Biology subjects

Cao, P.

Publications and source records attributed to Cao, P..

3 recordsLinked to original sources

bioRxiv2018

Predicting the Outcomes of New Short-Course Regimens for Multi-Drug Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modelling

Short-course regimens for multi-drug resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug, bedaquiline (BDQ), may have the potential to shorten MDR-TB treatment to less than six months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modelling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modelling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (four months) while still maintaining a very high treatment success rate (100% for daily BDQ for two weeks, or 95% for daily BDQ for one week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes then we anticipate clear cost-savings and a subsequent improvement in the efficiency of national TB programs.

systems biology↗

bioRxiv2018

Investigating the efficacy of triple artemisinin-based combination therapies (TACTs) for treating Plasmodium falciparum malaria patients using mathematical modelling

The first line treatment for uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT), which consists of an artemisinin derivative co-administered with a longer acting partner drug. However, the spread of Plasmodium falciparum resistant to both artemisinin and its partner drugs poses a major global threat to malaria control activities. Novel strategies are needed to retard and reverse the spread of these resistant parasites. One such strategy is triple artemisinin-based combination therapy (TACT). We developed a mechanistic within-host mathematical model to investigate the efficacy of a TACT (dihydroartemisinin-piperaquine-mefloquine - DHA-PQ-MQ), for use in South-East Asia, where DHA and PQ resistance are now increasingly prevalent. Comprehensive model simulations were used to explore the degree to which the underlying resistance influences the parasitological outcomes. The effect of MQ dosing on the efficacy of TACT was quantified at varying degrees of DHA and PQ resistance. To incorporate interactions between drugs, a novel model is presented for the combined effect of DHA-PQ-MQ, which illustrates how the interactions can influence treatment efficacy. When combined with a standard regimen of DHA and PQ, the administration of three 8.3 mg/kg doses of MQ was sufficient to achieve parasitological efficacy greater than that currently recommended by WHO guidelines.

pharmacology and toxicology↗

bioRxiv2017

WSL5, a pentatricopeptide repeat protein, is essential for chloroplast biogenesis in rice under cold stress

AbstactChloroplasts play an essential role in plant growth and development, and cold has a great effect on chloroplast development. Although many genes or regulators involved in chloroplast biogenesis and development have been isolated and characterized, identification of novel components associated with cold is still lacking. In this study, we reported the functional characterization of white stripe leaf 5 (wsl5) mutant in rice. The mutant developed white-striped leaves during early leaf development and was albinic when planted under cold stress. Genetic and molecular analysis revealed that WSL5 encodes a novel chloroplast-targeted pentatricopeptide repeat protein. RNA-seq analysis showed that expression of nuclear-encoded photosynthetic genes in the mutant was significantly repressed, and expression of many chloroplast-encoded genes was also significantly changed. Notably, the WSL5 mutation caused defects in editing of rpl2 and atpA, and in splicing of rpl2 and rps12. Chloroplast ribosome biogenesis was impaired under cold stress. We propose that WSL5 is required for normal chloroplast development in rice under cold stress.

genetics↗