Low-energy red light-emitting diode irradiation enhances osteogenic differentiation of periodontal ligament stem cells by regulating miR-146a-5p.

AIMS: The study aimed to investigate the role of miR-146a-5p in osteogenesis of hPDLSCs irradiated with low-energy red LEDs. METHODS: After irradiation with 5 J/cm2 red LED, miR-146a-5p expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR), and osteogenic markers expression was determined by RT-qPCR and Western blotting. Alkaline phosphatase (ALP) activity was assessed by ALP staining, and mineralization was assessed by Alizarin Red staining, respectively. Lentiviral vectors were designed to regulate miR-146a-5p expression. Dual-luciferase reporter assay was performed to confirm the targeted relationship between miR-146a-5p and MAPK1. Short hairpin RNA (shRNA) was used to regulate MAPK1 expression. RESULTS: RT-qPCR and western blotting revealed that 5 J/cm2 irradiation elevated the levels of the osteogenic markers osterix (OSX) and bone sialoprotein (BSP) in hPDLSCs. miR-146a-5p is downregulated in hPDLSCs under the low-energy red LED light irradiation. miR-146a-5p underexpression markedly promoted the osteogenic potential of hPDLSCs. miR-146a-5p targeted MAPK1. 5 J/cm2 red LED irradiation rescued the inhibitory effects of upregulated miR-146a-5p on osteogenic differentiation, and the positive influence of red LED irradiation could be reversed by downregulated MAPK1. CONCLUSION: These findings confirm that miR-146a-5p is involved in the effect of LED irradiation on the osteogenic differentiation of hPDLSCs by targeting MAPK1. Red LED irradiation may be a potential clinical adjunct therapy for periodontal regeneration.

Differential expression of circRNAs during osteogenic/odontogenic differentiation of stem cells from apical papilla promoted by blue light-emitting diode.

BACKGROUND: Circular RNA (circRNA) is a key player in regulating the multidirectional differentiation of stem cells. Previous research by our group found that the blue light-emitting diode (LED) had a promoting effect on the osteogenic/odontogenic differentiation of human stem cells from apical papilla (SCAPs). This research aimed to investigate the differential expression of circRNAs during the osteogenic/odontogenic differentiation of SCAPs regulated by blue LED. MATERIALS AND METHODS: SCAPs were divided into the irradiation group (4 J/cm2) and the control group (0 J/cm2), and cultivated in an osteogenic/odontogenic environment. The differentially expressed circRNAs during osteogenic/odontogenic differentiation of SCAPs promoted by blue LED were detected by high-throughput sequencing, and preliminarily verified by qRT-PCR. Functional prediction of these circRNAs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the circRNA-miRNA-mRNA networks were also constructed. RESULTS: It showed 301 circRNAs were differentially expressed. GO and KEGG analyses suggested that these circRNAs were associated with some signaling pathways related to osteogenic/odontogenic differentiation. And the circRNA-miRNA-mRNA networks were also successfully constructed. CONCLUSION: CircRNAs were involved in the osteogenic/odontogenic differentiation of SCAPs promoted by blue LED. In this biological process, circRNA-miRNA-mRNA networks served an important purpose, and circRNAs regulated this process through certain signaling pathways.

MicroRNA-671-5p regulates the inflammatory response of periodontal ligament stem cells via the DUSP8/p38 MAPK pathway.

BACKGROUND: MicroRNAs are differentially expressed in periodontitis tissues. They are involved in cellular responses to inflammation and can be used as markers for diagnosing periodontitis. Microarray analysis showed that the expression level of microRNA-671-5p in periodontal tissues of patients with periodontitis was increased. In this study, we investigated the mechanism of action of microRNA-671-5p in human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions. METHODS AND RESULTS: HPDLSCs were treated with lipopolysaccharide (LPS) to establish an inflammation model. The cell survival rate was determined using the cell counting kit-8 (CCK8). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the expression of microRNA-671-5p and dual-specificity phosphatase (DUSP) 8 proteins, respectively, Interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were detected using qRT-PCR and Enzyme-linked immunosorbent assay (ELISA). A dual-luciferase reporter system was employed to determine the relationship between micoRNA-671-5p and DUSP8 expression. Activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway was confirmed using western blot analysis. Following the treatment of hPDLSCs with LPS, the expression levels of microRNA-671-5p in hPDLSCs were increased, cell viability decreased, and the expression of inflammatory factors displayed an increasing trend. MicroRNA-671-5p targets and binds to DUSP8. Silencing microRNA-671-5p or overexpressing DUSP8 can improve cell survival rate and reduce inflammatory responses. When DUSP8 was overexpressed, the expression of p-p38 was reduced. CONCLUSIONS: microRNA-671-5p targets DUSP8/p38 MAPK pathway to regulate LPS-induced proliferation and inflammation in hPDLSCs.

Comparison of Flaps From Different Sites for Repairing Postoperative Soft Tissue Defects Regarding the Quality of Life in Patients With Oral Cancer: A Systematic Review.

This study aims to compare flaps at different sites in treating soft tissue defects after oral cancer surgery and improving patients' quality of life (QoL). Databases were searched until September 2023. The extracted data included the scores of chewing, swallowing, speech, mood, and appearance based on the University of Washington QoL questionnaire, version 4. Two types of free flaps and 2 types of pedicled tissue flaps were included. The free flaps were the forearm free flap (FFF) and anterolateral thigh flap, and the pedicled tissue flaps were the submental artery island flap and pectoralis major myocutaneous flap (PMMF). Compared with FFF, there was no significant difference in the scores of chewing, swallowing, speech, and mood among anterolateral thigh, submental artery island flap, and PMMF, and PMMF generally had a higher score than FFF only in terms of appearance, with statistical significance. There is no significant difference in chewing, swallowing, speech, and mood between flaps from different sites in repairing postoperative soft tissue defects of oral cancer. Therefore, the widely used FFF may be the preferred choice considering the QoL of patients after oral cancer surgery.

The implication of blue light-emitting diode on mesenchymal stem cells: a systematic review.

The application of blue light (400-480 nm) in photobiotherapy remains controversial. This systematic review aimed to collect and analyze the biological effects of blue light-emitting diode (LED) on mesenchymal stem cells (MSCs). Inclusion and exclusion criteria were formulated, and relevant English articles from January 1982 to September 2022 were searched in PubMed, Scopus, and Web of Science. Nine articles with a medium (n = 4) to low (n = 5) risk of bias were included. Most of the MSCs reported were derived from human tissue; only one article used MSCs derived from mouse. The wavelength of the LED used was in the 400-480 nm range, and the irradiation modes were continuous (n = 8) and pulse waves (n = 1). A chiral polarizer was used in one such study in which the irradiance was 14 mW/cm2 and the irradiation time was 24 h. The energy densities used in other studies were between 0.378 and 72 J/cm2, and the irradiation times were between 10 and 3600 s. Blue LED light can inhibit proliferation and promote differentiation of MSCs in an appropriate energy density range, which may be related to the activation of transient receptor potential vanilloid 1 (TRPV1). Additionally, polarized light may reduce the toxic effects of blue light on MSCs. However, the heterogeneity of the design schemes and LED parameters, as well as the small number of studies, limited the conclusiveness of the review. Therefore, further studies are needed to determine the optimal irradiation strategy for promoting MSC function.

Myeloid-derived suppressor cells: key immunosuppressive regulators and therapeutic targets in hematological malignancies.

The immunosuppressive tumor microenvironment (TME) supports the development of tumors and limits tumor immunotherapy, including hematological malignancies. Hematological malignancies remain a major public health issue with high morbidity and mortality worldwide. As an important component of immunosuppressive regulators, the phenotypic characteristics and prognostic value of myeloid-derived suppressor cells (MDSCs) have received much attention. A variety of MDSC-targeting therapeutic approaches have produced encouraging outcomes. However, the use of various MDSC-targeted treatment strategies in hematologic malignancies is still difficult due to the heterogeneity of hematologic malignancies and the complexity of the immune system. In this review, we summarize the biological functions of MDSCs and further provide a summary of the phenotypes and suppressive mechanisms of MDSC populations expanded in various types of hematological malignancy contexts. Moreover, we discussed the clinical correlation between MDSCs and the diagnosis of malignant hematological disease, as well as the drugs targeting MDSCs, and focused on summarizing the therapeutic strategies in combination with other immunotherapies, such as various immune checkpoint inhibitors (ICIs), that are under active investigation. We highlight the new direction of targeting MDSCs to improve the therapeutic efficacy of tumors.

Phenotypes of peripheral CD4+ T helper cell subsets in pregnant women with HBeAg-negative chronic asymptomatic HBV carriers.

Background: Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide, and mother-to-child transmission is the key mode of HBV infection. CD4+ T helper (Th) cells play a critical role in the immune microenvironment of specific maternal tolerance to the foetus during pregnancy. However, the roles of Th cell subsets in pregnant women (PW) with chronic asymptomatic HBV carriers (ASCs) remain completely unclear. Here, we aimed to characterize CD4+ T-cell immunity in PW with hepatitis Be antigen (HBeAg)-negative chronic ASCs. Methods: Human peripheral blood mononuclear cells (PBMCs) from PW without HBV infection or with chronic ASCs and healthy controls (HC) were isolated, and CD4+ Th cell subsets were detected by flow cytometry in addition to serum cytokines. Serological HBV markers, liver function and hormone levels of these individuals were also tested. Results: The frequencies of circulating T follicular helper (Tfh) type 2 (Tfh2) cells were significantly evaluated, but Tfh1 cell frequencies were notably decreased in PW compared to HC. Moreover, the frequencies of Th22 cells were only notably increased in PW with chronic ASCs in comparison with PW. Additionally, increased levels of serum IL-4 were positively correlated with Tfh2 cell frequencies in healthy PW. Interestingly, serum P4 levels were positively associated with the frequencies of circulating Tfh2 or Th2 cells but were negatively related to the frequencies of circulating Tfh17 or Th17 cells in healthy PW. Although there were some changes in the other CD4+ Th cell frequencies and cytokine levels or other references, significant differences were not found among HC, healthy PW, PW with HBeAg-negative chronic ASCs. Conclusion: CD4+ Th cell subsets played a critical role in the immune microenvironment of PW, and these findings provided potential evidence for why PW with chronic ASCs did not receive antenatal antiviral prophylaxis.

mTOR signaling: A pivotal player in Treg cell dysfunction in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by multiorgan involvement and marked variability in clinical presentation. SLE pathogenesis includes regulatory T cell dysfunction and antinuclear antibody production. Mammalian target of rapamycin (mTOR), a serine/threonine kinase in the phosphoinositide 3-kinase (PI3K)-related kinase family, is a therapeutic target for autoimmune diseases such as SLE. Rapamycin, an inhibitor of the mTOR signaling pathway, is a macrolide antibiotic with potent immunosuppressive, antiproliferative and antifibrotic effects. Recently, an increasing number of studies have investigated the role of mTOR in regulatory T (Treg) cells and its impact on SLE pathogenesis. This review aims to systematically summarize the role of the mTOR signaling pathway in SLE pathogenesis, Treg cell dysfunction and SLE treatment.

NIR-I Dye-Based Probe: A New Window for Bimodal Tumor Theranostics.

Near-infrared (NIR, 650-1700 nm) bioimaging has emerged as a powerful strategy in tumor diagnosis. In particular, NIR-I fluorescence imaging (650-950 nm) has drawn more attention, benefiting from the high quantum yield and good biocompatibility. Since their biomedical applications are slightly limited by their relatively low penetration depth, NIR-I fluorescence imaging probes have been under extensive development in recent years. This review summarizes the particular application of the NIR-I fluorescent dye-contained bimodal probes, with emphasis on related nanoprobes. These probes have enabled us to overcome the drawbacks of individual imaging modalities as well as achieve synergistic imaging. Meanwhile, the application of these NIR-I fluorescence-based bimodal probes for cancer theranostics is highlighted.

Restoring MLL reactivates latent tumor suppression-mediated vulnerability to proteasome inhibitors.

MLL undergoes multiple distinct chromosomal translocations to yield aggressive leukemia with dismal outcomes. Besides their well-established role in leukemogenesis, MLL fusions also possess latent tumor-suppressive activity, which can be exploited as effective cancer treatment strategies using pharmacological means such as proteasome inhibitors (PIs). Here, using MLL-rearranged xenografts and MLL leukemic cells as models, we show that wild-type MLL is indispensable for the latent tumor-suppressive activity of MLL fusions. MLL dysfunction, shown as loss of the chromatin accumulation and subsequent degradation of MLL, compromises the latent tumor suppression of MLL-AF4 and is instrumental for the acquired PI resistance. Mechanistically, MLL dysfunction is caused by chronic PI treatment-induced epigenetic reprogramming through the H2Bub-ASH2L-MLL axis and can be specifically restored by histone deacetylase (HDAC) inhibitors, which induce histone acetylation and recruits MLL on chromatin to promote cell cycle gene expression. Our findings not only demonstrate the mechanism underlying the inevitable acquisition of PI resistance in MLL leukemic cells, but also illustrate that preventing the emergence of PI-resistant cells constitutes a novel rationale for combination therapy with PIs and HDAC inhibitors in MLL leukemias.

SENP2 exerts an anti­tumor effect on chronic lymphocytic leukemia cells through the inhibition of the Notch and NF­κB signaling pathways.

Chronic lymphocytic leukemia (CLL) is one of the most often diagnosed hematological malignant tumors in the Western world and a type of inert B­cell lymphoma that commonly attacks the elderly. Small ubiquitin related modifier (SUMO)­specific protease 2 (SENP2) can act as a suppressor in various types of cancer by regulating the stability of ß­catenin to affect the Notch signaling pathway; however, it has a low expression level in CLL cells. In this study, we firstly used western blot analysis and RT­qPCR to detect the protein and mRNA expression levels of SENP2 in the peripheral blood of patients with CLL and healthy volunteers. Secondly, we overexpressed or knocked down the expression of SENP2 in CLL cells and then determined the cell invasive and chemotactic ability in a Transwell assay and chemotaxis assay. We examined the sensitivity of the cells to cytarabine and dexamethasone via a CCK­8 assay and determined the cell apoptotic condition and the expression of the Notch signaling pathway using flow cytometry and western blot analysis. The results demonstrated that the patients with CLL had relatively low expression levels of SENP2. The overexpression of SENP2 in the CLL cells decreased their invasive and proliferative ability, as well as their chemotactic response and enhanced their sensitivity to cytarabine and dexamethasone, while it promoted cell apoptosis. The silencing of SENP2 in the CLL cells generally produced the opposite results. We thus hypothesized that the overexpression of SENP2 downregulated ß­catenin expression, thus inhibiting the Notch signaling pathway in CLL cells. Moreover, the nuclear factor (NF)­κB signaling pathway was also regulated by the overexpression of SENP2. On the whole, the findings of this study indicate tha SENP2 can act as a tumor suppressor in CLL cells, and may thus prove to be a novel target for CLL treatment in clinical practice.