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        Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition

        Xian Wang,Shaolei Ma,Haibo Wu,Xiaofeng Shen,Shiqin Xu,Xirong Guo,Maria L Bolick,Shizheng Wu,Fuzhou Wang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

        Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory. Correspondingly, dopamine (DA) content shows the reverse characteristic change to MIF with a time-dependent curve in post-surgical behavior. The levels of both MIF and DA are reversed by the MIF tautomerase inhibitor ISO-1, and a negative relationship exists between MIF and DA. The reversed role of ISO-1 also affects tyrosine hydroxylase expression. Furthermore, CCI induces Th promoter CpG site methylation in the L-SC and VTA areas, and this effect could be abated by ISO-1 administration. G9a/SUV39H1 and H3K9me2/H3K9me3 enrichment within the Th promoter region following CCI in the L-SC and VTA was also decreased by ISO-1. In cultured dopaminergic neurons, rMIF enhanced the recruitment of G9a and SUV39H1, followed by an increase in H3K9me2/H3K9me3. These molecular changes correspondingly exhibited alterations in Th promoter CpG site methylation and pain behaviors. In summary, MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.

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        Diagnosing Balamuthia mandrillaris amebic meningoencephalitis in a 64-year-old woman from the Southwest of China

        Yao Suhua,Chen Xiaoting,Qian Lian,Sun Shizheng,Zhao Chunjing,Bai Zongkai,Chen Zhaofang,Wu Youcong 대한기생충학ㆍ열대의학회 2023 The Korean Journal of Parasitology Vol.61 No.2

        Balamuthia mandrillaris amebic encephalitis (BAE) can cause a fatal condition if diagnosis is delayed or effective treatment is lacking. Patients with BAE have been previously reported in 12 provinces of China, with skin lesions being the primary symptom and encephalitis developing after several years. However, a significantly lower number of cases has been reported in Southwest China. Here we report an aggressive BAE case of a 64-year-old woman farmer with a history of skin lesions on her left hand. She was admitted to our hospital due to symptoms of dizziness, headache, cough, vomiting, and gait instability. She was initially diagnosed with syphilitic meningoencephalitis and received a variety of empirical treatment that failed to improve her symptoms. Finally, she was diagnosed with BAE combined with amebic pneumonia using next-generation sequencing (NGS), qRT-PCR, sequence analysis, and imaging studies. She died approximately 3 weeks after the onset. This case highlights that the rapid development of encephalitis can be a prominent clinical manifestation of Balamuthia mandrillaris infection.

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