Hepatocellular carcinoma (HCC) remains a major challenge to clinicians due to its unacceptably high mortality and morbidity. The etiology of HCC is multi-faceted, including viral infection, alcoholism and non-alcoholic fatty liver disease. Dysregulated host immunity contributes to tumorigenesis among these susceptible individuals with pre-existing condition(s). IL-32 and IL-34 are key cytokines driving the development of chronic inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, as well as chronic liver diseases. IL-32 and IL-34 play an important role augmenting the development of HCC, due to their direct influence over host inflammation, however, new roles for these cytokines in HCC are emerging. Here we comprehensively review the latest research for IL-32 and IL-34 in HCC, identifying a subset of potential therapeutic targets for use in precision medicine.
<p>Figure S1. The promoter CpG island of TRPM3/miR-204 is hypermethylation in CRC cells. A, Target sequences in the promote CpG islands of miR-638 gene used for the DNA methylation analysis. The underlined sequences are regions corresponding to the primers of bisulfite-sequencing PCR (BSP) used. B, Schematic representation of the methylation status of the CpG island (including 42 CpG sites) in the TRPM3 promoter as detected in the indicated CRC cell lines. Circles mark different CpG sites in the analyzed sequence. C, The relative mRNA levels of TRPM3 in CRC cell lines. Normal, a pooled sample of noncancerous tissues (NCTs). D, The relative expression of miR-204-5p in CRC cell lines. E, The TRPM3 mRNA levels in CRC cell lines were positively correlated with those of miR-204-5p. F, Quantitative analysis of miR-204-5p expression in CRC cells treated with DNA methyltransferase inhibitor (5-aza-dC). Following treatment of HCT116 and LoVo cells with 5-aza-dC for 72 hours, the miR-204-5p expression in the treated CRC cells was significantly increased compared with untreated control cells (***P < 0.001).</p>
CRISPR technology has rapidly changed the face of biological research, such that precise genome editing has now become routine for many labs within several years of its initial development. CRISPR/Cas9 (Clustered Regularly Interspace Short Palindromic Repeat/CRISPR-associated nuclease 9) gene editing system is a powerful and groundbreaking programmable genome editing technology developed based on an adaptive bacterial and archaea immune system resisting the invasion of exogenous nucleic acid. Compared with traditional genome editing technology, CRISPR/Cas9 system is easier, efficient and less cytotoxic. CRISPR/Cas9 gene editing technology has been applied to many aspects of cancer research, including research on tumor genes, constructing animal tumor models, screening tumor phenotypic-related and resistance-associated gene and cancer gene therapy. In this review, we focus on the application of the CRISPR screen for this fast moving field. Finally, we discuss practical aspects of screen design, and outline a further step forward in the rapidly expanding field of genome editing.
ABSTRACT Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease, and its clinical manifestations are closely related to the dysregulation of inflammatory factors. Nonsteroidal anti-inflammatory drugs have been shown to be effective in managing inflammation and providing pain relief, but their clinical application remains controversial. Traditional Chinese medicine (TCM) is widely used to regulate inflammatory factors in CP/CPPS, and treatment with TCM has gained some advantages based on an “individualized” or “personalized” medical approach. In addition, TCM extracts and acupuncture therapy have also been proven to be effective for CP/CPPS, as they regulate related inflammatory factors. However, current systematic reviews tend to verify the efficacy and safety of TCM therapies in CP/CPPS, and there is still a deficiency in sorting out their mechanisms of modulating inflammatory factors. Based on the current evidence, our review summarizes the application of TCM in regulating inflammatory factors in CP/CPPS to provide a reference for the treatment of CP/CPPS with TCM therapy and a potential direction with future studies in this field.
Animals modulate sleep in accordance with their internal and external environments. Metabolic cues are particularly potent regulators of sleep, allowing animals to alter their sleep timing and amount depending on food availability and foraging duration. The fruit fly,
To identify the phenotypic detection and structure analysis of a protein C (PC) missense mutation (Met406Ile) resulting in venous thromboembolism.Pedigree research was performed for a hereditary PC deficiency pedigree. Chromogenic assay was used for phenotypic diagnosis to detect the AT activity. All 9 exons were amplified by polymerase chain reaction (PCR) and direct sequencing analysis was performed for PCR products. The corresponding mutation sites of family members were detected.Homology modeling was used for reconstructing mutant PC construction. The effects of construction change were analyzed.The PC activities of proband and 4 family members decreased to different extents by 29.7%, 42.2%, 42.4%, 67.3% and 70.7% respectively. Among them, the proband and other three family members carried the same mutation (c.1218G > A, Met406Ile) while another family member had a PC polymorphism (rs1799810). Homology modeling showed that VDW's interaction radius of amino acids decreased after mutation (Met406Ile).In particular, the radius of Gly418:C and Ile406CG2, Gly418:C and Ile406HG23, Leu419:N and Ile406:HG23 decreased to 2.0733å, 1.620 45å and 1.446 52å respectively. Compared with normal PC, the interaction energy of mutant PC rose from -8.504 54 to 1210.04 kal/mol. And the change of VDW interaction energy was significant.The mechanism of this pedigree is caused by PROC gene missense mutation on exon 9 (c.1218G > A, Met406Ile). The regional amino acids of mutant PC collide with each other and lead to an instability of PC reconstruction.
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