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Objectives: Given the limited research and its potential hazards, the study aimed to determine the prevalence of Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R. conorii), a tick-borne disease, in Yunnan Province, China., Methods: Through stratified sampling across five distinct regions in Yunnan, 5358 blood samples were obtained from the general healthy population. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Polymerase chain reaction (PCR) were employed for analysis., Results: IFA identified 27 (0.50%) subjects with immunoglobulin G (IgG) positivity; none were positive for immunoglobulin M (IgM) via ELISA. PCR detected one individual with R. conorii outer membrane protein A (ompA). Significant seroprevalence variation was observed, particularly in Southern Yunnan (P = 0.032), with R. conorii subsp. conorii confirmed in the PCR-positive sample., Conclusions: This research reveals a correlation between MSF prevalence, geography, and climate in Yunnan. The paucity of prior studies underscores MSF's potential diagnostic challenges in the region. Comprehensive understanding of the pathogen's distribution is pivotal for intervention. Given the study's scope and Yunnan's unique setting, additional research is advocated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Lyme disease is a zoonotic disease caused by infection with Borrelia burgdorferi (Bb), the involvement of the nervous system in Lyme disease is usually referred to as Lyme neuroborreliosis (LNB). LNB has diverse clinical manifestations, most commonly including meningitis, Bell's palsy, and encephalitis. However, the molecular pathogenesis of neuroborreliosis is still poorly understood. Comprehensive transcriptomic analysis following Bb infection could provide new insights into the pathogenesis of LNB and may identify novel biomarkers or therapeutic targets for LNB diagnosis and treatment., Methods: In the present study, we pooled transcriptomic dataset of Macaca mulatta (rhesus) from our laboratory and the human astrocyte dataset GSE85143 from the Gene Expression Omnibus database to screen common differentially expressed genes (DEGs) in the Bb infection group and the control group. Functional and enrichment analyses were applied for the DEGs. Protein-Protein Interaction network, and hub genes were identified using the Search Tool for the Retrieval of Interaction Genes database and the CytoHubba plugin. Finally, mRNA expression of hub genes was validated in vitro and ex vivo from Bb infected models and normal controls by quantitative reverse transcription PCR (qRT-PCR)., Results: A total of 80 upregulated DEGs and 32 downregulated DEGs were identified. Among them, 11 hub genes were selected. The pathway enrichment analyses on 11 hub genes revealed that the PI3K-Akt signaling pathway was significantly enriched. The mRNA levels of ANGPT1, TLR6, SREBF1, LDLR, TNC, and ITGA2 in U251 cells and/or rhesus brain explants by exposure to Bb were validated by qRT-PCR., Conclusion: Our study suggested that TLR6, ANGPT1, LDLR, SREBF1, TNC, and ITGA may be candidate mammal biomarkers for LNB, and the TLR6/PI3K-Akt signaling pathway may play an important role in LNB pathogenesis., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Certain natural products, derived from medicinal plants, exhibit anti-inflammatory properties, but the mechanism of action of many remains unclear. Borrelia burgdorferi spirochetes are responsible for causing Lyme arthritis through activation of the Toll-like receptor (TLR) signaling pathway. In this study, we investigated the mechanisms by which Isoforskolin (ISOF) and Cucurbitacin IIa (CuIIa), compounds derived from Chinese herbs, can exert anti-inflammatory effects by modulating single immunoglobulin interleukin-1 receptor-related receptor (SIGIRR; also known as Toll/interleukin-1 receptor 8, TIR8) and thereby inhibiting B. burgdorferi basic membrane protein A (BmpA)-induced TLR signaling in human macrophages, specifically the THP-1 human monocytic cell line. After THP-1 cells were exposed in vitro to: i) recombinant (r)BmpA, ii) rBmpA and ISOF or iii) rBmpA and CuIIa, Cytotoxicity assay (Cell Counting Kit-8, CCK-8) are used to measure the effects of ISOF and CuIIa on cell viability. Meanwhile, real-time polymerase chain reaction and Western blotting were used to quantify SIGIRR mRNA and protein levels, respectively, at 6, 12, 24 and 48 h time points post-stimulation. In addition, proinflammatory cytokine tumor necrosis factor-α (TNF-α) was determined by ELISA analysis. Our study showed that rBmpA stimulation of THP-1 cells resulted in a drop in SIGIRR levels in THP-1 cells. More importantly, SIGIRR levels increased significantly in rBmpA-stimulated THP-1 cells following ISOF or CuIIa administration, and the results of ELISA analysis suggested that ISOF or CuIIa reduced the secretion of the proinflammatory cytokine TNF-α. In conclusion, These results reveal new possibilities for the treatment of Lyme arthritis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)