Review of the Applications of Biomedical Compositions Containing Hydroxyapatite and Collagen Modified by Bioactive Components

Regenerative medicine is becoming a rapidly evolving technique in today’s biomedical progress scenario. Scientists around the world suggest the use of naturally synthesized biomaterials to repair and heal damaged cells. Hydroxyapatite (HAp) has the potential to replace drugs in biomedical engineering and regenerative drugs. HAp is easily biodegradable, biocompatible, and correlated with macromolecules, which facilitates their incorporation into inorganic materials. This review article provides extensive knowledge on HAp and collagen-containing compositions modified with drugs, bioactive components, metals, and selected nanoparticles. Such compositions consisting of HAp and collagen modified with various additives are used in a variety of biomedical applications such as bone tissue engineering, vascular transplantation, cartilage, and other implantable biomedical devices.     

Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes

Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.     

A Bioluminescent Biosensor for Quantifying the Interaction of SARS-CoV-2 and Its Receptor ACE2 in Cells and In Vitro

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus–host interactions in order to quickly evaluate the infectious ability of mutant viruses and to develop or validate virus-inhibiting drugs. Here, we developed an ultrasensitive bioluminescent biosensor to evaluate virus–cell interactions by quantifying the interaction between the SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid, and HTP biosensor tool will significantly expedite the detection of viral mutants and the anti-COVID-19 drug discovery process.     

Clinical inertia in patients with type 2 diabetes treated with oral antidiabetic drugs: Results from a Japanese cohort study (JDDM53)

Aims/IntroductionTreatment intensification is commonly delayed in people with type 2 diabetes, resulting in poor glycemic control for an unacceptable length of time and increased risk of complications.Materials and MethodsThis retrospective study investigated clinical inertia in 33,320 Japanese adults with type 2 diabetes treated with oral antidiabetic drugs (OADs) between 2009 and 2018, using data from the Computerized Diabetes Care (CoDiC^®) database.ResultsThe median time from first reported glycated hemoglobin (HbA1c) ≥7.0% (≥53 mmol/mol) to treatment intensification was considerably longer and HbA1c levels were higher the more OADs the patient was exposed to. For patients receiving three OADs, the median times from HbA1c ≥7.0% (53 mmol/mol) to intensification with OAD, glucagon‐like peptide‐1 receptor agonist or insulin were 8.1, 9.1 and 6.7 months, with a mean HbA1c level at the time of intensification of 8.4%, 8.9% and 9.3%, respectively. The cumulative incidence for time since the first reported HbA1c ≥7.0% (≥53 mmol/mol) to intensification confirmed the existence of clinical inertia, identifying patients whose treatment was not intensified despite poor glycemic control. HbA1c levels ≥7.0% (≥53 mmol/mol) after ≥6 months on one, two or three OADs were observed in 42%, 51% and 58% of patients, respectively, showing that approximately 50% of patients are above HbA1c target regardless of how many OADs they take.ConclusionsReal‐world data here show clinical inertia in Japanese adults with type 2 diabetes from early diabetes stages when they are receiving OADs, and illustrate a need for earlier, more effective OADs or injectable treatment intensification and better communication around the existence of clinical inertia.     

Targeting ageing and preventing organ degeneration with metformin

BackgroundAgeing is characterized by a decline in cognitive and bodily functions. Metformin, the most commonly prescribed antidiabetic agent today, has proved to be able to modulate oxidative stress, several inflammatory pathways and cellular senescence to promote anti-ageing. This review aims to explore and summarize the effects of metformin on ageing.ResultsMetformin, a longstanding treatment for diabetes, has been shown to increase lifespan in both vertebrate and mammalian models. This pleiotropic effect is hypothesized to mimic calorie restriction, a currently proven means of slowing ageing, by decreasing insulin and insulin-like growth factor (IGF)-1 levels and improving insulin sensitivity. However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair. Clinical studies, such as those supported by the UK Clinical Practice Research Datalink service, have reported that diabetes patients treated with metformin live longer than patients without diabetes. Metformin use can also reduce type 2 diabetes mellitus (T2DM) incidence among those at risk, lower cancer incidence, and improve cognitive function, cardiovascular disease (CVD) risk factors and atherosclerosis.ConclusionVarious studies have found that metformin can target several nutrient-sensing, anti-ageing and immune pathways, leading to reductions in oxidative stress, inflammation and DNA damage as well as providing effects similar to those of calorie restriction. However, further trials are still needed to confirm these findings.     

小儿支气管哮喘中药新药临床试验设计与评价技术指南

《儿科常见疾病中药新药临床试验设计与评价技术指南》是中华中医药学会儿科分会临床评价学组制定的、指导儿科中药Ⅱ期、Ⅲ期临床试验和上市后有效性再评价方案设计的、具有病种特色的系列临床评价技术指南, 旨在推动儿科中药临床试验设计与评价水平的提高, 并为临床提供安全有效的儿童用药。采用世界卫生组织(WHO)推荐的“共识会议法”和美国国立卫生研究院(NIH)发展共识方案(GPP)有关原则, 国内全部18个国家药物临床试验机构中医儿科专业的临床儿科专家以及国内相关临床评价专家参加了急性上呼吸道感染、急性支气管炎、支气管哮喘、反复呼吸道感染、厌食、轮状病毒性肠炎、注意缺陷-多动障碍、抽动障碍、遗尿症、手足口病、湿疹11个儿科常见病种指南的起草或多次提出修改建议, 历经3年反复完善, 最终形成共识, 并由中华中医药学会儿科分会于2013年10月发布。本指南从研究背景、研究目标、总体设计、诊断标准、受试者的选择、给药方案、安全性评价、有效性评价、试验流程、数据管理与统计分析、质量保证、相关伦理学要求、试验结束后的医疗措施、资料保存等方面阐述了小儿支气管哮喘中药新药临床试验的设计与评价技术要点, 期望能为申办者与研究者在临床试验方案设计中提供指导。     

抗高尿酸血症药物研究进展

痛风是一种代谢性疾病,危害严重,近年来患病率呈上升趋势。尿酸排泄减少或生成增多所致的高尿酸血症是痛风的主要病因,而高尿酸又与多种疾病密切相关。降低血尿酸水平是治疗痛风,预防痛风复发的重要措施。目前,抗高尿酸血症药物主要有3类,分别是黄嘌呤氧化酶抑制剂、尿酸盐阴离子转运蛋白1(URAT1)抑制剂和尿酸氧化酶类似物。对现有抗高尿酸血症药物的现状以及研究进展进行总结,希望对其研发提供参考。     

黑色素瘤治疗药物的研究进展

黑色素瘤是临床上常见的皮肤恶性肿瘤,且发病率呈逐年增加的趋势。该病恶性程度高,易发生转移。全球新批准并上市的治疗黑色素瘤的治疗药物有威罗菲尼、达拉菲尼、曲美替尼、易普利姆玛、nivolumab以及pembrolizumab,处于研发后期的黑色素瘤治疗药物有cobimetinib、binimetinib、talimogene laherparepvec、贝伐单抗、seviprotimut-L、NGc GM3/VSSP以及c-Kit抑制剂甲磺酸伊马替尼等。对近年来上市和处于研发后期的黑色素瘤的治疗药物进行了详细介绍,同时对其未来发展方向进行了展望,以期为黑色素瘤治疗药物的研发指明方向,给黑色素瘤患者带来希望。