The Gut‒Breast Axis: Programming Health for Life

The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.     

Anticancer Mechanism of Curcumin on Human Glioblastoma

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.     

Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota

Foxtail millet (FM) is receiving ongoing increased attention due to its beneficial health effects, including the hypoglycemic effect. However, the underlying mechanisms of the hypoglycemic effect have been underexplored. In the present study, the hypoglycemic effect of FM supplementation was confirmed again in high-fat diet and streptozotocin-induced diabetic rats with significantly decreased fasting glucose (FG), glycated serum protein, and areas under the glucose tolerance test (p < 0.05). We employed 16S rRNA and liver RNA sequencing technologies to identify the target gut microbes and signaling pathways involved in the hypoglycemic effect of FM supplementation. The results showed that FM supplementation significantly increased the relative abundance of Lactobacillus and Ruminococcus_2, which were significantly negatively correlated with FG and 2-h glucose. FM supplementation significantly reversed the trends of gene expression in diabetic rats. Specifically, FM supplementation inhibited gluconeogenesis, stimulated glycolysis, and restored fatty acid synthesis through activation of the PI3K/AKT signaling pathway. FM also reduced inflammation through inhibition of the NF-κB signaling pathway. Spearman’s correlation analysis indicated a complicated set of interdependencies among the gut microbiota, signaling pathways, and metabolic parameters. Collectively, the above results suggest that the hypoglycemic effect of FM was at least partially mediated by the increased relative abundance of Lactobacillus, activation of the PI3K/AKT signaling pathway, and inhibition of the NF-κB signaling pathway.     

腹主动脉瘤腔内修复术后感染病原菌及Hippo信号通路基因改变

目的探讨腹主动脉瘤腔内修复术(EVAR)后医院感染病原特点及Hippo信号通路基因、白细胞介素-17(Interleukin-17,IL-17)、IL-23改变。方法选择天津医院血管外科2017年5月-2020年3月收治腹主动脉瘤EVAR术后医院感染患者49例作为感染组,选择同期医院进行EVAR术后未发生医院感染患者60例作为非感染组。采用实时荧光定量逆转录聚合酶链反应(RT-PCR)法检测Hippo通路基因yap、taz、mst1相对表达水平,采用酶联免疫吸附法检测其辅助型T细胞17(Th17)促炎细胞因子白细胞介素-17(IL-17)、IL-23水平。结果49例患者共发生肺部感染33例(67.35%),尿路感染10例(20.41%),手术切口感染4例(8.16%),移植物感染2例(4.08%);感染病原以革兰阳性菌为主,共25株,占51.02%,革兰阴性菌共22株,占44.90%,真菌2株,占4.08%;感染组yap、taz、mst1基因相对表达水平和IL-17、IL-23水平高于非感染组(P<0.05)。结论腹主动脉瘤EVAR术后医院感染以肺部感染、尿路感染为主,应及时予以针对性预防;Hippo通路参与了感染发生过程,通过Th17促炎途径诱导炎症反应,其机制仍有待研究。     

慢性乙型肝炎患者外周血SOCS3 mRNA的表达及其与Th17的关系

 目的 研究慢性乙型肝炎(CHB)患者外周血辅助性T细胞17(Th17)以及细胞因子信号转导抑制因子3(SOCS3) mRNA的表达状况,探索CHB患者SOCS3 mRNA表达与Th17的关系。方法 选取2021年2—8月于某院门诊就诊的30例CHB患者为研究对象,并选取同期正常体检者15例为对照组。采用流式细胞术(FCM)检测外周血Th17细胞频数,酶联免疫吸附试验(ELISA)检测血清细胞因子IL-17A和IL-23表达水平,实时荧光定量逆转录聚合酶链反应(qRT-PCR)法测定外周血SOCS3、维甲酸相关孤儿核受体γt (RORγt) mRNA表达水平,并比较两组患者的检测结果。结果 CHB患者外周血Th17细胞频数及其效应分子IL-17A、IL-23表达水平高于对照组(均P＜0.05),Th17细胞频数、IL-17A与HBV DNA水平之间存在正相关(r值分别为0.570、0.563,均P＜0.005)。CHB患者外周血SOCS3、RORγt mRNA表达水平高于对照组(均P＜0.05),两者与HBV DNA水平正相关(r值分别为0.662、0.561,均P＜0.05)。CHB患者SOCS3 mRNA与RORγt mRNA、Th17细胞频数、IL-17A之间存在正相关(r值分别为0.552、0.626、0.826,均P＜0.05)。结论 CHB患者外周血SOCS3 mRNA的异常高表达,可能通过调节RORγt mRNA的表达来影响Th17的分化及其效应分子的分泌。     

A novel adipokine WISP1 attenuates lipopolysaccharide-induced cell injury in 3T3-L1 adipocytes by regulating the PI3K/Akt pathway

BackgroundTo study the effect of WISP1 on lipopolysaccharide (LPS)-induced cell injury in 3T3-L1 adipocytes.MethodLentivirus was transiently transfected into log phase 3T3-L1 adipocytes, which were then treated with LPS at a concentration of 10 μg/mL for 24 h. The cells were divided into the following groups: group A (control, untreated cells); group B (LPS-treated cells); group C (GFP), cells transfected with lentivirus-containing GFP; group D (GFP+LPS), group C treated with LPS;group E (WISP1OE), cells transfected with lentivirus, group F (shNC+LPS), cells transfected with lentivirus-containing nshRNA treated with LPS; group G (shWISP1 +LPS), cells transfected with lentivirus-containing shRNA treated with LPS; group H (WISP1OE+LPS), group E treated with LPS; group I (WISP1OE+LPS+LY294002), group E treated with LPS followed by LY294002 for 24 h.ResultsWISP1 overexpression notably ameliorated cell apoptosis, accompanied with the increased expression of bcl-2, the decreased expressions of bax and cleaved-caspase-3, and promoted the release of inflammatory factors, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-treated 3T3-L1 adipocytes. WISP1 knockdown exhibited the opposite results. In addition, WISP1 stimulated Akt phosphorylation and reduced nuclear translocation of Fork head box protein O3 (FoxO3a) in 3T3-L1 adipocytes treated by LPS. The inhibition of the PI3K/Akt signaling pathway diminished the protective effect of WISP1.ConclusionWISP1 prevents 3T3-L1 adipocytes from being injured by LPS by regulating the PI3K/Akt pathway.     

丝裂素活化蛋白激酶介导~(60)Coγ射线抑制血管平滑肌细胞增生的机制

目的研究60 Coγ射线对平滑肌细胞增殖的影响及机制。方法采用同位素技术 ,测定3 H TdR掺入和丝裂素活化蛋白激酶 (MAPK)活性。结果 1 4、2 8Gy60 Coγ射线明显抑制平滑肌细胞增殖 ,同时MAPK活性明显下降。结论 60　Coγ射线抑制平滑肌细胞增殖可能是通过降低MAPK活性途径实现的。     

非靶向代谢组学揭示天葵不同部位差异代谢物及其主要代谢途径

目的:利用非靶向代谢组学挖掘天葵非药用部位潜在的药用价值。方法:以天葵茎、叶、花为材料,利用超高效液相色谱-质谱法对其进行非靶向代谢组学分析。结果:天葵茎、叶、花中共鉴定出16大类101个差异代谢物(DAMs),其中包含羧酸及其衍生物、有机含氧化合物、脂质、苯及其取代衍生物、生物碱、黄酮类、萜类、苯丙素类、酚酸类、核苷酸、有机盐、内酯、有机酸、内源性植物激素、氨基酸和13个其他物质。通过聚类和京都基因与基因组百科全书(KEGG)分析发现,天葵不同部位的DAMs代谢模式存在一定的差异;其主要代谢途径为苯丙氨酸代谢途径、ABC转运途径、氨酰-tRNA合成途径及苯丙氨酸、酪氨酸和色氨酸生物合成途径。结论:通过天葵不同部位间DAMs的鉴定及其生物合成途径的分析,确定天葵茎、叶、花富含多种具有药用功效的代谢活性物质,可为天葵茎、叶、花的资源开发利用提供参考。     

基于Raf-MEK-ERK信号通路探究梓醇对蛛网膜下腔出血大鼠脑组织损伤的影响

[目的] 通过考察梓醇对蛛网膜下腔出血（SAH）大鼠脑组织丝/苏氨酸蛋白激酶（Raf）-丝裂原活化蛋白激酶（MEK）-细胞外调节蛋白激酶（ERK）信号通路的影响,探讨其抗SAH脑损伤的作用机制。[方法] 将大鼠随机分为假手术组、SAH组、梓醇组、梓醇+U0126组（梓醇+Raf-MEK-ERK信号通路抑制剂U0126）。采用血管内穿孔法构建大鼠SAH模型,评估大鼠神经功能和SAH分级,伊文思蓝（EB）检测血脑屏障通透性,苏木素-伊红（HE）染色观察脑组织病理变化,免疫荧光染色检测神经元细胞凋亡及微管连接蛋白轻链3-Ⅱ（LC3-Ⅱ）、p-ERK阳性细胞表达,蛋白免疫印迹（Western blot）检测脑组织Raf、MEK、磷酸化（p）-MEK、ERK1/2、p-ERK1/2、B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、自噬基因Beclin-1、LC3-Ⅱ表达。[结果] 与假手术组相比,SAH组神经元细胞排列松散,数目减少,SAH分级、脑组织含水量、EB渗出量、原位末端标（TUNEL）阳性细胞数显著增加,凋亡率、LC3-Ⅱ、p-ERK阳性表达、Bax、Beclin-1、LC3-Ⅱ、Raf、p-MEK/MEK、p-ERK1/2/ERK1/2表达显著升高,神经功能评分减少,Bcl-2蛋白表达降低（P<0.05）;与SAH组相比,梓醇组神经元损伤明显减轻,细胞死亡较少,SAH分级、脑组织含水量、EB渗出量、TUNEL阳性细胞数显著减少,凋亡率、Bax显著降低,神经功能评分、Bcl-2表达升高,LC3-Ⅱ、p-ERK阳性表达及Beclin-1、LC3-Ⅱ、Raf、p-MEK/MEK、p-ERK1/2/ERK1/2表达进一步升高（P<0.05）;Raf-MEK-ERK通路抑制剂U0126可逆转梓醇对脑组织损伤的改善作用（P<0.05）。[结论] 梓醇可能通过激活Raf-MEK-ERK信号通路,促进神经细胞自噬,改善SAH大鼠脑损伤。