17 research outputs found
Surfactant Protein D Is Altered in Experimental Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome
No full textSurfactant protein D (SP-D) is in the collectin family of C-type lectins and plays an important role in the regulation of inflammation and the innate immune defense against pathogens. This protein has been proposed as a biomarker for acute lung injury. However, the expression of SP-D in the lung and the circulating levels of SP-D during malaria infection have received limited attention. Therefore, the aim of this study was to determine the location and expression of the SP-D protein in lung tissue and to measure the plasma level of SP-D in experimental malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Malaria-infected mice induced by Plasmodium berghei ANKA were classified into two groups, namely, the ALI/ARDS and non-ALI/ARDS groups, according to lung histopathology. The lungs of uninfected mice were used as a control group. The location and expression of SP-D in the lung tissues were investigated by immunohistochemical staining and Western blot analysis. In addition, the level of SP-D in plasma and lung homogenate was measured by an enzyme-linked immunosorbent assay. Immunohistochemical staining of SP-D was significantly increased in the lung tissues of the malaria-infected mice in the ALI/ARDS group compared with that in the malaria-infected mice in the non-ALI/ARDS group and the mice in the control group (p < 0.05). The levels of SP-D in the plasma and lung homogenate were significantly increased in the malaria-infected mice in the ALI/ARDS group compared with those in the malaria-infected mice in the non-ALI/ARDS group and the mice in the control group (p < 0.05). There was a significant positive correlation between SP-D in the plasma and SP-D in the lung homogenate (rs = 0.900, p = 0.037). In conclusion, this study demonstrated increased expression levels of SP-D in the lung tissue and high levels of plasma SP-D in the malaria-infected mice with ALI/ARDS compared with those in the mice in the other groups. The current study supports that the elevation of the plasma SP-D level may provide useful biological confirmation of the diagnosis of ALI/ARDS during malaria infection
Mean TS for S1PR and SphK expression in liver tissues from the control (n = 10) and PbA-infected (n = 10) groups.
No full textMean TS for S1PR and SphK expression in liver tissues from the control (n = 10) and PbA-infected (n = 10) groups.</p
Fig 1 -
No full textHistopathological changes in liver tissues from control (A) and PbA-infected mice (B). The histomorphological changes in PbA-infected mice include hemozoin deposition (indicated by yellow arrowheads) and apoptotic hepatocytes (indicated by black asterisks) around the central vein. Central vein (CV); Portal tract (PT). All images are shown at 200× magnification. Scale bar = 100 μm.</p
A schematic illustration of SphK/S1PR signaling during malaria infection.
No full textPlasmodium parasite-infected red blood cells induce the accumulation of macrophages, neutrophils, and monocytes, which further initiates the release of proinflammatory cytokines such as TNF-α, IL-1, and IL-6. These proinflammatory cytokines, especially TNF-α, bind to specific receptors on the cell membrane, which can activate sphingomyelin hydrolysis. Next, ceramide can be hydrolyzed to sphingosine by neutral ceramidase. Then, SphKs phosphorylate sphingosine to generate S1P, which directly induces NF-κB activation and translocates to the extracellular space, where it can bind S1PRs and stimulate intracellular downstream signaling, resulting in inflammation and cell survival, proliferation, and migration. In addition, S1P can be degraded into ethanolamine phosphate and hexadecenal; in particular, hexadecenal can stimulate further inflammation in the cytoplasm.</p
Fig 2 -
No full textImmunoperoxidase staining for SphK and S1PR in liver tissues from control (A, C, E, G, I) and PbA-infected mice (B, D, F, H, J). Hepatocytes (H), Kupffer cells (K), sinusoids (S), and central veins (CVs). All images are shown at 200× magnification. Scale bar = 50 μm.</p
Grading system for four main histological features to assess the severity of liver injury.
No full textGrading system for four main histological features to assess the severity of liver injury.</p
Mean scores of four main histological features in tissues from the control (n = 10) and PbA-infected groups (n = 10).
No full textMean scores of four main histological features in tissues from the control (n = 10) and PbA-infected groups (n = 10).</p
Relative SphK and S1PR mRNA expression as measured by real-time PCR.
No full textData are presented as the mean ± SD of triplicate experiments. *p < 0.05 compared with the control group.</p
Exploring Potential Antimalarial Candidate from Medicinal Plants of Kheaw Hom Remedy
No full textThe Kheaw Hom remedy is a traditional Thai medicine widely used to treat fevers. Some plant ingredients in this remedy have been investigated for their antimicrobial, antiviral, anti-inflammatory, and antioxidant activities. However, there have been no reports on the antimalarial activities of the medicinal plants in this remedy. Therefore, this study focuses on identifying potential antimalarial drug candidates from the medicinal plant ingredients of the Kheaw Hom remedy. Eighteen plants from the Kheaw Hom remedy were extracted using distilled water and ethanol. All extracts were investigated for their in vitro antimalarial activity and cytotoxicity. An extract that exhibited good in vitro antimalarial activity and low toxicity was selected for further investigation by using Peter’s 4-day suppressive test and an acute oral toxicity evaluation in mice. Based on the in vitro antimalarial activity and cytotoxicity studies, the ethanolic extract of Globba malaccensis rhizomes showed promising antimalarial activity against the Plasmodium falciparum K1 strain (IC50 = 1.50 µg/mL) with less toxicity to Vero cells (CC50 of >80 µg/mL). This extract exhibited a significant dose-dependent reduction in parasitemia in P. berghei-infected mice. The maximum suppressive effect of this extract (60.53%) was observed at the highest dose administered (600 mg/kg). In a single-dose acute toxicity test, the animals treated at 2000 mg/kg died within 48 h after extract administration. In conclusion, our study indicates that the ethanolic extract of G. malaccensis rhizomes exhibited in vitro and in vivo antimalarial activities, which could serve as a promising starting point for antimalarial drug
