No abstract

Hepatitis B virus (HBV) has been suspected to contribute to several autoimmune diseases, including Sjögren’s syndrome (SS), although the exact mechanism is unknown. The 2′–5′ oligoadenylate synthetase (OAS1) is one of the most important components of the immune system and has significant antiviral functions. We studied a polymorphism rs10774671 of OAS1 gene in Han Chinese descent. The minor allele G was significantly associated with a decreased risk for SS, anti-SSA-positive SS, and anti-SSA-positive SS complicated with HBV infection, which have not been seen in anti-SSA-negative SS and HBcAb-negative SS patients. Gene expression analysis showed that the risk-conferring A allele was correlated with lower expression of p46 and increased expression of p42, p48, and p44. A functional study of enzymatic activities revealed that the p42, p44, and p48 isoforms display a reduced capacity to inhibit HBV replication in HepG2 cells compared to the normal p46 isoform. Our data demonstrated that the functional variant, rs10774671, is associated with HBV infection and anti-SSA antibody-positive SS. The SAS variant switches the primary p46 isoform to three alternatives with decreased capacities to inhibit HBV replication. These data indicated that individuals harboring the risk allele might be susceptible to hepatitis B infection and SS development.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma and has a poor prognosis. However, its underlying mechanisms remain unclear. The present study aimed to evaluate the role of small proline-rich repeat protein 3 (SPRR3) in the proliferation, migration and invasion of ccRCC cells and to investigate its upstream and downstream regulatory mechanisms. Survival analysis was performed using the UALCAN website based on the The Cancer Genome Atlas database. Normal renal cell line HK-2 and ccRCC cell lines (786-O, CaKi-1 and UMRC-2) were used. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect mRNA and microRNA (miRNA) levels. Western blotting was used to detect protein levels. Cell Counting Kit-8 and colony formation assays, a wound healing assay and a Transwell invasion assay were used to assess the proliferation, migration and invasion of ccRCC cells, respectively. Transfection of overexpression plasmids and small interfering RNAs were used to upregulate and knockdown SPRR3 expression, respectively. Transfection of miRNA-mimics was used to overexpress miR-338-3p. A luciferase reporter gene assay was used to verify the predicted binding relationship between SPRR3 mRNA and miR-338-3p. The results indicated the following: i) SPRR3 was a risk factor for the survival of patients with ccRCC, and was upregulated in ccRCC cell lines; ii) SPRR3 promoted the proliferation, migration and invasion of ccRCC cells; iii) SPRR3 regulated the tumor phenotypes of ccRCC cells via the PI3K/Akt pathway; iv) miR-338-3p directly targeted SPRR3 mRNA and negatively regulated SPRR3 expression; and v) miR-338-3p inhibited the PI3K/Akt pathway and the tumor phenotypes of ccRCC cells by downregulating SPRR3. In conclusion, SPRR3, as a novel target of miR-338-3p, regulated the proliferation, migration and invasion of ccRCC cells via the PI3K/Akt pathway; this finding not only enriches our understanding of the mechanism underlying ccRCC development, but also demonstrates a potential novel therapeutic target for this disease.

Hypertrophic scar (HS) is a kind of serious pathological scar with no currently effective treatment. HS fibroblasts (HSFs) are the main effector cells for HS formation. Ellagic acid (EA) exerts regulatory effects in some diseases, but its role in HS remains unclear. This study aimed to evaluate the effect of EA on the fibrotic phenotypes of HSFs and to further investigate the downstream signaling mechanism. The cell counting kit-8 (CCK-8) assay was used to perform cytotoxicity and proliferation assays. HSFs migration was assessed using wound healing and transwell assays. HSFs contraction was measured by a collagen lattice contraction assay and detection of α-smooth muscle actin (α-SMA) expression. The levels of mRNA and protein were determined by qPCR and western blotting, respectively. The results showed that EA inhibited the proliferation, migration, and contraction of HSFs and collagen expression in HSFs in a dose-dependent manner. Furthermore, EA not only suppressed the Smad2/3 pathway but also reversed TGF-β1-induced activation of the Smad2/3 pathway and up-regulation of the fibrotic cellular phenotypes in HSFs. These findings demonstrate that EA exerts anti-fibrotic effects on HSFs by blocking the TGF-β1/Smad2/3 pathway, which indicates that EA is a potential therapeutic candidate for treatment of HS.

No abstract

Colorectal cancer (CRC) is a common type of malignant digestive tract tumor with a high incidence rate worldwide. Currently, the clinical treatment of CRC predominantly include surgical resection, postoperative chemotherapy, and radiotherapy. However, these treatments contain severe limitations such as drug side effects, the risk of recurrence and drug resistance. Some natural compounds found in plants, fungi, marine animals, and bacteria have been shown to inhibit the occurrence and development of CRC. Although the explicit molecular mechanisms underlying the therapeutic effects of these compounds on CRC are not clear, classical signaling transduction pathways such as NF-kB and Wnt/β-catenin are extensively regulated. In this review, we have summarized the specific mechanisms regulating the inhibition and development of CRC by various types of natural compounds through nine signaling pathways, and explored the potential therapeutic values of these natural compounds in the clinical treatment of CRC.

BackgroundHyperuricemia is generally defined as the high level of serum uric acid and is well known as an important risk factor for the development of various medical disorders. However, the medicinal treatment of hyperuricemia is frequently associated with multiple side-effects.MethodsThe therapeutic effect of noni (Morinda citrifolia L.) fruit juice on hyperuricemia and the underlying molecular mechanisms were investigated in mouse model of hyperuricemia induced by potassium oxonate using biochemical and high-throughput RNA sequencing analyses.ResultsThe levels of serum uric acid (UA) and xanthine oxidase (XOD) in mice treated with noni fruit juice were significantly decreased, suggesting that the noni fruit juice could alleviate hyperuricemia by inhibiting the XOD activity and reducing the level of serum UA. The contents of both serum creatinine and blood urine nitrogen of the noni fruit juice group were significantly lower than those of the model group, suggesting that noni fruit juice promoted the excretion of UA without causing deleterious effect on the renal functions in mice. The differentially expressed microRNAs involved in the pathogenesis of hyperuricemia in mice were identified by RNA sequencing with their target genes further annotated based on both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases to explore the metabolic pathways and molecular mechanisms underlying the therapeutic effect on hyperuricemia by noni fruit juice.ConclusionOur study provided strong experimental evidence to support the further investigations of the potential application of noni fruit juice in the treatment of hyperuricemia.

Purpose: To evaluate the efficacy and safety of selective aneurysmal sac neck-targeted embolization in patients undergoing endovascular aneurysm repair (EVAR) with hostile neck anatomy. Materials and Methods: We enrolled 28 patients with hostile neck anatomy who underwent EVAR with a low-profile stent graft between October 2020 and June 2022. Before excluding the entire aneurysm during the procedure, a buddy wire was loaded prophylactically into the sac through the contralateral limb side. When type Ia endoleak persist despite adjunctive treatment, this preloaded wire could be utilized as an access to enable a catheter to reach the space between the stent graft and sac neck to perform coil embolization. In the absence of type Ia endoleak, the wire was simply retracted. The primary outcome of this study was freedom from sac expansion and endoleak-related reinterventions during the follow-up period; secondary outcomes included technical success, intraoperative and in-hospital postoperative complications. Results: Out of the 28 patients with hostile neck morphology, 11 of them (39.5%) who had type Ia endoleak received intra-procedure treatment with sac neck-targeted detachable coil embolization. The preloaded wire was removed from 17 patients (60.7%) who did not show type Ia endoleak. The coiling group had longer operating durations (81.27±11.61 vs. 70.71±7.17 minutes, P<0.01) and utilized more contrast than the non-coiling group (177.45±52.41 vs. 108.24±17.49 ml, p<0.01). In the entire cohort, technical success was 100% and there were no procedure-related complications. At a mean follow-up of 18.6±5.2 months (range 12-31), there was no sac expansion(19 sac regression, 67.86%; 9 stability, 32.14% ) and endoleak-related reintervention. Conclusions: Selective aneurysmal sac neck-targeted embolization for the treatment of type Ia endoleak in patients with hostile neck anatomy undergoing EVAR is safe and could reduce type Ia endoleak and prevent related sac expansion after EVAR.