Acupuncture enhances anticancer effects of cyclophosphamide on 4T1 tumors via suppression of angiogenesis in BALB/c mice

Objective:Acupuncture is considered an important part of the alternative medical treatment of tumors.However,it is still unclear whether acupuncture has a direct effect on inhibition of tumor growth.The purpose of this study was to evaluate the effects of acupuncture treatment on tumors in BALB/c mice that were or were not administered cyclophosphamide.Methods:A 4T1 breast carcinoma mouse model for this study was established.When the mice developed 5 mm × 5 mm visible subcutaneous tumors,they were subjected to acupuncture and/or cyclophosphamide (CTX) treatment for 15 days.Results:Acupuncture and CTX treatment both reduced the size of the solid tumors.When used in conjunction,the tumor size reduction was even more obvious.Hematoxylin and eosin staining showed that acupuncture had a significant effect on induction of tumor cell necrosis and inhibition of angiogenesis.Immunohistochemistry showed that the expression of CD34 and matrix metalloproteinase-9 (MMP-9),which were related to angiogenesis,decreased after treatment with either acupuncture or CTX.However,when the two treatments were used in conjunction,they showed a synergistic effect on inhibiting the expression of CD34.However,the synergistic effect was not observed onMvMP-9 expression.Conclusion:Acupuncture plays an important role in improving the effect of chemotherapy by inhibiting angiogenesis.

In Vivo Animal Model Evaluation of a Powerful Oral Nanomedicine for Treating Breast Cancer in BALB/c Mice Using 4T1 Cell Lines without Chemotherapy

Nanopharmaceuticals containing quantum dot nanoparticles (Q-Dot NPs) for treating serious cancers such as breast cancer have made fantastic proposals. In this study, ZnO quantum dot NPs are formulated via ZnO@PVP nanopolymer as co-assistants coordinating with efficacious suitable wetting agents, PEG-binding compound, and W/O emulsifier for producing eco-friendly water-based nanodrug. Several characterization techniques containing SEM, TEM, FTIR, photoluminescence, zeta potential, and UV-Vis absorption were employed for ZnO Q-Dot NPs in nanodrug. This work aims to investigate the anti-tumor effects of such nanomedicine on the 4T1 breast cancer cell line in BALB/c mice, being elaborated through intraperitoneal, injection (IVP) and oral therapy. The impressive findings showed that ZnO nanodrug caused changes in blood factors, having the most effectiveness at 40 μg/ml concentration after two weeks of oral treatments. The significant increase in white blood cells (WBC) neutrophils and meaningful decreases in lymphocytes and especially cholesterol were powerful simultaneous impacts, successfully treating malignant breast cancer masses. In this significant animal model research for breast cancer, the sick mice recovered entirely and even had a safe space to mate. Histopathological results showed no evidence of breast tumor formation or metastasis in the group treated with nanodrug and their children. This nanomedicine has a therapeutic effect, and is ready to be applied for treating volunteer breast cancer patients. However, its prevention (inhibitory) effect can also be analyzed and added to current data in future studies.

Anti-breast cancer properties and toxicity of Dillenia suffruticosa root aqueous extract in BALB/c mice

Objective:To determine the anti-breast cancer activities and the safety oral consumption of Dillenia suffruticosa root aqueous extract(DRAE)in BALB/c mice.Methods:In the anti-breast cancer study,female BALB/c mice were divided into five groups(n=12),which were(1)positive control(with breast cancer,untreated),(2)negative control(without breast cancer,untreated)and other three groups of mice with breast cancer treated with 1 000,500 and 250 mg/kg of DRAE,respectively,by oral gavage for 28 days.All mice except from the negative control group were injected into the mammary fat pad with 4T1 cells(1×1054T1 cells/0.1 m L of phosphate buffer solution).DRAE was administered orally on Day 11 after the tumor has developed.Results:The tumor volume of the 1 000 mg/kg of DRAE group reduced significantly compared to the positive control while treatment with 500 mg/kg of DRAE had significantly inhibited metastasis to the heart.In the acute toxicity study,treatment with up to5 000 mg/kg of DRAE was not toxic to the animals,indicating its safety when a large amount of this plant extract was ingested.Based on the sub-acute toxicity study,treatment of the highest dose of DRAE(1 000 mg/kg)had mild liver toxicity indicated by mild focal hemorrhage.Conclusions:DRAE possesses anti-breast cancer properties but at the same time it shows mild toxicity to the liver.The non observable adverse effect dose for DRAE is500 mg/kg.

A tale of motor neurons and CD4＋ T cells： moving forward by looking back

Amyotrophic lateral sclerosis （ALS） is a fatal progressive disorder characterized by the selective degeneration of motor neurons （MN）. The impact of peripheral immune status on disease progression and MN survival is becoming increasingly recognized in the ALS research field. In this review, we briefly discuss findings from mouse models of peripheral nerve injury and immunodeficiency to understand how the immune system regulates MN survival. We extend these observations to similar studies in the widely used superoxide dismutase 1 （SOD1） mouse model of ALS. Last, we present future hypotheses to identify potential causative factors that lead to immune dysregulation in ALS. The lessons from preceding work in this area offer new exciting directions to bridge the gap in our current understanding of immune mediated neuroprotection in ALS.

Transgenic 4-1BBL-engineered vaccine stimulates potent Gag-specific therapeutic and long-term immunity via increased priming of CD44＋CD62Lhigh IL-7R＋ CTLs with up- and downregulation of anti- and pro-apoptosis genes

Human immunodeficiency virus type-1 （HIV-1）-specific dendritic cell （DC） vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo vaccine stimulated Gag-specific effector CD8＋ cytotoxic T lymphocyte （CTL） responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus （AdV）4-1BBL, which expressed mouse 4-1BB ligand （4-1BBL）, and generated transgenic 4-1BBL-engineered OVA-Texo/4.1BSL and Gag-Texo/4.1BSL vaccines by transfecting ovalbumin （OVA）-Texo and Gag-＇rexo cells with AdV4.1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/4.ZSSL vaccine stimulates more efficient OVA-specific CTL responses （3.26%） compared to OVA-Texo-activated responses （1.98%） in wild-type C57BIJ6 mice and the control OVA-TeXO/Nu, vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing B16 melanoma BL6-1OovA cells. OVA-Texo/4.1BBL-stimulated CTLs, which have a CD44＋CD62Lhigh IL-7R＋ phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-1OovA melanoma. In addition, we demonstrate that OVA-Texo/4_ZBBL-Stimulated CTLs up- and downregulate the expression of anti-apoptosis （Bcl2110, Naipl, No13, Pak7 and Tnfrsfllb） and pro-apoptosis （Casp12, Trp63 and Trp73） genes, respectively, by RT2 Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4.1BBL vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing B 16 melanoma BL6-1OGag/A2 cells than the control Gag-TeXO/NuH vaccine in transgenic HLA-A2 mice. Taken together, our novel Gag-Texo/4-ZBBL vaccine, which is capable of stimulating potent Gag-specific therapeutic and long-term immunity, may represent a new immunotherapeutic vaccine for controlling HIV-1 infection.

银连祛风汤对慢性荨麻疹模型小鼠免疫指标的影响

目的探讨银连祛风汤对慢性荨麻疹模型小鼠免疫指标的影响。方法将72只小鼠(雌雄各半)分为正常组(A组),模型组(B组),银连祛风汤低、中、高剂量组[C_1组、C_2组、C_3组生药18.35,36.70 55.05 g/(kg·d)],阳性药对照组[D组地氯雷他定0.83 mg/(kg·d)],各12只。第1天和第10天,除A组外其余各组小鼠均腹腔注射卵白蛋白+氢氧化铝悬液的混合液,以建立慢性荨麻疹小鼠模型。C_1组、C_2组、C_3组、D组小鼠于第1次免疫注射后的第6天灌胃给予相应剂量药物,每日1次;A组、B组小鼠灌胃等体积生理盐水。各组小鼠均连续给药21 d。采用双抗体酶联免疫吸附法检测小鼠血管壁组织匀浆上清液和血清中单核细胞趋化蛋白-1(MCP-1)、嗜酸性粒细胞趋化因子(Eotaxin)、白细胞介素4(IL-4)水平;采用流式细胞仪检测T淋巴细胞亚群CD_4~+和CD_8~+细胞阳性率。结果与A组比较,B组小鼠血管壁组织匀浆上清液和血清中MCP-1,Eotaxin,IL-4水平及CD_8~+细胞阳性率均显著升高(P <0.01),CD_4~+细胞阳性率和CD_4~+/CD_8~+比值均显著降低(P<0.01);与B组比较,C_1组、C_2组、C_3组、D组小鼠血管壁组织匀浆上清液和血清中MCP-1,Eotaxin,IL-4水平均显著降低,C_3组和D组小鼠CD_4~+细胞阳性率和CD_4~+/CD_8~+比值均显著升高(P <0.05);与C_1组比较,C_3组小鼠上述指标变化显著(P<0.05)。结论银连祛风汤能显著降低慢性荨麻疹模型小鼠MCP-1,Eotaxin,IL-4水平和CD_8~+细胞阳性率升高CD_4~+细胞阳性率。