Molecular Mechanisms of Flavonoids against Tumor Gamma-Herpesviruses and Their Correlated Cancers—A Focus on EBV and KSHV Life Cycles and Carcinogenesis

Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to achieving effective therapies for viral infections and cancer. Thus, new medications with dual antiviral and anticancer actions are highly needed. Flavonoids are secondary metabolites biosynthesized by plants with diverse therapeutic effects on human health. In this review, we feature the potential role of flavonoids (flavones, protoflavones, isoflavones, flavanones, flavonols, dihydroflavonols, catechins, chalcones, anthocyanins, and other flavonoid-type compounds) in controlling gamma-herpesvirus-associated cancers by blocking EBV and KSHV infections and inhibiting the formation and growth of the correlated tumors, such as nasopharyngeal carcinoma, Burkitt’s lymphoma, gastric cancer, extranodal NK/T-cell lymphoma, squamous cell carcinoma, Kaposi sarcoma, and primary effusion lymphoma. The underlying mechanisms via targeting EBV and KSHV life cycles and carcinogenesis are highlighted. Moreover, the effective concentrations or doses are emphasized.     

Blocking Muscarinic Receptor 3 Attenuates Tumor Growth and Decreases Immunosuppressive and Cholinergic Markers in an Orthotopic Mouse Model of Colorectal Cancer

Tumor cells have evolved to express immunosuppressive molecules allowing their evasion from the host’s immune system. These molecules include programmed death ligands 1 and 2 (PD-L1 and PD-L2). Cancer cells can also produce acetylcholine (ACh), which plays a role in tumor development. Moreover, tumor innervation can stimulate vascularization leading to tumor growth and metastasis. The effects of atropine and muscarinic receptor 3 (M3R) blocker, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP), on cancer growth and spread were evaluated in vitro using murine colon cancer cell line, CT-26, and in vivo in an orthotopic mouse model of colorectal cancer. In the in vitro model, atropine and 4-DAMP significantly inhibited CT-26 cell proliferation in a dose dependent manner and induced apoptosis. Atropine attenuated immunosuppressive markers and M3R via inhibition of EGFR/AKT/ERK signaling pathways. However, 4-DAMP showed no effect on the expression of PD-L1, PD-L2, and choline acetyltransferase (ChAT) on CT-26 cells but attenuated M3R by suppressing the phosphorylation of AKT and ERK. Blocking of M3R in vivo decreased tumor growth and expression of immunosuppressive, cholinergic, and angiogenic markers through inhibition of AKT and ERK, leading to an improved immune response against cancer. The expression of immunosuppressive and cholinergic markers may hold potential in determining prognosis and treatment regimens for colorectal cancer patients. This study’s results demonstrate that blocking M3R has pronounced antitumor effects via several mechanisms, including inhibition of immunosuppressive molecules, enhancement of antitumor immune response, and suppression of tumor angiogenesis via suppression of the AKT/ERK signaling pathway. These findings suggest a crosstalk between the cholinergic and immune systems during cancer development. In addition, the cholinergic system influences cancer evasion from the host’s immunity.     

Relative Contribution of Blood Pressure and Renal Sympathetic Nerve Activity to Proximal Tubular Sodium Reabsorption via NHE3 Activity

We examined the effects of an acute increase in blood pressure (BP) and renal sympathetic nerve activity (rSNA) induced by bicuculline (Bic) injection in the paraventricular nucleus of hypothalamus (PVN) or the effects of a selective increase in rSNA induced by renal nerve stimulation (RNS) on the renal excretion of sodium and water and its effect on sodium-hydrogen exchanger 3 (NHE3) activity. Uninephrectomized anesthetized male Wistar rats were divided into three groups: (1) Sham; (2) Bic PVN: (3) RNS + Bic injection into the PVN. BP and rSNA were recorded, and urine was collected prior and after the interventions in all groups. RNS decreased sodium (58%) and water excretion (53%) independently of BP changes (p < 0.05). However, after Bic injection in the PVN during RNS stimulation, the BP and rSNA increased by 30% and 60% (p < 0.05), respectively, diuresis (5-fold) and natriuresis (2.3-fold) were increased (p < 0.05), and NHE3 activity was significantly reduced, independently of glomerular filtration rate changes. Thus, an acute increase in the BP overcomes RNS, leading to diuresis, natriuresis, and NHE3 activity inhibition.     

钢水喷镁精炼及其对钢性能的影响

由于镁对钢的脱氧、脱硫、净化钢水及转变夹杂物形态的良好作用,近年来许多冶金工作者致力于加镁精炼钢水的研究工作,但因在冶金温度下镁的蒸汽压很高,而其在钢水的溶解度又极小,加入困难,这方面的研究多归于失败。本文利用阿亨大学热力学数据库计算了以氩作为载气喷镁的脱氧、脱硫作用,以及压力和氩量对其影响,通过实验制定了行之有效的喷吹工艺,选择了合适的控制参数。
在1-3大压下,氩量为0.1-0.3N.L/m:n,可以向钢水成功地喷入镁。经过镁精炼的钢水,氧含量可降至4ppm,硫含量降至10ppm,氧化物及硫化物的评级均为0级,其尺寸均在5μm之下。随着喷镁量的增加(钢水重量的0.062至%0.56%),夹杂物中镁的氧化物及硫化物量增加,夹杂物总量减少且呈球形,此种夹杂物在热形变中不变形。因此在通常材料中所存在的各向异性完全消失,特别是缺口冲击韧性横向性能值提高了2~3倍。文章对材料在不同温度下的冲击韧性、过渡温度及断口夹杂物的形态进行了研究和论述。     

氮在渣-钢间传质系数的测定

使用Al₂O₃坩埚在真空感应炉内测定了1600℃时氮在含C还原渣和钢液之间的总传质系数β_o.研究表明,β_o与气相中氮分压P_N2的大小有关,随着P_N2的增加β_o增大.由物料平衡计算得出,在本实验条件下,β_o为3.7×10^-4 cm/S.     

Study of the Effect of Vibration Treatment of Porous Sintered Workpiece Treatment on Structure and Properties of Hot-Forged Powder Object Surface Layer

Metallurgist - A number of combine-harvester components are produced by mass production of hot-forged sintered powder blanks in the at “Rostsel’mash” plant. With the aim of...     

Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery

A key challenge for stem cell therapies is the delivery of therapeutic cells to the repair site. Magnetic targeting has been proposed as a platform for defining clinical sites of delivery more effectively. In this paper, we use a combined in vitro experimental and mathematical modelling approach to explore the magnetic targeting of mesenchymal stromal cells (MSCs) labelled with magnetic nanoparticles using an external magnet. This study aims to (i) demonstrate the potential of magnetic tagging for MSC delivery, (ii) examine the effect of red blood cells (RBCs) on MSC capture efficacy and (iii) highlight how mathematical models can provide both insight into mechanics of therapy and predictions about cell targeting in vivo. In vitro MSCs are cultured with magnetic nanoparticles and circulated with RBCs over an external magnet. Cell capture efficacy is measured for varying magnetic field strengths and RBC percentages. We use a 2D continuum mathematical model to represent the flow of magnetically tagged MSCs with RBCs. Numerical simulations demonstrate qualitative agreement with experimental results showing better capture with stronger magnetic fields and lower levels of RBCs. We additionally exploit the mathematical model to make hypotheses about the role of extravasation and identify future in vitro experiments to quantify this effect.     

Shear analysis of rice husk ash (RHA) reinforced tin-0.7-copper composite solders on electroless nickel/immersion silver (ENIAg) surfaces

In this study, the mechanical performance of the rice husk ash-reinforced tin-0.7 copper composite solder was investigated. 0.01 wt.%, 0.05 wt.% and 0.1 wt.% of rice husk ash (RHA) were added to the solder matrix to prepare the composite solders. In order, to replace the costly electroless nickel immersion gold surface finish on the copper substrate, the effect of electroless nickel immersion silver (ENIAg) as the surface finish was studied. The differential scanning calorimetry (DSC) analysis showed that the composite solder exhibited lower melting temperature relative to the plain solder owing to the inclusion of rice husk ash. Shear strength analysis was carried out to investigate the influence of rice husk ash and electroless nickel immersion silver surface finish on the shear strength of the developed composite solders. The results proved that the rice husk ash failed to enhance the shear strength of tin-0.7 copper lead-free solder with the plain solder exhibiting the highest shear strength.     

Processes for the Preparation of High-Purity Arsenic and Its Compounds

Inorganic Materials - This paper presents results of analysis of the patent, scientific, and technical literature concerned with the physicochemical and technological foundations of the preparation...