The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration. We conclude with a discussion of the possible therapeutic strategies for modulating splenic abnormalities, including the novel potential usage of nanomedicine in non-surgically targetting splenic disorders for the treatment of liver cirrhosis.

Background: Deemed as a member of malignant tumors, hepatocellular carcinoma (HCC) has been characterized as a lethal disease with high morbidity and mortality. It has been widely accepted that long noncoding RNAs (lncRNAs) play a big part in the complicated biologic processes of cancer. Aim of the study: The purpose of the study is to figure out the role and molecular regulation mechanism of ST8SIA6-AS1 in HCC. Methods: The role of ST8SIA6-AS1 in HCC was validated by RT-qPCR, colony formation, ki-67 detection, TUNEL, JC-1 detection, wound healing and transwell-invasion assays, furthermore, the binding ability between ST8SIA6-AS1/HOXB6 and miR-5195-3p were confirmed by RNA pull down and luciferase reporter assays. Besides, the regulatory mechanism of ST8SIA6-AS1 to HOXB6/miR-5195-3p was measured by RT-qPCR and western blot assays. Results: We measured that ST8SIA6-AS1 was highly expressed in HCC cell lines. Then knockdown of it suppressed cell proliferation, migration and migration but activated cell apoptosis in HCC. Furthermore, ST8SIA6-AS1 could bind with miR-5195-3p and negatively regulated its expression in HCC. Subsequently, it confirmed that HOXB6 was target gene of miR-5195-3p and positively modulated by ST8SIA6-AS1 in HCC. Finally, we verified that miR-5195-3p deficiency or HOXB6 upregulation countervailed the repressing effects of ST8SIA6-AS1 depletion on HCC progression. Conclusions: To sum up, ST8SIA6-AS1 promotes HCC progression by absorbing miR-5195-3p to regulate HOXB6, which might provide some worthy suggestions to research the development process of HCC.

Introduction: Portal hypertension combined with hypersplenism (PHcH) is the main cause of hypocytosis and esophagogastric variceal hemorrhage in patients with liver cirrhosis. Activated macrophages that destroy excess blood cells are the main cause of hypersplenism, but the activating pathway is not very clear. This study aims to investigate the activation types of splenic macrophages and their activation mechanisms, to provide experimental evidence for the biological treatment of splenomegaly, and to find a strategy to improve liver fibrosis and inflammation by intervening in splenic immune cells. This study revealed the occurrence of M2-like polarization of macrophages and upregulation of c-Myc gene expression in the PH spleen.Methods: RNAseq, protein chip, western blot, and chip-seq were performed on macrophages and the in vitro MEK inhibitor rafametinib was used. Carbon tetrachloride and thioacetamide induced mouse cirrhosis models were separately constructed.Results: c-Myc gene knockout in splenic macrophages reduced M2-like polarization and exacerbated liver fibrosis inflammation. c-Myc activated the MAPK signaling pathway and upregulated the expression of IL-4 and M2-like related genes in PH hypersplenism through the MEK-ERK-c-Myc axis. In addition, the c-Myc gene exerted anti-inflammatory effects by upregulating IL-4-mediated signal transduction to promote M2-like differentiation and anti-inflammatory cytokine secretion.Conclusions: Activation of MEK‐ERK‐c‐MYC signaling pathway promotes splenic M2-like macrophage polarization to inhibit PHcH-liver cirrhosis. Therefore, the induction of macrophage depolarization might represent a new therapeutic approach in the cure of PH hypersplenism, making c-Myc a potential candidate for macrophage polarization therapy.

Background: The use of gene development data from public database has become a new starting point to explore mitochondrial related gene expression and construct a prognostic prediction model of ovarian cancer.Methods: Data were obtained from the TCGA and ICGC databases, and the intersection with mitochondrial genes was used to obtain the differentially expressed genes. q-PCR, Cox proportional risk regression, minimal absolute contraction and selection operator regression analysis were performed to construct the prognostic risk model, and ROC curve was used to evaluate the model for centralized verification. The association between risk scores and clinical features, tumor mutation load, immune cell infiltration, macrophage activation analysis, immunotherapy, and chemosensitivity was further evaluated.Results: A prognostic risk score model for ovarian cancer patients was constructed based on 12 differentially expressed genes. The score was highly correlated with ovarian cancer macrophage infiltration and was a good predictor of the response to immunotherapy. M1 and M2 macrophages in the ovarian tissue in the OV group were significantly activated, providing a reference for the study of the polarity change of tumor-related macrophages for the prognosis and treatment of ovarian cancer. In terms of drug sensitivity, the high-risk group was more sensitive to vinblastine, Acetalax, VX-11e, and PD-0325901, while the low-risk group was more sensitive to Sabutoclax, SB-505124, cisplatin, and erlotinib.Conclusion: The prognostic risk model of ovarian cancer associated to mitochondrial genes built on the basis of public database better evaluated the prognosis of ovarian cancer patients and guided individual treatment.