Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Limitations and modifications in the clinical application of calcium sulfate.

Calcium sulfate and calcium sulfate-based biomaterials have been widely used in non-load-bearing bone defects for hundreds of years due to their superior biocompatibility, biodegradability, and non-toxicity. However, lower compressive strength and rapid degradation rate are the main limitations in clinical applications. Excessive absorption causes a sharp increase in sulfate ion and calcium ion concentrations around the bone defect site, resulting in delayed wound healing and hypercalcemia. In addition, the space between calcium sulfate and the host bone, resulting from excessively rapid absorption, has adverse effects on bone healing or fusion techniques. This issue has been recognized and addressed. The lack of sufficient mechanical strength makes it challenging to use calcium sulfate and calcium sulfate-based biomaterials in load-bearing areas. To overcome these defects, the introduction of various inorganic additives, such as calcium carbonate, calcium phosphate, and calcium silicate, into calcium sulfate is an effective measure. Inorganic materials with different physical and chemical properties can greatly improve the properties of calcium sulfate composites. For example, the hydrolysis products of calcium carbonate are alkaline substances that can buffer the acidic environment caused by the degradation of calcium sulfate; calcium phosphate has poor degradation, which can effectively avoid the excessive absorption of calcium sulfate; and calcium silicate can promote the compressive strength and stimulate new bone formation. The purpose of this review is to review the poor properties of calcium sulfate and its complications in clinical application and to explore the effect of various inorganic additives on the physicochemical properties and biological properties of calcium sulfate.

Correlation investigation between a single nucleotide polymorphism in ADAMTS14 (rs4747096) and osteoarthritis: a meta-analysis.

BACKGROUND: Current evidence of the association between a single nucleotide polymorphism (SNP) in ADAMTS14 (rs4747096) and osteoarthritis (OA) is controversial. This study aimed to determine whether the ADAMTS14 SNP is closely related to OA risk. METHODS: An electronic search of for the association between the rs4747096 polymorphisms and OA was performed using four online databases (updated on September 10, 2022). The association between susceptibility to OA and rs4747096 polymorphism was evaluated in four genetic models: the allele (mutation [A] vs. wild type [G]), additive (AA vs. GG and AG vs. GG), recessive (AA vs. AG + GG), and dominant (AA + AG vs. GG). This meta-analysis was performed in the R software, and effects were assessed using odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Four studies (707 cases in the case group and 859 cases in the control group) were included. The results of the meta-analysis showed that, except in the recessive genetic model, there was a significant correlation between OA risk and the rs4747096 polymorphism using the allele (OR [95% CI] = 1.48 [1.26-1.73], P < 0.001), additive (AG vs. GG, OR [95% CI] = 2.56 [1.79-3.65], P < 0.001; AA vs. GG, OR [95% CI] = 2.81 [1.98-3.98], P < 0.001), and dominant (OR [95% CI)] = 1.72 [1.34-2.2], P < 0.001) genetic models. CONCLUSIONS: The ADAMTS14 rs4747096 polymorphism is associated with susceptibility to OA.

Dysregulation of miR-301a-3p serves as a non-invasive biomarker and is associated with inflammatory responses in traumatic spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) led by trauma is a serious damage in central nervous system. This study aimed at confirming the expression levels and clinical significance of miRNA-301a-3p (miR-301a-3p) in SCI patients, and exploring the potential mechanisms of miR-301a-3p participating in SCI progression. METHODS: One hundred and thirty nine acute spinal trauma patients, included neurologically normal, incomplete and complete SCI cases, were analyzed in this study. Quantitative real-time PCR was used to measure the expression of miR-301a-3p. Receiver operating characteristic (ROC) was used to evaluate the diagnostic accuracy of serum miR-301a-3p in SCI. LPS-treated SH-SY5Y cells were used to mimic SCI inflammatory injury. The levels of IL-1ß, IL-6, TNF-α were detected using enzyme-linked immunosorbent assay. RESULTS: Expression of serum miR-301a-3p was significantly higher in both incomplete and complete SCI patients than that in neurologically normal controls, and had a significant ability to distinguish SCI patients from controls. Additionally, complete SCI cases had markedly increased miR-301a-3p compared to incomplete cases, and the two groups of patients could be distinguished based on serum deregulated miR-301a-3p. In the SCI cell model, miR-301a-3p overexpression led to decreased cell viability. The inflammatory responses of the cell model were enhanced by miR-301a-3p, which was consistent with the findings in SCI patients that serum miR-301a-3p was positively correlated with pro-inflammatory cytokines. CONCLUSION: The expression of miR-301a-3p is increased in SCI patients, and serves as a candidate biomarker for SCI diagnosis. MiR-301a-3p may be involved in SCI progression by affecting neuronal viability and inflammation.

Circ_0001103 alleviates IL-1ß-induced chondrocyte cell injuries by upregulating SIRT1 via targeting miR-375.

BACKGROUND: Osteoarthritis (OA) is a common inflammatory disease characterized by articular cartilage degeneration and injury. Circular RNAs (circRNAs) are widely involved in the development of human diseases, including OA. The objective of this study was to investigate the function and functional mechanism of circ_0001103 in OA. METHODS: Cell model of OA was established by treating chondrocytes with interleukin-1ß (IL-1ß). The expression of circ_0001103, miR-375 and sirtuin 1 (SIRT1) mRNA was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined using flow cytometry assay. The expression levels of inflammatory factors were quantified by qRT-PCR. The expression of extracellular matrix (ECM) metabolism-related markers, including Collagen Type II Alpha 1 Chain (COL2A1) and A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), was detected by western blot. Predicted target relationship between miR-375 and circ_0001103 or SIRT1 by the bioinformatics tools was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0001103 was downregulated in OA tissues and IL-1ß-induced chondrocytes. Overexpression of circ_0001103 attenuated IL-1ß-induced chondrocyte apoptosis, inflammatory responses and ECM degradation. MiR-375 was targeted by circ_0001103, and miR-375 could bind to SIRT1. Circ_0001103 overexpression increased the expression of SIRT1 by suppressing miR-375. Rescue experiments suggested that miR-375 restoration reversed the effects of circ_0001103 overexpression, and SIRT1 knockdown overturned the effects of miR-375 inhibition. CONCLUSION: Circ_0001103 governed the miR-375/SIRT1 axis to ameliorate IL-1ß-induced chondrocyte injuries, implying that circ_0001103 was a promising biomarker in OA pathogenesis.