Abstract Background: Chronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice. Methods: Immune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 (E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection. Result: In the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells. Conclusion: Chronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation.

Resumo Fundamentos: O modelo de hipertrofia cardíaca (HC) para ratos foi amplamente utilizado, proporcionando assim uma base de pesquisa efetiva para a exploração de HC. Objetivo: pesquisar os efeitos do modelamento de HC sob constrição da aorta abdominal (CAA) usando diferentes agulhas e pesos em ratos. Métodos: foram utilizadas quatro agulhas com diâmetros externos diferentes (0,35, 0,40, 0,45 e 0,50 mm) para CAA. Foram selecionados 150 ratos C57BL / 6 machos de acordo com o peso corporal (PC) e divididos em 3 níveis de peso: 18 g, 22 g e 26g (n = 50 em cada grupo). Todos os níveis de peso foram divididos em 5 grupos: um grupo sham (n = 10) e 4 grupos CAA usando 4 intensidades de ligadura (n = 10 por grupo). Após a cirurgia, foram registradas as taxas de sobrevivência, foi realizada ecocardiografia, os corações foram dissecados e utilizados para detecção histológica, e os dados foram analisados estatisticamente, p < 0,05 foi considerado estatisticamente significante. Resultados: Todos os ratos morreram nos seguintes grupos de CAA: 18 g/0,35 mm, 22 g/0,35 mm, 26 g/0,35 mm, 22 g/0,40 mm e 26 g/0,40 mm. Todos os ratos com CAA, aqueles ligados com uma agulha de 0,50 mm, e aqueles que sofreram operação sham sobreviveram. Ocorreram diferentes taxas de mortalidade nos seguintes grupos de CAA: 18 g/0,40 mm, 18 g/0,45 mm, 18 g/0,50 mm, 22 g/45 mm, 22 g/0,50 mm, 26 g/0,45 mm e 26 g/0,50 mm. As proporções de peso do coração/peso corporal (5,39 ± 0,85, 6,41 ± 0,68, 4,67 ± 0,37, 5,22 ± 0,42, 4,23 ± 0,28, 5,41 ± 0,14 e 4,02 ± 0,13) aumentaram significativamente em comparação com os grupos sham para ratos com os mesmos níveis de peso. Conclusão: uma agulha de 0,45mm levou a HC mais óbvia do que as agulhas de 0,40 mm e 0,50mm e causou HC extraordinária em ratos de 18 g.

Abstract Background: The cardiac hypertrophy (CH) model for mice has been widely used, thereby providing an effective research foundation for CH exploration. Objective: To research the effects of CH modeling under abdominal aortic constriction (AAC) using different needles and weights in mice. Methods: Four needles with different external diameters (0.35, 0.40, 0.45, and 0.50 mm) were used for AAC. 150 male C57BL/6 mice were selected according to body weight (BW) and divided into 3 weight levels: 18 g, 22 g, and 26 g (n = 50 in each group). All weight levels were divided into 5 groups: a sham group (n = 10) and 4 AAC groups using 4 ligation intensities (n = 10 per group). After surgery, survival rates were recorded, echocardiography was performed, hearts were dissected and used for histological detection, and data were statistically analyzed, P < 0.05 was considered statistically significant. Results: All mice died in the following AAC groups: 18g/0.35 mm, 22 g/0.35 mm, 26 g/0.35 mm, 22 g/0.40 mm, and 26 g/0.40 mm. All mice with AAC, those ligated with a 0.50-mm needle, and those that underwent sham operation survived. Different death rates occurred in the following AAC groups: 18 g/0.40 mm, 18 g/0.45 mm, 18 g/0.50 mm, 22 g/45 mm, 22 g/0.50 mm, 26 g/0.45 mm, and 26 g/0.50 mm. The heart weight/body weight ratios (5.39 ± 0.85, 6.41 ± 0.68, 4.67 ± 0.37, 5.22 ± 0.42, 4.23 ± 0.28, 5.41 ± 0.14, and 4.02 ± 0.13) were significantly increased compared with those of the sham groups for mice with the same weight levels. Conclusion: A 0.45-mm needle led to more obvious CH than did 0.40-mm and 0.50-mm needles and caused extraordinary CH in 18-g mice.

Abstract The ubiquitin-specific protease 22 (USP22) is an oncogene and its expression is upregulated in many types of cancer. In the nucleus, USP22 functions as one subunit of the SAGA to regulate gene transcription. However, the genome-wide USP22 binding sites and its direct target genes are yet clear. In this study, we characterized the potential genomic binding sites of UPS22 and GCN5 by ChIP-seq using specific antibodies in HeLa cells. There were 408 overlapping putative target genes bound by both USP22 and GCN5. Motif analysis showed that the sequences bound by USP22 and GCN5 shared two common motifs. Gene ontology (GO) and pathway analysis indicated that the genes targeted by USP22 and GCN5 were involved in different physiological processes and pathways. Further RNA-seq, GO and pathway analyses revealed that knockdown of UPS22 induced differential expression of many genes that participated in diverse physiological processes, such as metabolic process. Integration of ChIP-seq and RNA-seq data revealed that UPS22 bound to the promoters of 56 genes. These findings may provide new insights into the regulation of USP22 on gene expression during the development of cervical cancer.

Background and Objectives: Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in serotonin biosynthesis in the nervous system. Several variants of human TPH2 have been reported to be associated with a spectrum of neuropsychiatric disorders such as unipolar major depression, bipolar disorder and suicidality etc. Recent studies suggested that two variants (T212 and A375) in the exon 7 and exon 9 were associated with major depressive disorder (MDD). Methods: To replicate these findings, two polymorphisms located in exons 7 and 9 of TPH2 (rs7305115 and rs4290270, respectively) were analysed by DNA sequence in the case-control sample study in 191 MDD and 191 healthy volunteers. Statistical analyses were carried out using the program SPSS. The comparison of allele and genotype frequencies of each polymorphism between case and control groups was carried out on the online software SHEsis. All subjects were unrelated southern Han Chinese. Results: No difference was observed on the allelic or genotypic distribution of TPH2 gene polymorphisms between the groups. However, the two-marker haplotype covering components T212 (rs7305115) A and A375 (rs4290270) T were observed to have a significantly protective effect MDD in female (corrected p = 0.0032; OR = 0.241[95% CI = 0.099-0.587]). Conclusions: The results suggest that TPH2 might be associated with a lower risk of female MDD. However, confirmatory studies in independent samples are needed.