The dual role of regulatory T cells in hepatitis B virus infection and related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths worldwide. Hepatitis B virus (HBV) infection is a major etiologic factor leading to HCC. While there have been significant advancements in controlling HBV replication, achieving a complete cure for HBV-related HCC (HBV-HCC) remains an intricate challenge. HBV persistence is attributed to a myriad of mechanisms, encompassing both innate and adaptive immune responses. Regulatory T cells (Tregs) are pivotal in upholding immune tolerance and modulating excessive immune activation. During HBV infection, Tregs mediate specific T cell suppression, thereby contributing to both persistent infection and the mitigation of liver inflammatory responses. Studies have demonstrated an augmented expression of circulating and intrahepatic Tregs in HBV-HCC, which correlates with impaired CD8+ T cell function. Consequently, Tregs play a dual role in the context of HBV infection and the progression of HBV-HCC. In this comprehensive review, we discuss pertinent studies concerning Tregs in HBV infection, HBV-related cirrhosis and HCC. Furthermore, we summarize Treg responses to antiviral therapy and provide Treg-targeted therapies specific to HBV and HCC.

MicroRNA-29a-3p prevents Schistosoma japonicum-induced liver fibrosis by targeting Roundabout homolog 1 in hepatic stellate cells.

BACKGROUND: Schistosomiasis is a serious but neglected parasitic disease in humans that may lead to liver fibrosis and death. Activated hepatic stellate cells (HSCs) are the principal effectors that promote the accumulation of extracellular matrix (ECM) proteins during hepatic fibrosis. Aberrant microRNA-29 expression is involved in the development of fibrotic diseases. However, less is known about the role of miR-29 in Schistosoma japonicum (S. japonicum)-induced hepatic fibrosis. METHODS: The levels of microRNA-29a-3p (miR-29a-3p) and Roundabout homolog 1 (Robo1) were examined in liver tissues during S. japonicum infection. The possible involvement of the miR-29a-3p-Robo1 signaling pathway was determined. We used MIR29A conditional knock-in mice and mice injected with an miR-29a-3p agomir to investigate the role of miR-29a-3p in schistosomiasis-induced hepatic fibrosis. The functional contributions of miR-29a-3p-Robo1 signaling in liver fibrosis and HSC activation were investigated using primary mouse HSCs and the human HSC cell line LX-2. RESULTS: MiR-29a-3p was downregulated in humans and mice with schistosome-induced fibrosis, and Robo1 was upregulated in liver tissues. The miR-29a-3p targeted Robo1 and negatively regulated its expression. Additionally, the expression level of miR-29a-3p in schistosomiasis patients was highly correlated with the portal vein and spleen thickness diameter, which represent the severity of fibrosis. Furthermore, we demonstrated that efficient and sustained elevation of miR-29a-3p reversed schistosome-induced hepatic fibrosis. Notably, we showed that miR-29a-3p targeted Robo1 in HSCs to prevent the activation of HSCs during infection. CONCLUSIONS: Our results provide experimental and clinical evidence that the miR-29a-3p-Robo1 signaling pathway in HSCs plays an important role in the development of hepatic fibrosis. Therefore, our study highlights the potential of miR-29a-3p as a therapeutic intervention for schistosomiasis and other fibrotic diseases.

Long-term trends in the burden of edentulism in China over three decades: A Joinpoint regression and age-period-cohort analysis based on the global burden of disease study 2019.

Background: To investigate secular trends in edentulism incidence, prevalence, and years lived with disability (YLDs) rates in Chinese men and women from 1990 to 2019. Methods: Data were obtained from the Global Burden of Disease Study 2019. The annual percentage change and average annual percentage change were calculated using Joinpoint regression analysis. The age-period-cohort (APC) analysis estimated the independent age, period, and cohort effects. Results: From 1990 to 2019, the crude incidence, prevalence, and YLDs of edentulism in the Chinese population increased year by year, while the age-standardized incidence, prevalence, and YLDs decreased, and the latter was higher in women than in men. The APC analysis showed that the age effect increased in men and women from age 20 to 74 and decreased thereafter. The risk of tooth loss increased with age. However, the relationship was not linear. The temporal effect showed a gradual increase; the risk of missing teeth gradually increased with the changing modern living environment. The cohort effect showed a single decreasing trend, with the early birth cohort having a higher risk of tooth loss than the later birth cohort population. The age, period, and cohort effects were consistent for both sexes. Conclusion: Although the standardized incidence, prevalence, and YLD rate and cohort effect of dentition loss in China are declining, they are still causing a severe burden to China due to the continued aging of the population and the rising period effect. Despite the decreasing trends of the standardized incidence and prevalence of dentition loss and the rate of YLDs, China should develop more effective oral disease prevention and control strategies to reduce the increasing burden of edentulism in the older adult, especially in older women.

Endothelin receptors promote schistosomiasis-induced hepatic fibrosis via splenic B cells.

Endothelin receptors (ETRs) are activated by vasoactive peptide endothelins and involved in the pathogenesis of hepatic fibrosis. However, less is known about the role of ETRs in Schistosoma (S.) japonicum-induced hepatic fibrosis. Here, we show that the expression of ETRs is markedly enhanced in the liver and spleen tissues of patients with schistosome-induced fibrosis, as well as in murine models. Additional analyses have indicated that the expression levels of ETRs in schistosomiasis patients are highly correlated with the portal vein and spleen thickness diameter, both of which represent the severity of fibrosis. Splenomegaly is a characteristic symptom of schistosome infection, and splenic abnormality may promote the progression of hepatic fibrosis. We further demonstrate that elevated levels of ETRs are predominantly expressed on splenic B cells in spleen tissues during infection. Importantly, using a well-studied model of human schistosomiasis, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells characterized by interleukin-10 (IL-10) secretion and regulatory T (Treg) cell-inducing capacity. Our study provides insights into the mechanisms by which ETRs regulate schistosomiasis hepatic fibrosis and highlights the potential of endothelin receptor antagonist as a therapeutic intervention for fibrotic diseases.

Long non-coding RNA LINC00473 acts as a microRNA-29a-3p sponge to promote hepatocellular carcinoma development by activating Robo1-dependent PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Long non-coding RNAs have suppressive or oncogenic effects in various types of cancers by serving as competing endogenous RNAs for specific microRNAs. In the present study, we aim to delineate the underlying mechanism by which the LINC00473/miR-29a-3p/Robo1 axis affects cell proliferation, migration, invasion, and metastasis in hepatocellular carcinoma (HCC). METHODS: The level of Robo1 was examined in HCC tissues and cells, along with its regulatory effects on proliferation, migration, and invasion of HCC cells. Afterwards, the possible involvement of the PI3K/AKT/mTOR signaling pathway was determined. Next, miR-29a-3p expression was overexpressed or inhibited to investigate its regulatory role on HCC cell activities. The interaction among miR-29a-3p, Robo1, and LINC00473 was further characterized. Finally, a xenograft tumor in nude mice was conducted to measure tumorigenesis and metastasis in vivo. RESULTS: miR-29a-3p was downregulated while Robo1 was upregulated in HCC tissues and cells. miR-29a-3p targeted Robo1 and negatively regulated its expression. In response to miR-29a-3p overexpression, Robo1 silencing or LINC00473 silencing, HCC cell proliferation, migration, invasion, tumor progression, and metastasis were impeded, which was involved with the inactivation of the PI3K/AKT/mTOR signaling pathway. Notably, LINC00473 could competitively bind to miR-29a-3p to upregulate Robo1 expression. CONCLUSION: LINC00473 might be involved in HCC progression by acting as a miR-29a-3p sponge to upregulate the expression of Robo1 that activates the PI3K/AKT/mTOR signaling pathway, which leads to enhanced cell proliferation, migration, invasion, tumor progression, and metastasis in HCC.

Comparison of vacuum-formed and Hawley retainers: a systematic review.

INTRODUCTION: Hawley retainers (HRs) and vacuum-formed retainers (VFRs) are the 2 most commonly used retainers in orthodontics. However, the basis for selection of an appropriate retainer is still a matter of debate among orthodontists. In this systematic review, we evaluated the differences between VFRs and HRs. METHODS: Electronic databases (PubMed, EMBASE, Cochrane Library, ISI Web of Science, LILACS, and Pro-Quest) were searched with no language restriction. The relevant orthodontic journals and reference lists were checked for all eligible studies. Two article reviewers independently screened the retrieved studies, extracted the data, and evaluated the quality of the primary studies. RESULTS: A total of 89 articles were retrieved in the initial search. However, only 7 articles met the inclusion criteria. Some evidence suggested that no difference exists to distinguish between the HRs and VFRs with respect to changes in intercanine and intermolar widths after orthodontic retention. In terms of occlusal contacts, cost effectiveness, patient satisfaction, and survival time, there was insufficient evidence to support the use of VFRs over HRs. CONCLUSIONS: Additional high-quality, randomized, controlled trials concerning these retainers are necessary to determine which retainer is better for orthodontic procedures.

In vitro assembly of R-phycoerythrin from marine red alga Polysiphonia urceolata.

Scanning tunneling microscope was used to investigate the in vitro assembly of R-phycoerythrin (R-PE) from the marine red alga Polysiphonia urceolata. The results showed that R-PE molecules assembled together by disc-to-disc while absorbing on HOPG surface, which just looked like the rods in the phycobilisomes. When the water-soluble R-PE was dissolved in 2% ethanol/water spreading solution, they could form monolayer film at the air/water interface. Similar disc-to-disc array of R-PE was constituted in the two-dimensional Langmuir-Blodgett film by the external force. It could be concluded that, apart from the key role of the linker polypeptides, the in vivo assembly of phycobiliproteins into phycobilisomes is also dependent on the endogenous properties of phycobiliprotein themselves.