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hors. The Journal of Physiology © 2020 The Physiological Society.The co-evolving tumour cells and the systemic immune environment are mutually dysregulated. Tumours affect the immune response in a complex manner. For example, while lymphocytes are mobilized in response to tumours, their function is impaired by tumour progression. This study aimed to explore how the baseline and dynamic renal cell carcinoma (RCC) tumour burdens affect the T cell repertoire, and whether the baseline T cell receptor β chain (TCRB) diversity predicts prognosis. To characterise the TCRB repertoire, the baseline and follow-up peripheral TCRB repertoires of 45 RCC patients and two benign renal disease patients were examined using high-throughput TCRB sequencing. To explain the significance of TCRB diversity, 56 peripheral leukocyte samples from 28 patients before and after surgery were subjected to transcriptome sequencing. To validate the results, an advanced RCC patient repertoire was subjected to single cell RNA sequencing (scRNA, 10x Genomics). Higher TCRB diversity was found to be correlated with a higher lymphocyte-to-neutrophil ratio, especially indicating more naïve T cells. High baseline TCRB diversity predicted a better prognosis for stage IV patients, and different tumour burdens exerted distinct impacts on the immune status. The pre-operative TCRB diversity was significantly higher in benign and stage I (low tumour burden) RCC patients than in stage IV (high tumour burden) patients. After the tumour burden of advanced patients was mostly relieved, we observed that the TCRB diversity was restored, T cell exhaustion was reduced, and naïve T cells mobilized. It was demonstrated that the circulating TCRB repertoire could reflect the immune status and predict prognosis, and to some extent that cytoreductive nephrectomy (CN) reduces the burden of the immune system in advanced patients, which might provide a good opportunity for immunotherapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Previously we reported that the microRNA miR-210 is aberrantly upregulated in clear cell renal cell carcinoma (ccRCC) via deregulation of the VHL-HIF pathway. In the present study, to investigate the biological impact of miR-210 in ccRCC tumorigenesis, we developed a transgenic mouse line expressing miR-210 in proximal tubule cells under control of the mouse SGLT2/Slc5a2 promoter. Light microscopy revealed desquamation of the tubule cells and regeneration of the proximal tubule, suggesting that miR-210 expression led to damage of the proximal tubule cells. Electron microscopy revealed alterations to the mitochondria in proximal tubule cells, with marked reduction of the mitochondrial inner membrane, which is the main site of ATP production via oxidative phosphorylation. An additional in vitro study revealed that this loss of the inner membrane was associated with downregulation of Iscu and Ndufa4, the target genes of miR-210, suggesting that the miR-210-ISCU/NDUFA4 axis may affect mitochondrial energy metabols. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Capicua, encoded by the gene CIC, is an evolutionarily conserved high-mobility group-box transcription factor downstream of the receptor tyrosine kinase and mitogen-activated protein kinase pathways. It was initially discovered and studied in Drosophila. Recurrent mutations in CIC were first identified in oligodendroglioma, a subtype of low-grade glioma. Subsequent studies have identified CIC aberrations in multiple types of cancer and have established CIC as a potent tumour suppressor involved in regulating pathways related to cell growth and proliferation, invasion and treatment resistance. The most well-known and studied targets of mammalian CIC are the oncogenic E-Twenty Six transcription factors ETV1/4/5, which have been found to be elevated in cancers with CIC aberrations. Here, we review the role of CIC in normal mammalian development, oncogenesis and tumour progression, and the functional interactors that mediate them. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Multiple sclerosis (MS) is a chronic disease of the CNS, hallmarked by inflammation and demyelination. Selleckchem Butyzamide Early stages of the disease frequently show active lesions containing numerous foamy macrophages and inflammatory cells. Disease progression is highlighted by increasing numbers of mixed active/inactive or inactive lesions showing sparse inflammation and pronounced astrogliosis. Furthermore, gray matter lesions increase in number and extent during disease progression. MicroRNAs (miRNAs) comprise a group of several thousand (in humans more than 2000), small non-coding RNA molecules with a fundamental influence on about one-third of all protein-coding genes. Furthermore, miRNAs have been detected in body fluids, including spinal fluid, and they are assumed to participate in intercellular communications. Several studies have determined miRNA profiles from dissected white and gray matter lesions of autoptic MS patients. In this review, we summarize in detail the current knowledge of individual miRNAs in gray and white matter lesions of MS patients and present the concepts of MS tissue lesion development based on the altered miRNA profiles. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.The interdigital glands of sheep perform various functions including those pertaining to sexual behaviors. Morphological and histological structure of the gland demonstrates differences among species. The aim of this study is to examine the morphological and histological structure of Hasak and Hasmer sheep's interdigital glands and to determine the differences with other sheep breeds. For this research, we selected 7 Hasak and 7 Hasmer female sheep. After scarification, the feet were obtained and used for anatomical and histological examinations. For the histological examination, the interdigital gland tissues were stained with Crossman modified triple, Periodic acid Schiff (PAS) and Alcian blue (AB) staining. The morphometric analysis results, mean values of weight, body length, body diameter, flexura, ductus length, ductus diameter, were observed as 0.80mm, 14.61mm, 5.98mm, 5.62mm, 26.58mm and 3.25mm respectively in Hasak and 0.8mm, 15.46mm, 6.37mm, 5.70mm, 24.52 and 3.52 in Hasmer sheep. The histochemical staining revealed that the apocrine secretion of this gland was PAS positive and AB negative.