The key to arthritis management is early diagnosis and treatment to prevent further joint destruction and maximize functional ability. Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common types of arthritis that the primary care provider must differentiate, in terms of diagnosis and treatment. Effective and non-invasive strategies for early detection and disease identification are sorely needed. Growing evidence suggests that RA has a correlation with oral microbiome and may be affected by its dynamic variations. There is already a study comparing oral microbiome in patients with RA and OA, however, it did not screen for potential biomarkers for arthritis. In this study, we assessed the oral microbiome in saliva samples from 110 RA patients, 67 OA patients and 155 healthy subjects, using 16S rRNA gene amplicon sequencing. The structure and differences in oral microbiome between RA, OA and healthy subjects were analyzed. Eight oral bacterial biomarkers were identified to differentiate RA from OA. This report provides proof of oral microbiota as an informative source for discovering non-invasive biomarkers for arthritis screening.

Abstract. Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions. In addition, IL-37 may prove to be a new and potentially useful target for effective cytokine therapy. Further evidence is needed to clarify in more detail the effects of IL-37 in experimental and clinical studies. Based on an extensive summary of published data, the aim of this review is to outline the current knowledge of IL-37, including the location, structure, expression, regulation and function, as well as the potential clinical applications of this cytokine.

Human intestinal microbes can mediate development of arthritis – Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be involved in arthritis, although the underlying mechanism remains unclear. To characterize potential SF bacterial nucleic acids, we used 16S rRNA gene amplicon sequencing to assess bacterial nucleic acid communities in 15 synovial tissue (ST) and 110 SF samples from 125 patients with rheumatoid arthritis (RA) and 16 ST and 42 SF samples from 58 patients with osteoarthritis (OA). Our results showed an abundant diversity of bacterial nucleic acids in these clinical samples, including presence of Porphyromonas and Bacteroides in all 183 samples. Agrobacterium, Comamonas, Kocuria, Meiothermus, and Rhodoplanes were more abundant in synovial tissues of rheumatoid arthritis (STRA). Atopobium, Phascolarctobacterium, Rhodotorula mucilaginosa, Bacteroides uniformis, Rothia, Megasphaera, Turicibacter, Leptotrichia, Haemophilus parainfluenzae, Bacteroides fragilis, Porphyromonas, and Streptococcus were more abundant in synovial tissues of osteoarthritis (STOA). Veillonella dispar, Haemophilus parainfluenzae, Prevotella copri and Treponema amylovorum were more abundant in synovial fluid of rheumatoid arthritis (SFRA), while Bacteroides caccae was more abundant in the synovial fluid of osteoarthritis (SFOA). Overall, this study confirms existence of bacterial nucleic acids in SF and ST samples of RA and OA lesions and reveals potential correlations with degree of disease.

Glioma is characterized by a high recurrence rate, short survival times, high rates of mortality and treatment difficulties. Surgery, chemotherapy and radiation (RT) are the standard treatments, but outcomes rarely improve even after treatment. With the advancement of molecular pathology, recent studies have found that the development of glioma is closely related to various epigenetic phenomena, including DNA methylation, abnormal microRNA (miRNA), chromatin remodeling and histone modifications. Owing to the reversibility of epigenetic modifications, the proteins and genes that regulate these changes have become new targets in the treatment of glioma. In this review, we present a summary of the potential therapeutic targets of glioma and related effective treating drugs from the four aspects mentioned above. We further illustrate how epigenetic mechanisms dynamically regulate the pathogenesis and discuss the challenges of glioma treatment. Currently, among the epigenetic treatments, DNA methyltransferase (DNMT) inhibitors and histone deacetylase inhibitors (HDACIs) can be used for the treatment of tumors, either individually or in combination. In the treatment of glioma, only HDACIs remain a good option and they provide new directions for the treatment. Due to the complicated pathogenesis of glioma, epigenetic applications to glioma clinical treatment are still limited.

Background: Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, however, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is also no report on the relationship between immunocytochemistry markers and salivary microbiota.Method: In this study, we assessed the salivary microbiome of 75 non-smoking female lung cancer patients and 172 matched healthy individuals using 16S rRNA gene amplicon sequencing. We also calculated the Spearman's rank correlation coefficient between salivary microbiota and three immunohistochemical markers (TTF-1, Napsin A and CK7).Result: We analyzed the salivary microbiota of 247 subjects and found that non-smoking female lung cancer patients exhibited oral microbial dysbiosis. There was significantly lower microbial diversity and richness in lung cancer patients when compared to the control group (Shannon index, P < 0.01; Ace index, P < 0.0001). Based on the analysis of similarities, the composition of the microbiota in lung cancer patients also differed from that of the control group (r = 0.454, P < 0.001, unweighted UniFrac; r = 0.113, P < 0.01, weighted UniFrac). The bacterial genera Sphingomonas (P < 0.05) and Blastomonas (P < 0.0001) were relatively higher in non-smoking female lung cancer patients, whereas Acinetobacter (P < 0.001) and Streptococcus (P < 0.01) were higher in controls. Based on Spearman's correlation analysis, a significantly positive correlation can be observed between CK7 and Enterobacteriaceae (r = 0.223, P < 0.05). At the same time, Napsin A was positively associated with genera Blastomonas (r = 0.251, P < 0.05). TTF-1 exhibited a significantly positive correlation with Enterobacteriaceae (r = 0.262, P < 0.05). Functional analysis from inferred metagenomes indicated that oral microbiome in non-smoking female lung cancer patients were related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis.Conclusions: The study identified distinct salivary microbiome profiles in non-smoking female lung cancer patients, revealed potential correlations between salivary microbiome and immunocytochemistry markers used in clinical diagnostics, and provided proof that salivary microbiota can be an informative source for discovering non-invasive lung cancer biomarkers.

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Despite advances in treatment modalities, 5-year survival among glioma patients remains poor. Glioma cancer stem cells (CSCs) exhibit high tumorigenic activity and are associated with resistance to treatment and tumor recurrence. Because overexpression of toll-like receptor 4 (TLR4) correlated with cancer development, we investigated LPS-induced TLR4 signaling in glioma CD133-positive (CD133+) CSCs. The proliferation of CD133+ CSCs isolated from CSCs derived from the U251 and SF295 glioma cell lines and from human glioma samples was upregulated on a time- and concentration-dependent basis by LPS stimulation, with increases in CD133, NANOG, and NESTIN mRNA and protein levels. Also elevated was cytokine expression, which was coupled to phosphorylation of mitogen-activated protein kinase, and activation of cyclins and cyclin-dependent kinase complexes. TLR4 knockdown reduced LPS-induced CD133+ CSC proliferation, whereas Adriamycin-induced CD133+ CSC apoptosis was moderately inhibited by treatment with LPS, implying a protective effect of LPS. The capacity of glioma CD133+ CSC-reactive cytotoxic T lymphocyte to selectively kill CD133+ CSCs was reduced by LPS, and this effect was not apparent after TLR4 knockdown in CD133+ CSCs. These data suggest TLR4 signaling is a factor in CD133+ CSC immune evasion, and thus disruption of TLR4 signaling is a potential therapeutic strategy in glioma.

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