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.

Lipid accumulation, oxidative stress, and inflammation in hepatocytes are features of nonalcoholic fatty liver disease (NAFLD). Garcinia biflavonoid 1a (GB1a) is a natural product capable of hepatic protection. In this study, the effect of GB1a on anti-inflammatory, antioxidant, and regulation of the accumulation in HepG2 cells and mouse primary hepatocytes (MPHs) was investigated, and its regulatory mechanism was further explored. The result showed that GB1a reduced triglyceride (TG) content and lipid accumulation by regulating the expression of SREBP-1c and PPARα; GB1a reduced reactive oxygen species (ROS) and improved cellular oxidative stress to protect mitochondrial morphology by regulating genes Nrf2, HO-1, NQO1, and Keap1; and GB1a reduced the damage of hepatocytes by inhibiting the expression of inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65. The activities of GB1a were lost in liver SIRT6-specific knockout mouse primary hepatocytes (SIRT6-LKO MPHs). This indicated that activating SIRT6 was critical for GB1a to perform its activity, and GB1a acted as an agonist of SIRT6. It was speculated that GB1a may be a potential drug for NAFLD treatment.

Introduction: The incidence of diabetes is rising annually, significantly impacting public health and imposing a substantial economic burden on society. Ophiopogonin D (Op D) exhibits certain hypoglycemic effects; however, its mechanisms remain unclear.Methods: β-cell dedifferentiation, distinct from β-cell apoptosis, is a pathogenic mechanism we aim to explore regarding Op D’s regulatory effects. We established an animal model of β-cell dedifferentiation to assess Op D’s impact on glucose tolerance, blood glucose levels, and insulin secretion. We employed immunohistochemistry and immunofluorescence to analyze the expression levels of dedifferentiation-related proteins. Additionally, we created an in vitro β-cell dedifferentiation model using INS-1 cells to evaluate Op D’s influence on insulin secretion and dedifferentiation. Transcriptomic analysis was conducted to explore potential mechanisms by which Op D ameliorates dedifferentiation, with further validation via Western blotting and immunofluorescence. Flow cytometry, fluorescence microscopy, and related assays were used to assess Op D’s effects on oxidative stress. Endoplasmic reticulum (ER) tracing agents marked the ER, and laser confocal microscopy examined ER morphology, with ER stress inducers and inhibitors employed to clarify Op D’s mechanisms.Results: Results indicated that Op D reduced blood glucose levels, improved glucose tolerance, enhanced insulin secretion, mitigated pancreatic atrophy, and increased PDX1 and FOXO1 expression levels. Furthermore, Op D inhibited ER stress, decreased GRP78 expression, reduced NGN3 levels, elevated PDX1, NKX6.1, and MAFA expression, and decreased oxidative stress-related products (ROS, MDA) while increasing SOD and GSH levels.Discussion: These findings demonstrate that Op D can improve β-cell dedifferentiation by modulating the GRP78/ROS/PDX1 pathway to inhibit ER stress.

The WHO recommends artemisinin-based combination regimens for uncomplicated Plasmodium falciparum malaria. One such combination is artemisinin-piperaquine tablets (ATQ). ATQ has outstanding advantages in anti-malarial, such as good efficacy, fewer side effects, easy promotion and application in deprived regions. However, the data about the reproductive and endocrine toxicity of ATQ remains insufficient. Thus, we assessed the potential effects of ATQ and its individual components artemisinin (ART) and piperaquine (PQ) on the reproductive and endocrine systems in Wistar rats. The unfertilized female rats were intragastric administrated with ATQ (20, 40, and 80 mg/kg), PQ (15, 30, and 60 mg/kg), ART (2.5, 5, and 10 mg/kg), or water (control) for 14 days, respectively. The estrous cycle and serum levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), prostaglandin (PG), and adrenocorticotropic hormone (ACTH) were determined. The weights of the kidney, adrenal gland, uterus, and ovaries were measured. The histopathological examinations of the adrenal gland, ovary, uterus, and mammary gland were performed. Compared with the control group, there were no significant differences in the examined items of female rats in the ART groups, including general observation, estrous cycle, hormonal level, organ weight, and histopathological examination. The estrous cycle of female rats was disrupted within 4–7 days after ATQ or PQ administration, and then in a persistent dioestrus phase. At the end of administration, ATQ and PQ at three doses induced decreased PG, increased ACTH, increased adrenal weight and size, and pathological lesions in the adrenal gland and ovary, including vasodilation and hyperemia in the adrenal cortex and medulla as well as hyperplasia and vacuolar degeneration, ovarian corpus luteum surface hyperemia, numerous but small corpus luteum, and disordered follicle development. But the serum levels of E2, FSH, LH, and PRL did not change obviously. These adverse effects in ATQ or PQ treated rats could not completely disappear after 21 days of recovery. Based on the results of this study, ART had no obvious reproductive and endocrine effects on female rats, while ATQ and PQ caused adrenal hyperplasia, increased ACTH, decreased PG, blocked estrus, corpus luteum surface hyperemia, and disrupted follicle development in female rats. These events suggest that ATQ and PQ may interfere with the female reproductive and endocrine systems, potentially reducing fertility.

Background: Recent setbacks in malaria control in Comoros demand a reassessment of its evolving epidemiology. Methods: Using the Global Burden of Disease (GBD) Study 2021 data, we analyzed malaria trends from 2010 to 2021, stratified by sex. We quantified the contributions of demographic and epidemiological factors to these trends and identified risk factors for malaria-related disability-adjusted life years (DALYs). Results: From 2010 to 2021, malaria cases, deaths, and DALYs in Comoros fell by −90.22%, −94.44%, and −94.88%; and the corresponding age-standardized rates declined with EAPCs of −18.70% (95% CI: −33.77 to −0.20), −23.89% (95% CI: −36.58 to −8.66), and −24.49% (95% CI: −36.88 to −9.66), with steeper declines in males. Nevertheless, all indicators increased in 2018 and again in 2021. In sub-Saharan Africa, only cases increased, while other metrics declined slightly. In Comoros, incidence shifted mainly to adults ≥25 years, unlike sub-Saharan Africa, where children < 5 years were most affected. Population growth drove increases in cases, deaths and DALYs, whereas epidemiological shifts had the opposite effect. Child underweight was the leading risk factor for malaria DALYs. Conclusions: Existing interventions can achieve malaria control in Comoros; however, rebounds in 2018 and 2021 highlight the need to identify and address drivers of resurgence.