Potential of four marine-derived fungi extracts as anti-proliferative and cell death-inducing agents in seven human cancer cell lines

Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.

Clinical Study on Ganbi Decoction (肝痹汤) in Treating Antituberculotic Agent-Caused Liver Injury

Objective： To study the effect and mechanism of Ganbi decoction （GBD, 肝痹汤 ） in treating patients with antituberculotic agent caused liver injury （ATB-LI）. Methods： One hundred and twenty-eight patients with ATB-LI were randomly assigned to the treated group （ n = 66） and the control group （ n = 62） with the envelop method. Meanwhile, 60 healthy persons were selected as the healthy control group. The treated group was treated by GBD one dose every day with the constituents modified depending on patients＇ symp- toms, and the control group was treated with glucuronolactone tablets and inosine injection. One week was taken as one treatment course. The changes of clinical syndromes, physical signs, T-lymphycyte sub-groups and serum level of nitric oxide （NO） were observed before and after treatment and the recovery time of liver function was recorded. The outcome was compared with that in the healthy control group. Results： In the treated group, 28 patients （42.4%） were cured, 30 （45.5%） improved and 8 （ 12.1% ） ineffectively cured, the total effective rate being 87.9% （58/66）. In the control group, 17 patients （27.4%） were cured, 24 （38.7%） improved, and21 （33.9%）ineffectively cured, the total effective rate being 66.1% （41/62）. The total effective rate in the treated group was significantly higher than that in the control group （ P〈0. 05）. Liver function was improved in both groups, recovery time in the treated group was 12.0±7.0 days, which was significantly shorter than that in the control group （16.0±8.0 days）, showing significant difference between the two groups （ P〈0.05）. The levels of CD3, CD4 and CD8 were significantly higher and level of NO significantly lower in the two groups of patients than those in the healthy control group （ P〈0. 05）, but these parameters were improved more significantly in the treated group after treatment, when compared with those before treatment or with those in the control group, all showing significant difference （P〈0.05）. Conclusion： GBD could prevent ATB-LI, and its mechanism could be by way of reducing NO production induced by endotoxin of macrophage and stimulating the proliferation of T-lymphycyte to elevate immunity.

Intravitreal anti-VEGF agents, oral glucocorticoids, and laser photocoagulation combination therapy for macular edema secondary to retinal vein occlusion: preliminary report

AIM： To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor （VEGF） agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema （ME） secondary to retinal vein occlusion （RVO）. METHODS： This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity （BCVA）, central retinal thickness （CRT）, and retinal vessel oxygenation were examined over 12mo. RESULTS： Patients received 1.43＋0.81 anti-VEGF injections. Mean baseline and 12-month IogMAR BCVA were 0.96±0.51 （20/178） and 0.31±0.88 （20/40）, respectively, in eyes with central retinal vein occlusion （CRVO） （P〈0.00）, and 1.02±0.45 （201209） and 0.60±0.49 （20/80）, respectively, in eyes with branch retinal vein occlusion （BRVO） （P〈0.00）. At 12mo, CRT had significantly decreased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. Venous oxygen saturation had significantly increased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. No examined parameters were significantly different between the 2 RVO groups. No serious adverse effects occurred. CONCLUSION： Anti-VEGF, glucocorticoid, and photocoagulation combination therapy improves visual outcome, prolongs therapeutic effect, and reduces the number of intravitreal injections in eyes with RVO- associated ME.

Effect of K1, K2 Anti-Bacterial Agents on Tobacco Ralstonia Solanacearum

The tobacco Ralstonia Solanacearum were both cultured on nutrient agar plates and inoculated in seedling stage of tobacco, then treated with K1 and K2, two anti-bacterial agents, at a serial con-centrations to study their inhibitory efficiency. The result indicated that K1 can inhibit R. Solanacearum growth entirely, at the concentration range from 1/50 to 1/5000. K2 can reach the same result at the concentration range from 1/50 to 1/50000. Compared with the control plates, K1, at the concentration 1/50000, had no significant differences, and the average number of colony per plate was 112-115. The immature tobacco shown wilt as soon as inoculated with R. Solanacearum, and recovered gradually after using K1, K2. The densities of microbial suspension, handled by K1, K2 within 10 hs, were both significantly lower than the controlled ones. The optical microscopy also shown that handled microbial body differed from the controlled, whose body was regular short, rod shape as opposed to the handled ones with irregular rod shape and damaged body. All the results indicated that K1 and K2 both had inhibitory effects on tobacco R. Solanacearum, and K2 was more efficient than K1.

Novel anti-diabetic agents in non-alcoholic fatty liver disease: a mini-review

BACKGROUND:Non-alcoholic fatty liver disease(NAFLD)encompasses a spectrum that ranges from simple steatosis to non-alcoholic steatohepatitis(NASH)and to cirrhosis.The recommended treatment for this disease includes measures that target obesity and insulin resistance.The present review summarizes the role of newer anti-diabetic agents in treatment of NAFLD.DATA SOURCES:PubMed,MEDLINE and Ovid databases were searched to identify human studies between January 1990and January 2013 using specified key words.Original studies that enrolled patients with a diagnosis of NAFLD or NASH and involved use of newer classes of anti-diabetic agents for a duration of at least 3 months were included.RESULTS:Out of the screened articles,four met eligibility criteria and were included in our review.The classes of newer anti-diabetic medications described were dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 analogues.CONCLUSIONS:Liraglutide and Exenatide showed improvement in transaminases as well as histology in patients with NASH.Sitagliptin showed improvement in transaminases but limited studies are there to access its effect on histology.Further studies are needed to support use of newer anti-diabetic medications in patients with NAFLD.

Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy

Microvessels promote proliferation of tumor cells by delivering oxygen and nutrients, but rapid growth of tumors results in unmet demands for oxygen and nutrients, thereby creating a hypoxia microenvironment. Under hypoxic conditions, vascular endothelial cells（ECs） initiate the formation of immature and abnormal microvasculature. This results in leakage and tortuosity that facilitates tumor cell invasion, metastasis and resistance to cytotoxic treatment.Radiotherapy（RT） is a vital tumor treatment modality. Currently, more than 60% of patients with malignant tumors receive RT at certain points during their treatment. Hypoxia induced by abnormal microvessels can hamper the cytotoxic effect of ionizing radiation, particularly, stereotactic body radiotherapy（SBRT）. Anti-angiogenesis（AA） agents are known to reduce and renormalize microvessels in tumors, and hence alleviate hypoxia. The combination of AA agents with SBRT may have a synergistic role in inhibiting the growth of tumors. On the contrary, large doses of irradiation may affect tumor microvessels itself. In this review, we aim to clarify the relationship between SBRT and microvessel formation in tumors. In addition, we provide a retrospective analysis of the combination therapy involving SBRT and AA agents in preclinical and clinical practice to define its role in antitumor treatment.

Era of direct acting anti-viral agents for the treatment of hepatitis C

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.

Anti-angiogenic agents in metastatic colorectal cancer

Colorectal cancer(CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various antiangiogenic agents in patients with metastatic CRC(m CRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in m CRC patients. Despite the discovery of several promising anti-angiogenic agents, m CRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients.

Toxicity Study of Anti-HABs Agents on Penaeus chinensis

In order to study the effect of anti-HABs agents on Penaeus chinensis, the toxicity experiments on clay, Ca(ClO)2, FeCl3, and AlCl3 to Penaeus chinensis are carried out. The results show that: (1) the clay isn't toxic to Penaeus chinensis; (2) Ca(ClO)2 has no toxicity to Penaeus chinensis at low levels, but has acute and chronic toxicity at high levels; (3) Penaeus chinensis can accumulate Fe and Al. The toxic effect needs further study.

Bridging academic science and clinical research in the search for novel targeted anti-cancer agents

This review starts with a brief history of drug discovery & development, and the place of Asia in this worldwide effort discussed. The conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. The importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. The most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. The factors to consider before starting a new drug discovery & development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials.

Synthesis and Evaluation of Quinolino-Benzoxaboroles as Potential Antimicrobial Agents

Several quinolino-benzoxaborole derivatives have been prepared to start from aminobenzoxaboroles. These derivatives have been evaluated for their anti-cancer activity on human and murine cancer cell lines and based on their relative non-toxicity, these compounds were further evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis. The synthesized compounds were also evaluated for antifungal activity in C. albicans and C. neoformans.

New innovation of moisturizers containing non-steroidal anti-inflammatory agents for atopic dermatitis

Atopic dermatitis is a chronic, relapsing and extremely pruritic eczematous disease which commonly affects children. The standard management consists of a combination of anti-inflammatory drugs in adjunctive with skin care management particular moisturizer application. A concern for the side effects associated with long term use of corticosteroids has also been considered. There has been an emerging interest in moisturizer containing non-steroidal anti-inflammatory agents such as herbal extracts, vitamins, mineral and lipids. The in vitro and the in vivo studies of each agent were reviewed. The clinical study on the efficacy of moisturizers containing these agents were also demonstrated including the author's studies and clinicalexperience. These moisturizers might be considered as an alternative treatment in acute flare of mild to moderate atopic dermatitis.

移动边缘计算下移动Agent的任务安全迁移策略

移动边缘计算中任务多在远离服务中心的边缘节点上执行,边缘节点的安全能力并不能得到保障,如何将任务迁移到安全可靠的边缘节点来执行是当前存在的一个问题。针对移动边缘计算下任务迁移中的安全风险问题,构建了适用于移动边缘计算环境的移动Agent安全风险计算模型,通过风险采集、风险处理和风险反馈综合评估边缘节点的抗风险值;并引入动态免疫算法,在任务计算和安全计算时间满足任务截止时间的前提下,实现任务迁移的安全能力最大化。仿真实验表明,相比于传统的任务迁移方案,该策略大大提高了移动边缘计算中任务迁移的抗风险能力,具有一定的鲁棒性。

Development of a SGJ-1 of Water-Based Anti-Wax Agent

The phenomenon of petroleum wax deposition is very common during oil well production. When the wax molecule condenses on the surface of the pipeline, it will hinder the exploitation of crude oil, reduce the recovery rate of crude oil, and may lead to the blockage of the pipeline when it is serious, so that the oil recovery work will stop. This phenomenon can be obviously changed by using wax cleaning agent. However, the low ignition point and toxicity of oil-based wax remover are not conducive to oil recovery. Therefore, a new water-based paraffin remover SGJ-1 was developed in this paper. The best formula is: wax dispersant 15%, wetting reversion agent 1%, sodium silicate 1%, alcohol cosolvent 8% and 75% water. Condensation point, wax dissolution rate and anti-wax performance of SGJ-1 water-based dewaxing and anti-waxing agent were tested by self-assembly testing device. The experimental results show that the condensation point of SGJ-1 is -34°C, the viscosity reduction effect is good under 35°C, and the wax dissolution rate is 0.0512 g/min, The highest wax prevention rate can reach 89.58% and the wax removal and wax prevention ability is excellent. Compared with other paraffin removers, SGJ-1 can also reduce the viscosity of crude oil, so it has a good development prospect.

复方红藤糖浆联合抗菌药物治疗盆腔炎性疾病的效果

目的探讨复方红藤糖浆联合抗菌药物治疗盆腔炎性疾病(PID)患者的效果及安全性。方法选取2018年1月至2021年12月安徽中医药大学第一附属医院妇科收治入院的60例PID患者为研究对象,按随机数字表法分为研究组和对照组,各30例。2组采用盐酸头孢替安联合奥硝唑氯化钠注射液静脉输注治疗,研究组同时予复方红藤糖浆口服,2组均治疗1周。比较2组患者临床疗效、疼痛视觉模拟评分(VAS)、盆腔痛客观体征(McCormack)评分、下腹疼痛、腰骶疼痛、带下异常、乏力中医症候积分、白细胞计数(WBC)、超敏C反应蛋白(hs-CRP)、白细胞介素(IL)-10、肿瘤坏死因子(TNF)-α。结果治疗后,研究组及对照组的总有效率分别为93.33%及73.33%;研究组总有效率高于对照组,差异有统计学意义(P<0.05)。与治疗前相比较,2组治疗后VAS评分、McCormack评分、下腹疼痛积分、腰骶疼痛积分、带下异常积分、乏力积分、WBC、hs-CRP、TNF-α降低,IL-10升高(P均<0.01)。与对照组治疗后相比较,研究组治疗后VAS评分、McCormack评分、下腹疼痛积分、腰骶疼痛积分、带下异常积分、乏力积分、WBC、hs-CRP、TNF-α降低,IL-10升高(P均<0.05)。结论复方红藤糖浆联合抗菌药物可改善湿热蕴结证盆腔炎患者临床症状,疗效明显。

高效液相色谱法测定洗发护发产品中18种防腐剂和去屑剂

建立高效液相色谱法(HPLC)同时测定不同基质化妆品中18种防腐剂和去屑剂组分的含量,并对50批市售洗发护发类化妆品进行质量分析。不同基质样品经前处理提取后,采用HPLC法分析,外标法定量。选取C18色谱柱(4.6 mm×250 mm,5μm),甲醇和磷酸二氢钠水溶液(pH调节至3.8)作为流动相,进行梯度洗脱,流速为1.0 mL/min,柱温30℃,选取二极管阵列检测器多波长分析。18种组分在色谱图中分离度良好,峰面积与质量浓度在0.4~600μg/mL范围内呈良好的线性关系(r>0.9983),检出浓度在0.4~10 mg/kg之间。多种组分平均回收率(n=6)为83.1%~110.4%,RSD为0.12%~7.6%,回收率良好;多种组分在24 h内保持稳定,RSD在0.15%~3.8%之间,稳定性良好。50批样品中检出9种成分,吡硫鎓锌、吡罗克酮乙醇胺盐、对氯间甲酚、氯咪巴唑、三氯生、水杨酸的含量分别为2100~6800,39~2900,130~370,24~1600,0.14~0.19,28~1900 mg/kg。苄氯酚、邻氨基苯酚、邻伞花烃-5-醇的含量检出但是含量小于定量限,无法准确定量。该方法经方法学验证,可同时测定化妆品中18种防腐剂和去屑剂组分的含量。

靶向胰岛素样生长因子系统抗肿瘤治疗的研究进展

胰岛素样生长因子(IGF)系统由配体、受体、结合蛋白组成。其中,配体主要有IGF-1、IGF-2和胰岛素,通过与特定的受体结合来发挥作用;涉及受体主要有Ⅰ型IGF受体(IGF-1R)、Ⅱ型IGF受体(IGF-2R)、胰岛素受体(IR)和IGF-1R与IR的杂合受体;此外,IGF系统还包括6种高亲和力IGF结合蛋白(IGFBP-1~6)。IGF系统不仅在调节人体重要生理过程(如细胞生长、分化以及新陈代谢等)方面具有关键作用,其各组分表达水平的变化还在肿瘤的发生发展中发挥重要作用。近些年的研究显示,靶向IGF系统的各个组分或其相关信号通路有助于阻断肿瘤的发生发展并对后续肿瘤治疗产生有益作用。本文综述了IGF系统的各组分及相关信号通路在肿瘤中的作用,以及目前靶向IGF系统各组分的抗肿瘤药物研究情况,并分析了靶向IGF系统在肿瘤治疗中遇到的问题,以期为靶向IGF系统的抗肿瘤药物研究提供思路。

决奈达隆联合美托洛尔应用于老年房性心律失常患者的疗效观察

目的 探讨决奈达隆联合小剂量美托洛尔治疗快速性房性心律失常的疗效。方法 选取2020年1月至2022年1月江苏省苏北人民医院收治的老年快速性房性心律失常患者160例,按照掷币法随机分为决奈达隆组57例、美托洛尔组55例和联合(决奈达隆+美托洛尔)组48例。比较3组用药前后心律失常发作次数、持续时间及症状变化等发生情况。结果 用药3个月和6个月后,联合组总有效率显著高于决奈达隆组和美托洛尔组,差异有统计学意义(P<0.05)。用药6个月后,联合组心房颤动(AF)发作次数[(2.31±1.78)次/48 h vs(11.56±18.68)次/48 h]、AF持续时间[(4.86±6.73)h/48 h vs(10.92±9.61)h/48 h]、心房扑动(AFL)发作次数[(2.33±1.53)次/48 h vs(4.33±1.53)次/48 h],AFL持续时间[(5.15±4.87)h/48 h vs(21.54±20.08)h/48 h]少于用药前,决奈达隆组AFL持续时间[(2.75±1.94)h/48 h vs(10.29±8.04)h/48 h]明显少于用药前,差异有统计学意义(P<0.05)。结论 决奈达隆联合小剂量美托洛尔治疗快速性房性心律失常不仅能明显改善症状,还能显著减少房性期前收缩、房性心动过速发作次数,减少AF、AFL的发作次数及持续时间,可有效控制心率。

二氧化硅开口剂在流延聚丙烯薄膜中的应用及开口机理

使用4种二氧化硅(SiO_(2))开口剂及一种进口开口剂AB905,通过双螺杆挤出机在相同的加工条件下制备了5种流延聚丙烯膜(CPP)/SiO_(2)母粒并流延成膜。结果表明,5种开口剂都能满足CPP膜的防粘开口性能要求,动/静摩擦系数均降到0.12以内(属于高爽滑性)。50℃,7 kPa负载下压制24 h的抗粘连性测试表明,K45和AB905制成的CPP膜间均没有任何粘连,而纯PP膜有一定的粘连。原子力显微镜分析表明,亚微米级SiO_(2)开口剂粒子附近都存在凹坑,这些凹坑对降低负压、减小范德华力从而降低PP薄膜的粘连起到了非常关键的作用。最后,根据实验数据首次提出了一种适用于CPP膜的防粘连与开口原理模型,有望为生产更高防粘开口效率的开口剂提供参考。