTO to promote M2 type polarization of macrophages,thereby inhibiting inflammation and improving insulin resistance by inhibiting the expression of miR-495.

Poly(ADP-ribose)polymerase family member 14 promotes functional recovery after spinal cord injury through regulating microglia M1/M2 polarization via STAT1/6 pathway

Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains unclear.To investigate this,a T10 spinal cord contusion model was established in C57BL/6 mice,and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression.We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury,accompanied by obvious neuronal apoptosis,severe neuroinflammation,and slight bone loss.Furthermore,PARP14 levels were elevated in microglia after SCI,PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia(anti-inflammatory phenotype)to M1-polarized microglia(pro-inflammatory phenotype)that may have been mediated by the signal transducers and activators of transcription(STAT)1/6 pathway.Next,microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γand interleukin-4,respectively.The results showed that PARP14 knockdown promoted microglia M1 polarization,accompanied by activation of the STAT1 pathway.In addition,PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway.In conclusion,these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.

Rutin pretreatment promotes microglial M1 to M2 phenotype polarization

Microglial cells are important resident innate immune components in the central nervous system that are often activated during neuroinflammation.Activated microglia can display one of two phenotypes,M1 or M2,which each play distinct roles in neuroinflammation.Rutin,a dietary flavonoid,exhibits protective effects against neuroinflammation.However,whether rutin is able to influence the M1/M2 polarization of microglia remains unclear.In this study,in vitro BV-2 cell models of neuroinflammation were established using 100 ng/mL lipopolysaccharide to investigate the effects of 1-hour rutin pretreatment on microglial polarization.The results revealed that rutin pretreatment reduced the expression of the proinflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6 and increased the secretion of interleukin-10.Rutin pretreatment also downregulated the expression of the M1 microglial markers CD86 and inducible nitric oxide synthase and upregulated the expression of the M2 microglial markers arginase 1 and CD206.Rutin pretreatment inhibited the expression of Toll-like receptor 4 and myeloid differentiation factor 88 and blocked the phosphorylation of I kappa B kinase and nuclear factor-kappa B.These results showed that rutin pretreatment may promote the phenotypic switch of microglia M1 to M2 by inhibiting the Toll-like receptor 4/nuclear factor-kappa B signaling pathway to alleviate lipopolysaccharide-induced neuroinflammation.

C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental post-stroke cognitive impairment by enhancing microglia/macrophage M2 polarization

BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells.However,the effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUC-MSCs)(ExoCtrl)on post-stroke cognitive impairment(PSCI)have rarely been reported.Moreover,whether exosomes derived from C-C chemokine receptor type 2(CCR2)-overexpressing HUC-MSCs(ExoCCR2)can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied.AIM To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI.METHODS Transmission electron microscopy,qNano®particles analyzer,and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2.ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2(CCL2)in vivo.After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats,the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze.Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy.QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization.The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis.RESULTS CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes.The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference.ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding.Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI,oligodendrogenesis,remyelination,and microglia/macrophage polarization,ExoCCR2 exhibited a significantly superior beneficial effect.We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activation in vivo and in vitro,compared with ExoCtrl treated group.CONCLUSION CCR2 over-expression enhanced the therapeutic effects of exosomes on the experimental PSCI by promoting M2 microglia/macrophage polarization,enhancing oligodendrogenesis and remyelination.These therapeutic effects are likely through suppressing the CCL2-induced hematogenous macrophage migration and activation.Key words:Cognitive impairment;Stroke;Exosomes;C-C chemokine receptor type 2;Microglia/macrophage polarization;Remyelination.

Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

Effect of Pingchuan granule on typeⅡinnate lymphocytes and M2 polarization of macrophages in asthmatic mice

Objective:To observe the effect of Pingchuan granule on the number of typeⅡinnate lymphocytes(ILC2)and M2 polarization of macrophages in the lung tissue of asthmatic mice;Methods:Ovalbumin sensitized and challenged asthmatic mouse models were established,and then Pingchuan granules or IL-33 neutralizing antibody were given to intervene.The pathological morphology of lung tissue was observed by HE,PAS and Masson staining,and the expressions of IL-4,IL-5,IL-13 and IL-33 in BALF and lung tissue were detected by ELISA and qRT-PCR,Flow cytometry was used to detect the number of type II innate lymphocytes and type M2 macrophages in lung tissue.Western blot was used to detect the protein expression levels of ST-2,FIZZ1 and Arg-1 in lung tissue;Results:Compared with the control group,the inflammation score,PAS score and collagen staining area of the model group were significantly increased,the expressions of IL-4,IL-5,IL-13 and IL-33 in BALF and lung tissue were significantly increased,the number of ILC2 and M2 macrophages,the expression of ST-2,FIZZ1 and Arg-1 protein in lung tissue were significantly increased,and the differences were statistically significant(P<0.05);Compared with the model group,Pingchuan granule could significantly reduce the inflammation score,PAS score and collagen staining area of asthmatic mice,down-regulate the expression of IL-4,IL-5,IL-13 and IL-33 in BALF and lung tissue,reduce the number of ILC2 and M2 macrophages,and the expression of ST-2,FIZZ1 and Arg-1 protein in lung tissue(P<0.05);Conclusion:Pingchuan granule improve the airway remodeling of asthma by inhibiting the polarization of M2 macrophages mediated by ILC2.

Th1/Th2、M1-M2与2型糖尿病慢性牙周炎病变程度及预后的关系

目的探讨2型糖尿病(T2DM)合并慢性牙周炎(CP)患者辅助性T细胞1型/辅助性T细胞2型(Th1/Th2)失衡及巨噬细胞M1-M2极化,以及其与牙周炎病变程度和治疗预后的关系。方法采用前瞻性研究方法,纳入2022年1月至2023年6月在宝鸡市人民医院口腔科治疗的80例T2DM合并CP患者作为研究对象,根据CP严重程度分为轻度组(57例)和中重度组(23例),治疗后根据预后分为预后良好组(33例)和预后差组(47例)。轻度组男28例、女29例,年龄(48.00±6.03)岁,T2DM病程(3.54±1.15)年,CP病程(12.54±4.65)个月;中重度组男11例、女12例,年龄(50.48±6.65)岁,T2DM病程(3.79±1.55)年,CP病程(12.71±4.76)个月。采用流式细胞术评估Th1/Th2细胞比例,通过实时定量PCR分析牙周组织中M1型与M2型巨噬细胞标志物的表达。采用Pearson相关性分析Th1/Th2细胞比例、M1/M2极化状态与牙周炎临床参数及预后之间的相关性。统计学方法采用t检验、χ^(2)检验。结果中重度组Th1、Th1/Th2细胞比例及肿瘤坏死因子(TNF)-α、白细胞介素(IL)-2、IL-4、IL-6、IL-10、IL-1β、IL-12、IL-17、TNF-β、信号转导和转录激活因子1(STAT1)、诱导型一氧化氮合酶(iNOS)、信号转导和转录激活因子6(STAT6)mRNA、精氨酸酶1(Arg1)mRNA指标均高于轻度组[(2.62±0.53)%比(1.62±0.41)%、(2.47±0.53)比(1.21±0.27)、(51.83±6.25)ng/L比(36.74±5.47)ng/L、(27.54±50.00)μg/L比(14.58±4.65)μg/L、(72.63±8.95)ng/L比(46.68±6.57)ng/L、(41.85±2.61)ng/L比(37.08±3.54)ng/L、(4.76±1.13)ng/L比(3.87±1.16)ng/L、(23.10±5.86)μg/L比(16.78±2.54)μg/L、(11.76±5.37)ng/L比(9.16±2.16)ng/L、(12.78±2.14)μg/L比(10.54±1.63)μg/L、(1370.0±160.0)μg/L比(910.0±140.0)μg/L、(800.0±180.0)μg/L比(260.0±110.0)μg/L、(930.0±190.0)μg/L比(430.0±110.0)μg/L、(760.0±130.0)μg/L比(560.0±90.0)μg/L、(710.0±120.0)μg/L比(490.0±80.0)μg/L],Th2细胞比例及干扰素-γ(IFN-γ)、IL-23水平均低于轻度组[(1.06±0.37)%比(1.34±0.41)%、(4.21±0.65)ng/L比(4.85±0.67)ng/L、(6.84±0.83)ng/L比(14.65±1.81)ng/L],差异均有统计学意义(t=9.05、14.06、10.71、10.69、14.35、5.84、3.12、6.76、3.10、5.07、12.76、16.37、14.73、7.87、9.57、2.84、3.95、19.81,均P<0.05)。患者牙周炎病变程度与Th1、Th1/Th2、TNF-α、IL-2、IL-4、IL-6、IL-10、IL-1β、IL-12、IL-17、TNF-β、STAT1、iNOS、STAT6 mRNA、Arg1 mRNA均呈正相关(均P<0.01);与Th2、INF-γ、IL-23均呈负相关(均P<0.01)。预后良好组Th1、Th1/Th2细胞比例及TNF-α、IL-1β水平均低于预后差组[(1.31±0.21)%比(2.62±0.75)%、(0.94±0.21)比(2.70±0.48)、(34.81±4.51)ng/L比(55.23±7.31)ng/L、(15.84±2.89)μg/L比(24.56±4.74)μg/L],Th2细胞比例高于预后差组[(1.39±0.24)%比(0.97±0.37)%],差异均有统计学意义(t=9.75、19.74、14.24、9.40、5.72,均P<0.05)。结论T2DM合并CP患者Th1/Th2失衡及M1-M2极化状态变化与牙周病变程度和治疗预后密切相关,调节免疫反应对改善T2DM患者牙周病变和预后具有潜在的临床意义。

Type 2 Diabetes—Hard to Select a Healthy Choice

Introduction: The use of foods containing high levels of sugar is increasing all the time. This is a risk factor for increased incidence of type 2 diabetes. There are few studies that have investigated the availability of low-sugar müsli products in grocery stores. Purpose: The study aims to identify which types of müsli contain high respectively low levels of sugar, and which brands are involved. Methods: The material consists of both qualitative interviews and observations from five grocery stores: City Gross, Hemköp, Ica Maxi, Stora Coop and Willy’s in Helsingborg, Sweden. The qualitative interviews had a semi-structured character and were recorded. The interviews took approx. 20 minutes and a textual analysis was conducted of the results. Data from observation was analyzed based on brand, nutritional composition and flavors, and also, where low sugar products were placed on store shelves. Results: The grocery stores provided together brands from AXA, Coop, Finax, Frebaco, Garant, ICA, Risenta, Saltå Kvarn och Urtekram, in total 24 müsli products. Of these products, 19 were high in sugar. The observation reveals that müsli products with high sugar content (17 - 29 g per 100 g müsli) are more prominently displayed than those with low sugar content. From the interviews with the store managers, it became clear that it would be valuable to highlight healthy müsli products on the shelves. However, central bureaucracy puts obstacles to such measures. Discussion: The study emphasizes the need for increased visibility of low-sugar products and proposes solutions such as negotiating with responsible person at the head office in Stockholm. Several reviews have shown that if the grocery store raises the prices of unhealthy food, the consumer is willing to purchase healthier müsli and other products. Conclusion: This study shows the need for grocery stores to upgrade healthy müsli products along with advertising to be able to influence customer’s shopping habits. Also, further research is needed how type 2 diabetes is affected by high intakes of food products with high sugar content.

极区电离层N_(m)F_(2)观测与国际参考电离层对比研究

利用南北极极隙区与极光带纬度3个台站对电离层F2层峰值电子密度(N_(m)F_(2))长达1个太阳活动周的观测数据,对国际参考电离层IRI-2016模型在极区的适用性进行系统的定量研究。结果表明,在极光带纬度的北极Tromsø站,IRI预测与观测符合最好,大部分季节相对误差在40%以内,在太阳活动高年略好于太阳活动低年。在极隙区纬度的南极中山站和Longyearbyen站,IRI预测精度在太阳活动低年高于太阳活动高年。在中山站和北极Longyearbyen站仅个别月份相对误差在20%以内,大部分月份相对误差超过40%,冬季相对误差接近100%,特别是Longyearbyen站,在太阳活动高年冬季相对误差超过100%。从季节上看,3个台站都是冬季符合最差,夏季符合最好。IRI-2016模型对极区电离层进行预测时,难以如实反映极区等离子体对流和能量粒子沉降等极区特有的物理过程对极区电离层N_(m)F_(2)的影响。

Rapid detection of PPARy gene Prol2Ala polymorphism with fluorescence polarization in Chinese population

Objective: Peroxisome proliferator-activated receptor -γ(PPAR-γ) plays a critical role in adipocyte differentiation and the development of type 2 diabetes mellitus (T2DM). Numerous studies across several populations have indicated that Pro12Ala polymorphism of PPAR-γ is associated with decreased insulin resistance and decreased risk of T2DM. The aims of this study are to develop a simple and sensitive detection of Pro12Ala polymorphism and examined the distribution of this polymorphism in Chinese population. Methods: The PPAR-γ gene fragment containing Pro12Ala variant of 101 T2DM patients and 104 controls were amplified by PCR amplification and the extension reaction was performed using primer that adjacent to the single nucleotide polymorphic site in presence of two different dye-labeled terminators. The primer's specially extending reactions make the increase of their fluorescence polarization (FP) that mean special genotype. The variant frequencies of the two groups were compared. Results: We detected the Pro12Ala variant successfully by TDI-FP method and we found no significant association between this polymorphism and T2DM in case-control study. Conclusion: The TDI-FP technology is a new specific and sensitive method that is suitable for automatic detection of large number of clinical samples. Prol2Ala mutation in PPAR--@2 gene does not play a significant role in T2DM risk in Chinese population.

血清PCSK9、vWF和apoM水平在2型糖尿病并发大血管病变中的诊断价值

目的观察血清转化酶枯草溶菌素9(PCSK9)、血管性假血友病因子(vWF)和载脂蛋白M(apoM)水平在2型糖尿病并发大血管病变中的诊断价值。方法选择2018年1月至2021年6月在该院就诊的210例2型糖尿病患者纳入2型糖尿病组。选择同期在该院行健康体检的75例健康者纳入健康对照组。根据大血管病变的诊断标准将2型糖尿病患者分为单纯糖尿病组(118例)和大血管病变组(92例)。观察各组血清PCSK9、vWF和apoM水平变化,对2型糖尿病并发大血管病变进行单因素和多因素分析,比较2型糖尿病患者治疗前后血清PCSK9、vWF和apoM水平变化,并分析3项指标在2型糖尿病并发大血管病变中的诊断效能。结果2型糖尿病组血清PCSK9和vWF水平明显高于健康对照组,而血清apoM水平明显低于健康对照组,差异有统计学意义(P<0.05)。治疗前大血管病变组血清PCSK9和vWF水平明显高于单纯糖尿病组,差异有统计学意义(P<0.05);治疗后两组血清PCSK9和vWF水平均较治疗前明显降低,但大血管病变组仍高于单纯糖尿病组,差异有统计学意义(P<0.05)。治疗前大血管病变组血清apoM水平明显低于单纯糖尿病组,差异有统计学意义(P<0.05);治疗后两组血清apoM水平均较治疗前明显升高,但大血管病变组仍低于单纯糖尿病组,差异有统计学意义(P<0.05)。单因素分析显示,大血管病变组年龄≥60岁及糖尿病病程≥10年比例、甘油三酯和低密度脂蛋白胆固醇水平明显高于单纯糖尿病组,差异有统计学意义(P<0.05)。多因素分析显示PCSK9、vWF水平升高是2型糖尿病并发大血管病变的独立危险因素(P<0.05),血清apoM水平升高是2型糖尿病并发大血管病变的保护因素(P<0.05)。血清PCSK9、vWF和apoM联合检测诊断2型糖尿病并发大血管病变的灵敏度为89.1%,特异度为90.7%,曲线下面积(AUC)为0.956,AUC明显高于PCSK9(Z=4.167,P<0.01)、vWF(Z=4.056,P<0.01)和apoM(Z=5.183,P<0.01)单项指标检测,而3项指标之间的AUC差异无统计学意义(P>0.05)。结论PCSK9、vWF和apoM参与了2型糖尿病并发大血管病变的过程,3项指标联合检测对诊断2型糖尿病并发大血管病变具有较高的效能。

基于miR-495/FTO通路介导的巨噬细胞极化探讨芪参汤改善胰岛素抵抗治疗2型糖尿病的分子机制

目的:观察芪参汤对miR‐495/FTO信号通路介导的巨噬细胞极化的影响,从而阐明芪参汤改善胰岛素抵抗治疗2型糖尿病的分子机制。方法:以佛波酯诱导THP‐1人单核细胞株分化巨噬细胞,并分为空白组、模型组、芪参汤组、miR‐495 inhibitor组和芪参汤+miR‐495 inhibitor组。除空白组外,余下各组采用30 mmol/L葡萄糖刺激构建巨噬细胞极化模型,并给与相应的药物进行干预。24 h收集各组细胞,采用酶联免疫吸附法检测炎症因子(IL‐6、IL‐1β、IL‐4和IL‐10)的含量,采用流式细胞术、qPCR和Western blot检测巨噬细胞极化标记分子、MiR‐495和FTO的表达。结果:与空白组相比,空白血清、芪参汤含药血清和转染miR‐495抑制物的巨噬细胞活性均无明显变化,差异均无统计学意义(P>0.05)。此外,与空白组相比,模型组IL‐6和IL‐1β的含量、CD68、iNOS、COX‐2和miR‐495的表达和CD68/CD206的比值均显著增加,IL‐4和IL‐10的含量、CD206、Arg‐1、YM‐1和FTO的表达均显著降低,差异均具有统计学意义(P<0.01)。与模型组相比,芪参汤组IL‐6和IL‐1β的含量、CD68、iNOS、COX‐2和miR‐495的表达和CD68/CD206的比值均显著降低,IL‐4和IL‐10的含量、CD206、Arg‐1、YM‐1和FTO的表达均显著增加,差异均具有统计学意义(P<0.01)。结论:芪参汤靶向miR‐495上调/FTO的表达促进巨噬细胞的M2型极化,从而抑制炎症达到改善胰岛素抵抗的作用。

Exosomal microRNA-588 from M2 polarized macrophages contributes to cisplatin resistance of gastric cancer cells

BACKGROUND Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally.Cisplatin(DDP)is one of the most common and effective chemotherapies for patients with gastric cancer,but DDP resistance remains a severe clinical challenge.AIM To explore the function of M2 polarized macrophages-derived exosomal microRNA(miR)-588 in the modulation of DDP resistance of gastric cancer cells.METHODS M2 polarized macrophages were isolated and identified by specific markers using flow cytometry analysis.The exosomes from M2 macrophages were identified by transmission electron microscopy and related markers.The uptake of the PKH67-labelled M2 macrophages-derived exosomes was detected in SGC7901 cells.The function and mechanism of exosomal miR-588 from M2 macrophages in the modulation of DDP resistance of gastric cancer cells was analyzed by CCK-8 assay,apoptosis analysis,colony formation assay,Western blot analysis,qPCR analysis,and luciferase reporter assay in SGC7901 and SGC7901/DDP cells,and by tumorigenicity analysis in nude mice.RESULTS M2 polarized macrophages were isolated from mouse bone marrow stimulated with interleukin(IL)-13 and IL-4.Co-cultivation of gastric cancer cells with M2 polarized macrophages promoted DDP resistance.M2 polarized macrophagesderived exosomes could transfer in gastric cancer cells to enhance DDP resistance.Exosomal miR-588 from M2 macrophages contributed to DDP resistance of gastric cancer cells.miR-588 promoted DDP-resistant gastric cancer cell growth in vivo.miR-588 was able to target cylindromatosis(CYLD)in gastric cancer cells.The depletion of CYLD reversed miR-588 inhibition-regulated cell proliferation and apoptosis of gastric cancer cells exposed to DDP.CONCLUSION In conclusion,we uncovered that exosomal miR-588 from M2 macrophages contributes to DDP resistance of gastric cancer cells by partly targeting CYLD.miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.

Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening:A meta-analysis

AIM:To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2(faecal M2-PK) test for colorectal cancer(CRC) screening based on the currently available studies.METHODS:A literature search in PubMed and Embase was conducted using the following search terms:fecal Tumor M2-PK,faecal Tumour M2-PK,fecal M2-PK,faecal M2-PK,fecal pyruvate kinase,faecal pyruvate kinase,pyruvate kinase stool and M2-PK stool.RESULTS:Stool samples from 704 patients with CRC and from 11 412 healthy subjects have been investigated for faecal M2-PK concentrations in seventeen independent studies.The mean faecal M2-PK sensitivity was 80.3%;the specificity was 95.2%.Four studies compared faecal M2-PK head-to-head with guaiacbased faecal occult blood test(gFOBT).Faecal M2PK demonstrated a sensitivity of 81.1%,whereas the gFOBT detected only 36.9% of the CRCs.Eight independent studies investigated the sensitivity of faecal M2-PK for adenoma(n = 554),with the following sensitivities:adenoma < 1 cm in diameter:25%;adenoma > 1 cm:44%;adenoma of unspecified diameter:51%.In a direct comparison with gFOBT of adenoma > 1 cm in diameter,47% tested positive with the faecal M2-PK test,whereas the gFOBT detected only 27%.CONCLUSION:We recommend faecal M2-PK as a routine test for CRC screening.Faecal M2-PK closes a gap in clinical practice because it detects bleeding and nonbleeding tumors and adenoma with high sensitivity and specificity.

Nonsingularity on Level-2(r_1, r_2)-circulant Matrices of Type (m,n)

In this pape,we give four methods of discriminations its nonsingularity by utilizing only parametr r1,r2 and elements of the first row of level-2 (r1, r2)-circulant matrices of type (m,n).

Unveiling the anticancer effect of traditional Chinese herbal medicine

In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver cancer.Although the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.

Deployment of Polar Codes for Mission-Critical Machine-Type Communication Over Wireless Networks

Mission critical Machine-type Communication(mcMTC),also referred to as Ultra-reliable Low Latency Communication(URLLC),has become a research hotspot.It is primarily characterized by communication that provides ultra-high reliability and very low latency to concurrently transmit short commands to a massive number of connected devices.While the reduction in physical(PHY)layer overhead and improvement in channel coding techniques are pivotal in reducing latency and improving reliability,the current wireless standards dedicated to support mcMTC rely heavily on adopting the bottom layers of general-purpose wireless standards and customizing only the upper layers.The mcMTC has a significant technical impact on the design of all layers of the communication protocol stack.In this paper,an innovative bottom-up approach has been proposed for mcMTC applications through PHY layer targeted at improving the transmission reliability by implementing ultra-reliable channel coding scheme in the PHY layer of IEEE 802.11a standard bearing in mind short packet transmission system.To achieve this aim,we analyzed and compared the channel coding performance of convolutional codes(CCs),low-density parity-check(LDPC)codes,and polar codes in wireless network on the condition of short data packet transmission.The Viterbi decoding algorithm(VA),logarithmic belief propagation(Log-BP)algorithm,and cyclic redundancy check(CRC)successive cancellation list(SCL)(CRC-SCL)decoding algorithm were adopted to CC,LDPC codes,and polar codes,respectively.Consequently,a new PHY layer for mcMTC has been proposed.The reliability of the proposed approach has been validated by simulation in terms of Bit error rate(BER)and packet error rate(PER)vs.signal-to-noise ratio(SNR).The simulation results demonstrate that the reliability of IEEE 802.11a standard has been significantly improved to be at PER=10−5 or even better with the implementation of polar codes.The results also show that the general-purpose wireless networks are prominent inproviding short packet mcMTC with the modification needed.

阶跃光纤低阶线偏振模的M^2因子分析

针对阶跃光纤输出低阶线偏振模(Linear Polarization,LP),利用二阶距定束宽,多点拟合法计算了几个低阶LPmn模相干和非相干叠加时的M2因子.结果表明,对同一LPmn模式,光纤的归一化频率参量V减小到截止频率时,M2因子出现峰值;当V远离截止频率时M2因子趋于一定值.低阶LPmn模非相干叠加时,叠加后的较高阶模成分越大,合成光束的光束质量越差,光束在一定的条件下可能比基模更接近于理想高斯光束;而相干叠加时,合成后的M2因子可以大于参与叠加的较高阶模的光束质量因子.