METHODS: An agent-based model (ABM) is a relatively new approach that provides a framework for analyzing the heterogeneity of the interactions, along with biological and environmental factors in such complex systems. The objective of this research is to design and develop an ABM that uses Geospatial Information System (GIS) capabilities, biological behaviors of vectors and reservoir hosts, and an improved Susceptible-Exposed-Infected-Recovered (SEIR) epidemic model to explore the spread of ZCL. Various scenarios were implemented to analyze the future ZCL spreads in different parts of Maraveh Tappeh County, in the northeast region of Golestan Province in northeastern Iran, with alternative socio-ecological conditions.
RESULTS: The results confirmed that the spread of the disease arises principally in the desert, low altitude areas, and riverside population centers. The outcomes also showed that the restricting movement of humans reduces the severity of the transmission. Moreover, the spread of ZCL has a particular temporal pattern, since the most prevalent cases occurred in the fall. The evaluation test also showed the similarity between the results and the reported spatiotemporal trends.
CONCLUSIONS: This study demonstrates the capability and efficiency of ABM to model and predict the spread of ZCL. The results of the presented approach can be considered as a guide for public health management and controlling the vector population .
METHODS: Gerbils, 5-7 weeks old were infected by PbA via intraperitoneal injection of 1 × 106 (0.2 mL) infected red blood cells. Parasitemia, weight gain/loss, hemoglobin concentration, red blood cell count and body temperature changes in both control and infected groups were monitored over a duration of 13 days. RNA was extracted from the brain, spleen and whole blood to assess the immune response to PbA infection. Organs including the brain, spleen, heart, liver, kidneys and lungs were removed aseptically for histopathology.
RESULTS: Gerbils were susceptible to PbA infection, showing significant decreases in the hemoglobin concentration, RBC counts, body weights and body temperature, over the course of the infection. There were no neurological signs observed. Both pro-inflammatory (IFNγ and TNF) and anti-inflammatory (IL-10) cytokines were significantly elevated. Splenomegaly and hepatomegaly were also observed. PbA parasitized RBCs were observed in the organs, using routine light microscopy and in situ hybridization.
CONCLUSION: Gerbils may serve as a good model for severe malaria to further understand its pathogenesis.
RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter. Differentiated clusters of beta-like cells co-expressed insulin with the transcription factors Pdx1, Nkx2.2, Nkx6.1, and MafA, and secreted significant levels of insulin in response to glucose challenges. In vivo, undifferentiated MDSC injected into streptozotocin (STZ)-treated mice engrafted within 48 h specifically to damaged pancreatic islets and were shown to differentiate and express insulin 10-12 days after injection. In addition, injection of MDSC into hyperglycemic diabetic mice reduced their blood glucose levels for 2-4 weeks.
CONCLUSION: These data show that MDSC are capable of differentiating into mature pancreatic beta islet-like cells, not only upon culture in vitro, but also in vivo after systemic injection in STZ-induced diabetic mouse models. Being nonteratogenic, MDSC can be used directly by systemic injection, and this potential reveals a promising alternative avenue in stem cell-based treatment of beta-cell deficiencies.