Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.     

新化合物Elixir-X对肝切及辐射所致衰老小鼠的抗衰老作用

目的 探讨蜂巢提取物Elixir-X对自然衰老及辐射衰老小鼠的影响，为Elixir-X的进一步研发提供药理学基础。方法 采用小鼠肝脏切除术建立自然衰老小鼠模型，将其分为空白对照组、Elixir-X组、白藜芦醇组及模型组，连续给药7 d后，检测小鼠70%肝脏切除后的再生过程中，衰老细胞、肝脏功能恢复与肝脏再生的变化，观察Elixir-X对自然衰老的影响；采用60CO辐射法建立辐射衰老小鼠模型，将其分为模型组、空白对照组、白藜芦醇组、Elixir-X高、低剂量组，通过检测小鼠肠隐窝干细胞再生、小肠绒毛结构以及衰老细胞的变化，对比不同剂量Elixir-X对辐射后衰老的影响。结果 在肝脏切除术的小鼠模型中，Elixir-X组的肝功能水平明显低于模型组的肝脏自然再生小鼠，显著促进了肝功能恢复（P＜0.05）；同时与模型组相比，Elixir-X组清除了肝脏切除后再生过程中产生的衰老细胞（P＜0.05），Ki-67的着色斑块明显增加，促进肝脏的再生，且肝血窦的扫描电镜影像结果中Elixir-X组肝血窦再生加快。60CO辐照小鼠模型中，与模型组相比，Elixir-X组有效促进辐照后肝脏功能恢复（P＜0.05），Elixir-X高剂量组体重也恢复到正常水平，与空白对照组无显著差异；与模型组相比，Elixir-X低剂量组小肠的β-Gal着色细胞减少，Elixir-X高剂量组甚至能更有效地减少衰老细胞（P＜0.05）；小肠HE染色的结果中，Elixir-X组小肠绒毛结构得到恢复；Ki-67的IHC染色中，与模型组相比，Elixir-X组着色板块更多，且着色区域都在肠隐窝干细胞位置。结论 Elixir-X能有效清除肝脏切除术引起的自然衰老与辐射引起的损伤性衰老细胞，对衰老具有显著地抑制作用。     

Semi-perfusion cultures of suspension MDCK cells enable high cell concentrations and efficient influenza A virus production

Control and prevention of rapid influenza spread among humans depend on the availability of efficient and safe seasonal and pandemic vaccines, made primarily from inactivated influenza virus particles. Current influenza virus production processes rely heavily on embryonated chicken eggs or on cell culture as substrate for virus propagation. Today’s efforts towards process intensification in animal cell culture could innovate viral vaccine manufacturing using high-yield suspension cells in high cell density perfusion processes. In this work, we present a MDCK cell line adapted to grow as single cell suspension with a doubling time of less than 20 h, achieving cell concentrations over 1 × 10⁷ cells/mL in batch mode. Influenza A virus titer obtained in batch infections were 3.6 log₁₀(HAU/100 µL) for total- and 10⁹ virions/mL for infectious virus particles (TCID₅₀), respectively. In semi-perfusion mode concentrations up to 6 × 10⁷ cells/mL, accumulated virus titer of 4.5 log₁₀(HAU/100 µL) and infectious titer of almost 10¹⁰ virions/mL (TCID₅₀) were possible. This exceeds results reported previously for cell culture-based influenza virus propagation by far and suggests perfusion cultures as the preferred method in viral vaccine manufacturing.     

Anti-Oxidant,Anti-Hemolytic Effects of Crataegus aronia Leaves and Its Anti- Proliferative Effect Enhance Cisplatin Cytotoxicity in A549 Human Lung Cancer Cell Line

Objective: For Arabian traditional medicine, Crataegus aronia syn. Azarolus (L) Bosc. ex DC (Rosaceae) is widely used to treat diabetes, sexual weakness, cardiovascular diseases and cancer. The anti-cancerous and anti-hemolysis effects of the hydroalcoholic extract of this plant have never been investigated before. The present study aims to evaluate the biological activities of the hydroalcoholic extract of Crataegus aronia leaves in combination with cisplatin, one of the most widely employed chemotherapeutics, on A549 human lung cancer cell line. Methods: The anti-oxidant and anti-proliferative activities of leaves, fruits, seeds of C. aronia were investigated by DPPH method and MTT assay; respectively. Cell migration activity was investigated by wound healing and by cell aggregation assays. The effect of C. aronia in inducing cell cycle arrest along with activating cell apoptosis was evaluated by flow cytometry and Western blot assays, respectively. Results: Our results showed that C. aronia leaves (C. aronia L.) had the highest anti-oxidant and anti-proliferative activities. The leaves extract was potent against hemolysis of the human erythrocytes and showed elevated decrease in migration by reducing wound healing migration and by increasing cell aggregation. Finally, C. aronia L. treatment exhibited apoptotic activity on A549 cells by the down-regulation of PARP-1, caspase-3 and Bcl-2 proteins and by increasing the percentage of A549 cells in sub G0 cell cycle. Moreover, the co-treatment of C. aronia L. and cisplatin remarkably sensitised A549 cells to cisplatin. Conclusion: The results suggested that C. aronia L. could be used as a potential treatment against human lung cancer exhibiting minimal side effects on human health.     

Comparison of Salivary and Serum Alkaline Phosphates Level and Lactate Dehydrogenase Levels in Patients with Tobacco Related Oral Lesions with Healthy Subjects - A Step Towards Early Diagnosis

Aim: To evaluate and compare salivary and serum levels of Alkaline Phosphates and Lactate Dehydrogenase in patients without the habit of tobacco, in patients with the habit of tobacco, in patients with benign oral lesions and in patients with oral premalignant lesions and oral malignant lesions. Material and Methodology: This study was comprised of 500 subjects, Group I: 100 healthy individuals without the habit of tobacco usage formed the control group. Group II: 100 patients with the habit of tobacco/ smoking consumption without any oral lesion. Group III: 100 patients with benign oral lesions. Group IV: 100 patients having the history of tobacco consumption and having apparent precancerous lesions like leukoplakia, erythroplakia. Group V:100  patients having frank oral cancer. The grade of dysplasia in these patients was statically correlated with the levels of serum and salivary ALP and LDH. Results: This study revealed that there was high expression of both serum and salivary ALP and LDH  in group IV and Group V as compared with the other groups and mean difference showed a statistically significant p value of less than 0.01. This study revealed that the in group V, the highest level of serum and salivary ALP was found in those patients who were reported with poorly differentiated oral cancer. Conclusion: Both Alkaline phosphates and Lactate dehydrogenase could be considered a sensitive markers for the detection of dysplasia with already existing precancancerous and cancerous lesions.     

Abscopal effect in radioimmunotherapy

Abscopal effect is an interesting phenomenon in radiobiology that causes activation of immune system against cancer cells. Traditionally, this phenomenon was known as a suppressor of non-irradiated tumors or metastasis. However, it can be used as a stimulator of the immune system against primary tumor during radiotherapy. Immunotherapy, a novel tumor therapy modality, also triggers immune system against cancer. To date, some immunotherapy types have been developed. However, immune checkpoint blockade is a more common modality and some drugs have been approved by the FDA. Studies have shown that radiotherapy or immunotherapy administered alone have low efficiency for tumor control. However, their combination has a more potent anti-tumor immunity. For this aim, it is important to induce abscopal effect in primary tumors, and also use appropriate drugs to target the mechanisms involved in the exhaustion of cytotoxic CD8+T lymphocytes (CTLs) and natural killer (NK) cells. Among the different radiotherapy techniques, stereotactic body radiation therapy (SBRT) with some few fractionations is the best choice for inducing abscopal effect. On the other hand, programmed cell death 1 (PD-1) is known as one of the best targets for triggering anti-tumor immunity. This combination is known as the best choice among various strategies for radioimmunotherapy. However, there is the need for other strategies to improve the duration of immune system’s activity within tumor microenvironment (TME). In this review, we explain the cellular and molecular mechanisms behind abscopal effect by radiotherapy and evaluate the molecular targets which induce potent anti-tumor immunity.     

2017年全国中医药健康文化知识普及情况调查数据分析

持续追踪与分析全国中医药健康文化知识普及情况变化趋势,为制定中医药健康文化知识普及有关政策、策略和措施提供科学依据。该研究采用分层多阶段结合随机抽样方法,对全国(不包含西藏自治区和港、澳、台地区)30个省(自治区、直辖市)328个调查点15~69岁常住人口进行入户调查。研究采用《2017年全国中医药健康文化知识普及情况调查问卷》对调查对象接触、认知、信任和使用中医药健康文化知识的情况进行问卷调查。该研究共调查89 107人,有效问卷87 287份,有效率97.96%;其中城市人口占51.35%,农村人口占48.65%;男性占48.25%,女性占51.75%。2017年全国中医药健康文化知识普及率91.72%,阅读率89.61%,信任率89.60%,行动率55.53%。研究发现,年轻群体、高文化程度居民、未患慢性病群体的中医药健康文化知识普及情况更优。建议加强针对重点地区、重点人群的中医药健康文化普及工作,针对不同地区人群开展差异化中医药健康教育,内容与形式相结合,打好大众媒体组合拳。