There are no effective therapies for patients with Coronavirus disease-2019 (COVID-19). Forty-one patients with confirmed COVID-19 were enrolled in the study and divided into two groups: artemisinin-piperaquine (AP) group (n=23) and control group (n=18). The primary outcome was the time taken to reach undetectable levels of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and the percentage of participants with undetectable SARS-CoV-2 on day 7, 10, 14, and 28. The computed tomography (CT) imaging changes within ten days, the corrected QT interval changes, adverse events, and abnormal laboratory parameters were the secondary outcomes. The mean time to reach undetectable viral RNA (mean± standard deviation) was 10.6±1.1 days (95% confidence interval [CI]: 8.4-12.8) for AP group and 19.3±2.1 days (95% CI: 15.1-23.5) for the control group. The percentage of patients with undetectable viral RNA on day 7, 10, 14, 21, and 28 were 26.1%, 43.5%, 78.3%, 100%, and 100%, respectively, in the AP group and 5.6%, 16.7%, 44.4%, 55.6% and 72.2%, respectively, in the control group. The CT imaging within ten days post-treatment showed no significant differences between the two groups (p>0.05). Both groups had mild adverse events. In patients with mild to moderate COVID-19, the time to reach undetectable SARS-CoV-2 was significantly shorter in the AP group than that in the control group. However, physicians should consider the QT interval changes before using AP.

As a folk medicine, Moringa oleifera L. is used effectively to treat inflammatory conditions and skin diseases. However, its mechanism of action is not well understood, limiting its medical use. We isolated and identified three compounds, namely niazirin, marumoside A and sitosterol-3-O-β-d-glucoside, from the seeds of Moringa oleifera, and studied their effects on the expression of Th17-relevant cytokines (IL-12/IL-23 p40, IL-17A, IL-22 and IL-23 p19) using lipopolysaccharide-stimulated THP-1 cells. Additionally, as Th17 plays a critical role in the pathogenesis of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis-like skin lesion mouse model to study their potential therapeutic application in vivo. The compounds suppressed the expression of IL-12/IL-23 p40, IL-17A, IL-22 and IL-23 p19 in vitro, and in vivo they ameliorated psoriasis-like skin lesions, decreased IL-17A mRNA expression, and increased the expression of keratinocyte differentiation markers. To our knowledge, this is the first report regarding the mechanism and therapeutic application of Moringa oleifera seeds to treat psoriasis-like lesions in vivo.

Background: Malaria is a parasitic infection transmitted by mosquito vectors, commonly found in tropical regions, and characterized by high morbidity and mortality. It causes a heavy disease burden in Sao Tome and Principe (STP), an island country in West Africa which at one time had a high incidence of malaria. Objective: This study aims to analyze the trend of disease burden of malaria in STP. Methods: The crude and age-standardized incidence, mortality, and disability-adjusted life years (DALYs) rate data of malaria were extracted from GBD 2019. Joinpoint 4.9 software was used to calculate the annual percentage change (APC) and the average annual percentage change (AAPC), which were also used to indicate the change in disease burden by different stages. Results: In general, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) of malaria presented a decreasing trend between 1990 and 2019, with an average annual decrease of 5.6%, 6.2%, and 10.7%, respectively, in STP. Specifically, all indicators first presented an increasing trend from 1990 to about 2000, followed by a decreasing trend until 2019, although the incidence rebounded slightly after 2015. Overall, the ASIR, ASMR, and ASDR of malaria reduced by 77.08%, 87.84%, and 82.21%, respectively, in 2019 as compared to 1990. No significant differences in disease burden were found between males and females between 2005 and 2019. Children who were under 5 years old showed a relatively small decrease in the rate of DALYs as compared to other age groups, but remained the group with the highest disease burden of malaria in the country. Conclusions: The disease burden of malaria in STP showed a significant decrease between 1990 and 2019, but it will still be challenging to achieve the goal of eliminating malaria by 2025. The government and relevant authorities should aim to strengthen the prevention and surveillance of malaria and tailor population-specific interventions in order to reduce the disease burden of malaria in STP.

Background: H1N1 is one of the major subtypes of influenza A virus (IAV) that causes seasonal influenza, posing a serious threat to human health. A traditional Chinese medicine combination called Qingxing granules (QX) is utilized clinically to treat epidemic influenza. However, its chemical components are complex, and the potential pharmacological mechanisms are still unknown. Methods: QX’s effective components were gathered from the TCMSP database based on two criteria: drug-likeness (DL ≥ 0.18) and oral bioavailability (OB ≥ 30%). SwissADME was used to predict potential targets of effective components, and Cytoscape was used to create a “Herb-Component-Target” network for QX. In addition, targets associated with H1N1 were gathered from the databases GeneCards, OMIM, and GEO. Targets associated with autophagy were retrieved from the KEGG, HAMdb, and HADb databases. Intersection targets for QX, H1N1 influenza, and autophagy were identified using Venn diagrams. Afterward, key targets were screened using Cytoscape’s protein–protein interaction networks built using the database STRING. Biological functions and signaling pathways of overlapping targets were observed through GO analysis and KEGG enrichment analysis. The main chemical components of QX were determined by high-performance liquid chromatography (HPLC), followed by molecular docking. Finally, the mechanism of QX in treating H1N1 was validated through animal experiments. Results: A total of 786 potential targets and 91 effective components of QX were identified. There were 5420 targets related to H1N1 and 821 autophagy-related targets. The intersection of all targets of QX, H1N1, and autophagy yielded 75 intersecting targets. Ultimately, 10 core targets were selected: BCL2, CASP3, NFKB1, MTOR, JUN, TNF, HSP90AA1, EGFR, HIF1A, and MAPK3. Identification of the main chemical components of QX by HPLC resulted in the separation of seven marker ingredients within 195 min, which are amygdalin, puerarin, baicalin, phillyrin, wogonoside, baicalein, and wogonin. Molecular docking results showed that BCL2, CASP3, NFKB1, and MTOR could bind well with the compounds. In animal studies, QX reduced the degenerative alterations in the lung tissue of H1N1-infected mice by upregulating the expression of p-mTOR/mTOR and p62 and downregulating the expression of LC3, which inhibited autophagy. Conclusions: According to this study’s network pharmacology analysis and experimental confirmation, QX may be able to treat H1N1 infection by regulating autophagy, lowering the expression of LC3, and increasing the expression of p62 and p-mTOR/mTOR.

Vanillic acid, a phenolic compound mainly obtained from the foot of Picrorhiza scrophulariiflora Pennell, has been demonstrated to possess a cardiovascular-protective effect in previous studies. However, there is lack of research on vanillic acid protecting cardiomyocytes from oxidative stress injury by mediating mitophagy. In the present study, oxidative stress injury in the H9c2 cell line was induced by H₂O₂. Our results confirmed that vanillic acid mitigated apoptosis and injury triggered by oxidative stress, evidenced by the decline in production of reactive oxygen species and malondialdehyde and level of lactate dehydrogenase and the increase of superoxide dismutase and glutathione. The use of vanillic acid could also improve the polarization of mitochondrial membrane potential and decrease the cellular calcium level. After treatment by vanillic acid, impaired autophagy flux and mitophagy were improved, and the length of mitochondria was restored. Vanillic acid increased the expression of PINK1, Parkin, Mfn2, and the ratio of LC3-II/LC3-I and decreased the expression of p62. But, under the intervention of mitophagy inhibitor 3-MA, vanillic acid could not change the expression of PINK1/Parkin/Mfn2 and downstream genes to affect cell autophagy, mitophagy, and mitochondrial function. Our findings suggested that vanillic acid activated mitophagy to improve mitochondrial function, in which the PINK1/Parkin/Mfn2 pathway could be the potential regulatory mechanism.

Garcinia biflavonoid 1 (GB1) is one of the active chemical components of Garcinia kola and is reported to be capable of reducing the intracellular lipid deposition, which is the most significant characteristic of non-alcoholic fatty liver disease. However, its bioactive mechanism remains elusive. In the current study, the lipid deposition was induced in HepG2 cells by exposure to oleic acid and palmitic acid (OA&PA), then the effect of GB1 on lipid metabolism and oxidative stress and the role of regulating PPARα in these cells was investigated. We found that GB1 could ameliorate the lipid deposition by reducing triglycerides (TGs) and upregulate the expression of PPARα and SIRT6, suppressing the cell apoptosis by reducing the oxidative stress and the inflammatory factors of ROS, IL10, and TNFα. The mechanism study showed that GB1 had bioactivity in a PPARα-dependent manner based on its failing to improve the lipid deposition and oxidative stress in PPARα-deficient cells. The result revealed that GB1 had significant bioactivity on improving the lipid metabolism, and its potential primary action mechanism suggested that GB1 could be a potential candidate for management of non-alcoholic fatty liver disease.