Lipid carriers for mRNA delivery

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

Improving cancer immunotherapy via co-delivering checkpoint blockade and thrombospondin-1 downregulator

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

The prevalence of Candida albicans and its relationship with early childhood caries among children of Uygur and Han nationalities in Kashi city / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the prevalence of Candida albicans and early childhood caries(ECC) among 3-5 years old children of Uygur and Han nationalities in Kashi city, Xinjiang province.</p><p><b>METHODS</b>Totally 397 generally healthy children(Uyghurs 256, Hans141) aged 3-5 years were recruited randomly in Kashi city using the stratified cluster random method. Dental plaque samples were collected from carious tooth tissues of children with ECC and from supragingival tooth sites of caries free(CF) children, respectively. Plaque samples were cultured and Candida albicans were isolated selectively by using CHROM agar candida medium. The isolates were further identified using methods of germ tubes test, Gram stain and PCR molecular biology. The data were analyzed using Pearson χ(2) test and Spearman analysis.</p><p><b>RESULTS</b>The prevalenses of Candida albicans were 44.5% (114/256) in Han children and 31.2%(44/141) in Urgur children, respectively(P=0.009). Candida albicans could be isolated from 48.8% (124/254) of ECC children, while 23.8% (34/143) of CF ones(P=0.000). The frequencies of Candida albicans acquisition of boys and girls of Uygur children were 51.2%(66/129) and 37.8%(48/127), respectively (P=0.031). The frequencies of Candida albicans acquisition increased with the decayed missing filled tooth (dmft) scores. For both Uygur and Hanchildren, the detection rates of Candida albicans were correlated with dmft scores(Uygur r=0.350, P=0.001; Han r=0.276, P=0.000).</p><p><b>CONCLUSIONS</b>The oral Candida albicans distributions were different in Uygur and Han ethnic groups. There were significant correlations between the presence of Candida albicans and ECC severityas well as score of dmft. There was a difference of the Candida albicans distributions between boys and girls among Uygur children. Candida albicans might be one of the important cariogenic microorganisms in ECC.</p>

A comparative study on determination of blood drug concentration of sodium valproate in epileptic children between EMIT and HPLC / 中国生化药物杂志

Objective To study the correlation of blood drug concentration determination of sodium valproate in children with epilepsy by using enzyme-multiplied immunoassay test (EMIT) and high performance liquid chromatography (HPLC), so as to provide basis of selection in clinical determination of sodium valproate ( VPA) .Methods 200 blood samples of epileptic children taking sodium valproate were collected, blood concentration were determined by EMIT and HPLC method, and the correlation was analyzed.Results The following regression equation was obtained by determination results of HPLC (X) and EMIT (Y): Y=1063.517X-331.351(r=0.933), which had significant correlation (P<0.05).The plasma concentration of VPA determined by EMIT was higher than that by HPLC.Conclusion The determination results of VPA concentration in epileptic children by using EMIT and HPLC has significant correlation, and it should choose the suitable method to determine the blood drug concentration of VPA based on the actual situation.

Cost-Effectiveness Analysis of4Therapeutic Schemes in the Treatment of Type 2 Diabetes / 中国药房

OBJECTIVE:To discuss the cost-effectiveness of4therapeutic schemes in the treatment of Type2diabetes.METHODS:Cost-effectiveness analyses were made on4therapeutic schemes by using pharmacoeconomical principle,which were:metformin+clipizde(Scheme A),metformin+pioglitazone(Scheme B),metformin+repaglinide(Scheme C),and met-formin+novolin30R(Scheme D).RESULTS:There was no significant difference in the total effective rate among4schemes.The cost-effectiveness ratios in Scheme A,B,C and D were2.21,3.21,2.63,and6.54,respectively.The cost-effectiveness ratios increments in Scheme B,C,and D were64.82,—6.41,and51.25as against Scheme A.CONCLUSION:Among the4schemes,Scheme A is the preferable choice.