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Krooniset bakteeri-infektiot (Luettu 216657 kertaa)
HopeSprings
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Re: Krooniset bakteeri-infektiot
Vastaus #345 - 08.09.2018 - 01:37:21
 
STAT3 can be a therapeutic target for chronic active EBV infection, a fatal disorder

https://www.sciencedaily.com/releases/2018/08/180820113117.htm

August 20, 2018
Tokyo Medical and Dental University(TMDU) study shows that ruxolitinib-induced inhibition of STAT3 activity blocks survival and reduces pro-inflammatory cytokine production in Epstein-Barr virus (EBV)-infected clonally proliferating T- or NK-cells in Chronic active Epstein-Barr virus infection.

Tokyo, Japan -- Chronic active Epstein-Barr virus infection (CAEBV) is an EBV-positive T- or NK-cell neoplasm accompanied by sustained systemic inflammation. Many studies have attempted to understand the case of CAEBV; none have provided a clear explanation, until now.

A research team, led by experts from Tokyo Medical and Dental University(TMDU), investigated the activity of STAT3, a factor that helps to control cell proliferation and survival, in EBV-infected T- or NK-cells in CAEBV. They found that STAT3 was constitutively activated in those cells, reported in Oncotarget, "STAT3 is constitutively activated in chronic active Epstein-Barr virus infection and can be a therapeutic target."

CAEBV is a disorder which has 2 aspects: an inflammatory disorder and a lymphoid neoplasm. During the course, it may progress to chemotherapy-resistant lymphoma or leukemia, or to a life-threatening disorder known as hemophagocytic lymphohistiocytosis. Despite a variety of efforts to control or cure CAEBV, the sole effective treatment has been stem cell transplantation from a HLA-matched donor. Unfortunately, some patients cannot be candidates for this therapy, and there are many side effects.

"Constitutively activated STAT3 has been observed in a variety of primary tumor cells, including other tumors associated with Epstein-Barr virus infection," says Ayoko Arai, corresponding author on the study. "We suspected that STAT3 may be similarly activated in cells from patients with CAEBV."

In the study, increased phosphorylation, an important modification of cellular proteins, was observed on STAT3 in EBV-infected T- or NK-cells from patients with CAEBV. In those same cells from health individuals, the phosphorylation was absent, suggesting that it may provide a useful drug target.

"Our analyses revealed no mutations in STAT3, so we tested whether inhibitors of STAT3 phosphorylation might modify its activity in laboratory-grown," says Erika Onozawa, lead author on the study. "We found that ruxolitinib, a drug that is currently used for treatment of myelofibrosis and polycythemia vera, could suppress the survival of the EBV-infected cells in a dose-dependent manner."

In addition to the ability of ruxolitinib to induce the death of virus-infected T- or NK-cells from patients with CAEBV, the researchers showed that it could block the production of several important inflammatory cytokines that play a role in the progression of CAEBV.

CAEBV is a neoplastic and inflammatory disease that can become extremely destructive for some patients. This study showed that STAT3 could be an important new target for treatment of this disorder, and that ruxolitinib may provide a readily available therapy that may be effectively used in clinical treatment.
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HopeSprings
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Re: Krooniset bakteeri-infektiot
Vastaus #346 - 02.10.2018 - 18:42:50
 
Multiple sclerosis and mixed microbial infections. Direct identification of fungi and bacteria in nervous tissue.

https://www.ncbi.nlm.nih.gov/pubmed/29859870

Abstract

Multiple sclerosis (MS) is the prototypical inflammatory disease of the central nervous system (CNS), leading to multifocal demyelination and neurodegeneration. The etiology of this incurable disease is unknown and remains a matter of intensive research. The possibility that microbial infections, such as viruses or bacteria, can trigger an autoimmune reaction in CNS tissue has been suggested. However, the recent demonstration that bacteria are present in CNS tissue points to a direct involvement of microbial infections in the etiology of MS. In the present study, we provide the first evidence of fungal infection in CNS tissue of MS patients, and demonstrate that fungal DNA from different species can be detected in the CNS. We used, nested PCR assays together with next-generation sequencing to identify the fungal species in the nervous tissue of 10 patients with MS. Strikingly, Trichosporon mucoides was found in the majority of MS patients, and particularly high levels of this fungus were found in two patients. Importantly, T. mucoides was not detected in the CNS of control subjects. We were also able to visualize fungal structures in CNS tissue sections by immunohistochemistry using specific antifungal antibodies, which also revealed the accumulation of a number of microbial cells in microfoci. Again, microbial structures were not observed in CNS sections from controls. In addition to fungi, neural tissue from MS patients was also positive for bacteria. In conclusion, our present observations point to the novel concept that MS could be caused by polymicrobial infections. Thus, mycosis of the CNS may be accompanied by opportunistic bacterial infection, promoting neuroinflammation and directly causing focal lesions, followed by demyelination and axonal injury.
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