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Malaria is an infectious disease caused by Plasmodium group. The mechanisms of antimalarial drugs DHA/CQ are still unclear today. The inhibitory effects (IC50) of single treatments with DHA/CQ or V-ATPase inhibitor Baf-A1 or combination treatments by DHA/CQ combined with Baf-A1 on the growth of Plasmodium falciparum strain 3D7 was investigated. Intracellular cytoplasmic pH and labile iron pool (LIP) were labeled by pH probe BCECF, AM and iron probe calcein, AM, the fluorescence of the probes was measured by FCM. The effects of low doses of DHA (0.2 nM, 0.4 nM, 0.8 nM) on gene expression of V-ATPases (vapE, vapA, vapG) located in the membrane of DV were tested by RT-qPCR. DHA combined with Baf-A1 showed a synergism effect (CI = 0.524) on the parasite growth in the concentration of IC50. Intracellular pH and irons were effected significantly by different doses of DHA/Baf-A1. Intracellular pH was decreased by CQ combined with Baf-A1 in the concentration of IC50. Intracellular LIP was increased by DHA combined with Baf-A1 in the concentration of 20 IC50. The expression of gene vapA was down-regulated by all low doses of DHA (0.2/0.4/0.8 nM) significantly (p < 0.001) and the expression of vapG/vapE were up-regulated by 0.8 nM DHA significantly (p < 0.001). Interacting with ferrous irons, affecting the DV membrane proton pumping and acidic pH or cytoplasmic irons homeostasis may be the antimalarial mechanism of DHA while CQ showed an effect on cytoplasmic pH of parasite in vitro. Lastly, this article provides us preliminary results and a new idea for antimalarial drugs combination and new potential antimalarial combination therapies.

Background Malaria is a fatal disease that presents clinically as a continuum of symptoms and severity, which are determined by complex host-parasite interactions. Clearance of infection is believed to be accomplished by the spleen and mononuclear phagocytic system (MPS), independent of artemisinin treatment. The spleen filters infected red blood cells (RBCs) from circulation through immune-mediated recognition of the infected RBCs followed by phagocytosis. This study evaluated the tolerance of four different strains of mice to Plasmodium berghei strain K173 (P. berghei K173), and the differences in the role of the spleen in controlling P. berghei K173 infection. Methods Using different strains of mice (C57BL/6, BALB/C, ICR, and KM mice) infected with P. berghei K173, the mechanisms leading to splenomegaly, histopathology, splenocyte activation and proliferation, and their relationship to the control of parasitaemia and host mortality were examined and evaluated. Results Survival time of mice infected with P. berghei K173 varied, although the infection was uniformly lethal. Mice of the C57BL/6 strain were the most resistant, while mice of the strain ICR were the most susceptible. BALB/c and KM mice were intermediate. In the course of P. berghei K173 infection, all infected mice experienced significant splenomegaly. Parasites were observed in the red pulp at 3 days post infection (dpi) in all animals. All spleens retained late trophozoite stages as well as a fraction of earlier ring-stage parasites. The percentages of macrophages in infected C57BL/6 and KM mice were higher than uninfected mice on 8 dpi. Spleens of infected ICR and KM mice exhibited structural disorganization and remodelling. Furthermore, parasitaemia was significantly higher in KM versus C57BL/6 mice at 8 dpi. The percentages of macrophages in ICR infected mice were lower than uninfected mice, and the parasitaemia was higher than other strains. Conclusions The results presented here demonstrate the rate of splenic mechanical filtration and that splenic macrophages are the predominant roles in controlling an individual’s total parasite burden. This can influence the pathogenesis of malaria. Finally, different genetic backgrounds of mice have different splenic mechanisms for controlling malaria infection.

Background The combination of anti-glomerular basement membrane (GBM) disease and immunoglobulin A nephropathy (IgAN) has been well documented in sporadic cases, lacking overall assessment in large collections. Herein, we investigated the clinical and immunological characteristics and outcome of this entity. Methods 75 consecutive patients with biopsy-proven anti-GBM disease from March 2012 to March 2020 were screened. Among them, patients with concurrent IgAN were identified and enrolled. The control group included biopsied classical anti-GBM patients during the same period, excluding patients with IgAN, other glomerular diseases or tumors, or patients with unavailable blood samples and missing data. Serum IgG and IgA autoantibodies against GBM were detected by enzyme-linked immunosorbent assay, as were circulating IgG subclasses against GBM. Results 15 patients with combined anti-GBM disease and IgAN were identified, accounting for 20% (15/75) of all patients. Among them, nine were male and six were female, with an average age of 46.7±17.3 years. Thirty patients with classical anti-GBM disease were enrolled as controls, with 10 males and 20 females at an average age of 45.4±15.3 years. Patients with combined anti-GBM disease and IgAN had restricted kidney involvement without pulmonary hemorrhage. Compared with classical patients, anti-GBM patients with IgAN presented with significantly lower levels of serum creatinine on diagnosis (6.2±2.9 v.s. 9.5±5.4mg/dl, P = 0.03) and less occurrence of oliguria/anuria (20%, 3/15 v.s. 57%, 17/30, P = 0.02), but more urine protein excretion [2.37(1.48,5.63) v.s. 1.11(0.63,3.90) g/24h, P = 0.01]. They showed better kidney outcome during follow-up (ESKD: 47%, 7/15 v.s. 80%, 24/30, P = 0.03). The autoantigen and epitope spectrum were comparable between the two groups, but the prevalence of circulating anti-α3(IV)NC1 IgG1(67% v.s. 97%, P = 0.01) and IgG3(67% v.s. 97%, P = 0.01) were lower in patients with IgAN. Conclusions Concurrent IgAN was not rare in anti-GBM disease. Patients showed milder kidney lesions and better recovery after immunosuppressive therapies. It might be partly explained by lower prevalence of anti-GBM IgG1 and IgG3 in these patients.