Browsing by Author "Chen, Lu"
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Item Adaptation and carry over effects of extreme sporadic heat stress in Culex mosquitoes(Elsevier, 2024-10-09) Padde, John Roberts; Zhou, Yinghui; Chen, Yunxuan; Zhu, Yuxiao; Yang, Yuxuan; Hou, Min; Chen, Lu; Xu, Zhipeng; Zhang, Donghui; Chen, LinMosquitoes, as temperature-sensitive ectothermic vectors, exhibit temperature-dependence. This study investigates Culex pipiens pallens (Cx. pallens) responses to abrupt temperature increases and their implications on mosquito physiology. First instar larvae (24hr post hatching) and newly enclosed adults (24hr post emergence) were separately exposed to heat shock regimes of 33 °C, 37 °C, and 42 °C for 3 days alongside a control temperature of 27 °C. Results showed that mortality was triggered at 42 °C within a day. Adult male mosquitoes were less tolerant to all temperatures than larvae and adult females (p < 0.05). Exposing larvae to constant temperatures for 3 days significantly decreased larvae's development time, growth rate and adult emergence (p < 0.05). Reproductive fitness was significantly reduced (p < 0.05) in males emerging from larvae exposed to 37 °C. Life table parameters showed significant increased mortality rate, kill power and decreased life expectancy at the embryonic stage (p < 0.05). Furthermore, heatwaves deactivated the Transient receptor protein ankyrin 1 at 37 °C (p < 0.05) in larvae but not adults. Calmodium, Heat shock protein 90, and small heat shock protein expression were significantly decreased in larvae at 37 °C (p < 0.05) as compared to larvae raised at 33 °C and 27 °C. In conclusion, we classified the heat waves into three categories: adaptable (33 °C), critical (37 °C), and fatal (42 °C). Prolonged exposure of Culex pallens larvae to extreme heat affects the male reproductive output. These findings may serve as an important reference for forecasting vector and pest dynamics and used to tailor mosquito prevention and control measures.Item The impact of environmental and host factors on wolbachia density and efficacy as a biological tool(Decoding Infection and Transmission, 2023-11-15) Padde, John Roberts; Lu, Qingyu; Long, Yuang; Zhang, Donghui; Hou, Min; Chen, Lu; Xu, Zhipeng; Chen, Lin; Ji, MinjunWolbachia, a bacterium found naturally in some species of Aedes and Culex mosquitoes, has gained significant attention for it's potential in controlling mosquito-borne diseases and suppressing mosquito populations. However, Wolbachia-mediated pathogen blockage, Wolbachia dynamics in field populations and vertical transmission have been reported to be density-dependent. Several factors, including host genetics, diet, temperature, and co-infections can influence Wolbachia titers within its host. The interplay between these factors can have significant influence on the effectiveness of Wolbachia-mediated pathogen blockage and cytoplasmic incompatibility. However, there is a knowledge gap regarding the regulation of Wolbachia density within its host, which could affect its effectiveness as a biocontrol tool. Therefore, this review aims to understand the complex tripartite association between the environment, host, and endosymbiont, and how these relationships are crucial in harnessing the full potential of Wolbachia as a biological tool. Further, we highlight how host, pathogen, and environmental factors influence Wolbachia density and how their interplay can impact CI and WMPB. We further review the strategies adopted to maintain/control Wolbachia densities in field populations.Item Novel anti-inflammatory peptide alleviates liver ischemia-reperfusion injury(Journal of Biomedical Research, 2024-04-30) Xu, Xuejun; Sun, Kaineng; Chang, Hao; Shen, Chunxiang; Li, Xiangdong; Ni, Yangyue; Zhu, Yuxiao; Wang, Huiquan; Xiong, Ruiyan; Padde, Jon Rob; Xu, Zhipeng; Chen, Lin; Chen, Lu; Hou, Min; Pu, Liyong; Ji, MinjunIschemia-reperfusion injury (IRI) remains inevitable in liver surgeries, macrophages play a critical role in the development of IRI, but little is known about the macrophages regulate pathogenesis of IRI. Based on target guided screening, we identified a small 3 kDa peptide (SjDX5-271) from various schistosome egg-derived peptides that induced M2 macrophage polarization. SjDX5-271 treatment protected the mice against liver IRI through promoting M2 macrophage polarization, the protective effect was abrogated when the macrophages were depleted. Transcriptomic sequencing showed that the TLR signaling pathway was significantly inhibited in macrophages derived from the SjDX5-271 treatment group. We further identified that SjDX5-271 promotes M2 macrophage polarization by inhibiting the TLR4/MyD88/NF-κB signaling pathway and further alleviates hepatic inflammation in liver IRI. Collectively, SjDX5-271 exhibits promising therapeutic effects in IRI and represents a novel therapeutic approach for IRI, even in immune-related diseases. This study revealed the development of a new biologic from the parasite and enhanced our understanding of host-parasite interplay, providing a blueprint for future therapies for immune-related diseases.Item A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases.(eBioMedicine, 2023-08-12) Ni, Yangyue; Xiong, Ruiyan; Zhu, Yuxiao; Luan, Ning; Yu, Chuanxin; Yang, Kun; Wang, Huiquan; Xu, Xuejun; Yang, Yuxuan; Sun, Siyu; Shi, Liyun; Chen, Lin; Chen, Lu; Hou, Min; Xu, Zhipeng; Lai, Ren; Jia, MinjunBackground: Regulatory T cells (Tregs) can alleviate the development of autoimmune and inflammatory diseases, thereby proposing their role as a new therapeutic strategy. Parasitic helminths have co-evolved with hosts to generate immunological privilege and immune tolerance through inducing Tregs. Thus, constructing a “Tregs-induction”-based discovery pipeline from parasitic helminth is a promising strategy to control autoimmune and inflammatory diseases. Methods: The gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC) were used to isolate immunomodulatory components from the egg extracts of Schistosoma japonicum. The extracted peptides were evaluated for their effects on Tregs suppressive functions using flow cytometry, ELISA and T cell suppression assay. Finally, we carried out colitis and psoriasis models to evaluate the function of Tregs induced by helminth-derived peptide in vivo. Findings: Here, based on target-driven discovery strategy, we successfully identified a small 3 kDa peptide (SjDX5-53) from egg extracts of schistosome, which promoted both human and murine Tregs production. SjDX5-53 presented immunosuppressive function by arresting dendritic cells (DCs) at an immature state and augmenting the proportion and suppressive capacity of Tregs. In mouse models, SjDX5-53 protected mice against autoimmune-related colitis and psoriasis through inducing Tregs and inhibiting inflammatory T-helper (Th) 1 and Th17 responses. Interpretation: SjDX5-53 exhibited the promising therapeutic effects in alleviating the phenotype of immune-related colitis and psoriasis. This study displayed a screening and validation pipeline of the inducer of Tregs from helminth eggs, highlighting the discovery of new biologics inspired by co-evolution of hosts and their parasites. Funding: This study was supported by the Natural Science Foundation of China (82272368) and Natural Science Foundation of Jiangsu Province (BK20211586).