Curcumin: A Novel Way to Improve Quality of Life for Colorectal Cancer Patients?

Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women. Treatment of metastatic CRC consists of highly toxic chemotherapeutic drug combinations that often negatively affect patient quality of life (QoL). Moreover, chemotherapy-induced toxicity and chemotherapy resistance are among the most important factors limiting cancer treatment and can lead to the interruption or discontinuation of potentially effective therapy. Several preclinical studies have demonstrated that curcumin acts through multiple cellular pathways and possesses both anti-cancer properties against CRC and the capacity to mitigate chemotherapy-related side effects and overcome drug resistance. In this review article, we suggest that the addition of curcumin to the standard chemotherapeutic treatment for metastatic CRC could reduce associated side-effects and overcome chemotherapy resistance, thereby improving patient QoL.     

Does Intrauterine Injection of hCG Improve IVF Outcome? A Systematic Review and a Meta-Analysis

Various interventions have been proposed to improve embryo implantation in IVF. Among these, intrauterine injections of human chorionic gonadotropin seem to have promising results. Consequently, we conducted a review and meta-analysis to assess IVF outcomes by comparing couples who underwent intrauterine hCG injection transfer versus those who underwent embryo transfer with intrauterine injection of placebo, or without any additional intervention. The primary outcome was the clinical pregnancy rate. Secondary outcomes were the implantation rate, miscarriage rate, and live birth rate. A meta-analysis was conducted using the random effects model, while bias within studies was detected using the Cochrane risk of bias tool. Ectopic pregnancies and stillbirths were also assessed. The clinical pregnancy (RR 1.38, 95% CI 1.17–1.62, p < 0.0001) and implantation rate (RR 1.40, 95% CI 1.12–1.75, p = 0.003) were significantly higher in women who underwent hCG injection than in the control group. These significant effects persisted only in women who underwent cleavage-stage embryo transfer. No significant differences between groups were observed in the other secondary outcomes. In conclusion, our systematic review and meta-analysis demonstrate that intrauterine injection of hCG could be a valuable approach in women who undergo cleavage-stage embryo transfer. Given the lack of data about the live birth rate, caution should be exercised in interpreting these data.     

Does Short-Term Dietary Omega-3 Fatty Acid Supplementation Influence Brain Hippocampus Gene Expression of Zinc Transporter-3?

Dietary omega-3 fatty acids have been recognized to improve brain cognitive function. Deficiency leads to dysfunctional zinc metabolism associated with learning and memory impairment. The objective of this study is to explore the effect of short-term dietary omega-3 fatty acids on hippocampus gene expression at the molecular level in relation to spatial recognition memory in mice. A total of 24 male BALB/c mice were randomly divided into four groups and fed a standard pellet as a control group (CTL, n = 6), standard pellet added with 10% (w/w) fish oil (FO, n = 6), 10% (w/w) soybean oil (SO, n = 6) and 10% (w/w) butter (BT, n = 6). After 3 weeks on the treatment diets, spatial-recognition memory was tested on a Y-maze. The hippocampus gene expression was determined using a real-time PCR. The results showed that 3 weeks of dietary omega-3 fatty acid supplementation improved cognitive performance along with the up-regulation of α-synuclein, calmodulin and transthyretin genes expression. In addition, dietary omega-3 fatty acid deficiency increased the level of ZnT3 gene and subsequently reduced cognitive performance in mice. These results indicate that the increased the ZnT3 levels caused by the deficiency of omega-3 fatty acids produced an abnormal zinc metabolism that in turn impaired the brain cognitive performance in mice.     

A Decade of the Human Genome Sequence—How Does the Medicinal Chemist Benefit?

Many have claimed that the sequencing of the human genome has failed to deliver the promised new era of drug discovery and development. Here, we argue that in fact, the availability of the human genome sequence and the genomics technologies that resulted from those research efforts have had a major impact on drug discovery. Medicinal chemists are actively using the data gleaned from structural genomics projects over the past decade to design more selective and more effective drug candidates. For example, large superfamilies of related enzymes, such as the kinome, proteome, proteasome, transportome, identified because of the sequencing of the human genome represent a huge number of potential drug targets. Ten years on, we're able to design multitarget drugs where the selectivity for a certain subgroup of receptors can lead to increased efficacy rather than the side effects traditionally associated with "off-targets". New trends and discoveries in biomedical research are notoriously slow to show their value, and this is also true for genomics technologies. However, the examples we've selected show that these are firmly set in the drug-discovery process, and without the human genome sequence, a number of current clinical candidates and promising drug leads would not have been possible.     

Why Does the Novel Coronavirus Spike Protein Interact so Strongly with the Human ACE2? A Thermodynamic Answer

The SARS-CoV-2 pandemic is the biggest health concern today, but until now there is no treatment. One possible drug target is the receptor binding domain (RBD) of the coronavirus’ spike protein, which recognizes the human angiotensin-converting enzyme 2 (hACE2). Our in silico study discusses crucial structural and thermodynamic aspects of the interactions involving RBDs from the SARS-CoV and SARS-CoV-2 with the hACE2. Molecular docking and molecular dynamics simulations explain why the chemical affinity of the new SARS-CoV-2 for hACE2 is much higher than in the case of SARS-CoV, revealing an intricate pattern of hydrogen bonds and hydrophobic interactions and estimating a free energy of binding, which is consistently much more negative in the case of SARS-CoV-2. This work presents a chemical reason for the difficulty in treating the SARS-CoV-2 virus with drugs targeting its spike protein and helps to explain its infectiousness.     

水系锌离子电池Al3 预嵌(NH4)2V10O25?8H2O正极材料的制备及其电化学性能Q

NH4VO3为钒源、C2H2O4?2H2O为还原剂,采用水热法合成了(NH4)2V10O25?8H2O(NVO)纯相,以Al(NO3)3?9H2O为铝源对材料进行层间Al3 预嵌进行改性(Al-NVO),通过XRD、SEM、TEM以及EDS对材料的物相和形貌进行表征。结果表明,Al3 均匀分散于材料中,Al3 预嵌使材料形貌由密集堆叠的片状结构向更细小更分散的纳米片状结构转变。恒流充放电,循环伏安(CV)及恒电流间歇式滴定技术(GITT)等电化学性能测试表明,Al3 预嵌能有效提高材料的容量,倍率性能及循环稳定性能。样品Al-NVO材料在0.5A/g的电流密度下首次放电比容量为329 mAh/g,经过100次循环,比容量为252mAh/g。在2.0A/g电流密度下,经过1200次循环容量仍有122.8 mAh/g,容量保持率高达 94.6%。通过不同扫速下的循环伏安及赝电容计算,层间预嵌Al3 有效提高了Zn2 的扩散动力学,改善了材料的电化学性能。