Hippo-PKCζ-NFκB signaling axis: A druggable modulator of chondrocyte responses to mechanical stress.

Recent studies have implicated a crucial role of Hippo signaling in cell fate determination by biomechanical signals. Here we show that mechanical loading triggers the activation of a Hippo-PKCζ-NFκB pathway in chondrocytes, resulting in the expression of NFκB target genes associated with inflammation and matrix degradation. Mechanistically, mechanical loading activates an atypical PKC, PKCζ, which phosphorylates NFκB p65 at Serine 536, stimulating its transcriptional activation. This mechanosensitive activation of PKCζ and NFκB p65 is impeded in cells with gene deletion or chemical inhibition of Hippo core kinases LATS1/2, signifying an essential role of Hippo signaling in this mechanotransduction. A PKC inhibitor AEB-071 or PKCζ knockdown prevents p65 Serine 536 phosphorylation. Our study uncovers that the interplay of the Hippo signaling, PKCζ, and NFκB in response to mechanical loading serves as a therapeutic target for knee osteoarthritis and other conditions resulting from mechanical overloading or Hippo signaling deficiencies.

Interplay of RAP2 GTPase and the cytoskeleton in Hippo pathway regulation.

The Hippo signaling is instrumental in regulating organ size, regeneration, and carcinogenesis. The cytoskeleton emerges as a primary Hippo signaling modulator. Its structural alterations in response to environmental and intrinsic stimuli control Hippo signaling pathway activity. However, the precise mechanisms underlying the cytoskeleton regulation of Hippo signaling are not fully understood. RAP2 GTPase is known to mediate the mechanoresponses of Hippo signaling via activating the core Hippo kinases LATS1/2 through MAP4Ks and MST1/2. Here we show the pivotal role of the reciprocal regulation between RAP2 GTPase and the cytoskeleton in Hippo signaling. RAP2 deletion undermines the responses of the Hippo pathway to external cues tied to RhoA GTPase inhibition and actin cytoskeleton remodeling, such as energy stress and serum deprivation. Notably, RhoA inhibitors and actin disruptors fail to activate LATS1/2 effectively in RAP2-deficient cells. RNA sequencing highlighted differential regulation of both actin and microtubule networks by RAP2 gene deletion. Consistently, Taxol, a microtubule-stabilizing agent, was less effective in activating LATS1/2 and inhibiting cell growth in RAP2 and MAP4K4/6/7 knockout cells. In summary, our findings position RAP2 as a central integrator of cytoskeletal signals for Hippo signaling, which offers new avenues for understanding Hippo regulation and therapeutic interventions in Hippo-impaired cancers.

CLSPN actives Wnt/ß-catenin signaling to facilitate glycolysis and cell proliferation in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is a common malignancy with a poor prognosis. This study aimed to determine the influence and underlying mechanisms of CLSPN on OSCC. METHODS: CLSPN expression was tested using quantitative real-time polymerase chain reaction, immunohistochemistry, and western blotting. Flow cytometry, cell counting kit, and colony formation assays were performed to determine OSCC cell apoptosis, viability, and proliferation, respectively. In OSCC cells, the extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose uptake, and lactate production were determined using the corresponding kits. Changes in the protein levels of HK2, PKM2, LDHA, Wnt3a, and ß-catenin were assessed using western blotting. RESULTS: CLSPN expression was increased in OSCC tissues. Overexpression of CLSPN in HSC-2 cells promoted cell proliferation, increased the levels of ECAR, glucose uptake, and lactate production, and increased the protein levels of HK2, PKM2, LDHA, Wnt3a, and ß-catenin, but inhibited OCR levels and apoptosis. The knockdown of CLSPN in CAL27 cells resulted in the opposite results. Moreover, the effects of CLSPN overexpression on glycolysis and OSCC cell proliferation were reversed by Wnt3a knockdown. In vivo, knockdown of CLSPN restrained tumor growth, glycolysis, and the activation of Wnt/ß-catenin signaling. CONCLUSION: CLSPN promoted glycolysis and OSCC cell proliferation, and reduced apoptosis, which was achieved by the activation of Wnt/ß-catenin signaling pathway.

The accuracy of Fiber-Optic Raman Spectroscopy in the detection and diagnosis of head and neck neoplasm in vivo: a systematic review and meta-analysis.

Purpose: The aim of this article was to review and collectively assess the published studies of fiber-optic Raman spectroscopy (RS) of the in vivo detection and diagnosis of head and neck carcinomas, and to derive a consensus average of the accuracy, sensitivity and specificity. Methods: The authors searched four databases, including Ovid-Medline, Ovid-Embase, Cochrane Library, and the China National Knowledge Infrastructure (CNKI), up to February 2023 for all published studies that assessed the diagnostic accuracy of fiber-optic RS in the in vivo detection of head and neck carcinomas. Nonqualifying studies were screened out in accordance with the specified exclusion criteria, and relevant information about the diagnostic performance of fiber-optic RS was excluded. Publication bias was estimated by Deeks' funnel plot asymmetry test. A random effects model was adopted to calculate the pooled sensitivity, specificity and diagnostic odds ratio (DOR). Additionally, the authors conducted a summary receiver operating characteristic (SROC) curve analysis and threshold analysis, reporting the area under the curve (AUC) to evaluate the overall performance of fiber-optic RS in vivo. Results: Ten studies (including 16 groups of data) were included in this article, and a total of 5365 in vivo Raman spectra (cancer = 1,746; normal = 3,619) were acquired from 877 patients. The pooled sensitivity and specificity of fiber-optic RS of head and neck carcinomas were 0.88 and 0.94, respectively. SROC curves were generated to estimate the overall diagnostic accuracy, and the AUC was 0.96 (95% CI [0.94-0.97]). No significant publication bias was found in this meta-analysis by Deeks' funnel plot asymmetry test. The heterogeneity of these studies was significant; the Q test values of the sensitivity and specificity were 106.23 (P = 0.00) and 64.21 (P = 0.00), respectively, and the I2 index of the sensitivity and specificity were 85.88 (95% CI [79.99-91.77]) and 76.64 (95% CI [65.45-87.83]), respectively. Conclusion: Fiber-optic RS was demonstrated to be a reliable technique for the in vivo detection of head and neck carcinoma with high accuracy. However, considering the high heterogeneity of these studies, more clinical studies are needed to reduce the heterogeneity, and further confirm the utility of fiber-optic Raman spectroscopy in vivo.

Research on the control strategy of DC microgrids with distributed energy storage.

As a supplement to large power grids, DC microgrids with new energy access are increasingly widely used. However, with the increasing proportion of new energy in DC microgrids, its output fluctuations directly affect the overall stability of the microgrids. Distributed energy storage can smooth the output fluctuation of distributed new energy. In this paper, an AC-DC hybrid micro-grid operation topology with distributed new energy and distributed energy storage system access is designed, and on this basis, a coordinated control strategy of a micro-grid system based on distributed energy storage is proposed. To maintain the voltage stability of the DC bus and make each station have the power-sharing ability, the AC/DC flexibly interconnected converter should adopt two control strategies. The power can flow bidirectional in the power scheduling and distribution of the energy storage station; At the same time, different power distribution schemes will generate different scheduling costs. To optimize the operation of energy storage power stations, an improved particle swarm optimization algorithm is adopted in this paper to optimize the scheduling task allocation scheme. The optimization objective is the lowest scheduling cost, to realize the optimal scheduling of energy storage power stations. In this paper, based on a Matlab/Simulink environment, a microgrid system based on an AC-DC hybrid bus is built. The simulation results verify the effectiveness of the proposed microgrid coordinated control strategy.

Interplay of RAP2 GTPase and the cytoskeleton in Hippo pathway regulation.

The Hippo signaling is instrumental in regulating organ size, regeneration, and carcinogenesis. The cytoskeleton emerges as a primary Hippo signaling modulator. Its structural alterations in response to environmental and intrinsic stimuli control Hippo kinase cascade activity. However, the precise mechanisms underlying the cytoskeleton regulation of Hippo signaling are not fully understood. RAP2 GTPase is known to mediate the mechanoresponses of Hippo signaling via activating the core Hippo kinases LATS1/2 through MAP4Ks and MST1/2. Here we show the pivotal role of the reciprocal regulation between RAP2 GTPase and the cytoskeleton in Hippo signaling. RAP2 deletion undermines the responses of the Hippo pathway to external cues tied to RhoA GTPase inhibition and actin cytoskeleton remodeling, such as energy stress and serum deprivation. Notably, RhoA inhibitors and actin disruptors fail to activate LATS1/2 effectively in RAP2-deficient cells. RNA sequencing highlighted differential regulation of both actin and microtubule networks by RAP2 gene deletion. Consistently, Taxol, a microtubule-stabilizing agent, was less effective in activating LATS1/2 and inhibiting cell growth in RAP2 and MAP4K4/6/7 knockout cells. In summary, our findings position RAP2 as a central integrator of cytoskeletal signals for Hippo signaling, which offers new avenues for understanding Hippo regulation and therapeutic interventions in Hippo-impaired cancers.

Hippo Signaling Modulates the Inflammatory Response of Chondrocytes to Mechanical Compressive Loading.

Knee osteoarthritis (KOA) is a degenerative disease resulting from mechanical overload, where direct physical impacts on chondrocytes play a crucial role in disease development by inducing inflammation and extracellular matrix degradation. However, the signaling cascades that sense these physical impacts and induce the pathogenic transcriptional programs of KOA remain to be defined, which hinders the identification of novel therapeutic approaches. Recent studies have implicated a crucial role of Hippo signaling in osteoarthritis. Since Hippo signaling senses mechanical cues, we aimed to determine its role in chondrocyte responses to mechanical overload. Here we show that mechanical loading induces the expression of inflammatory and matrix-degrading genes by activating the nuclear factor-kappaB (NFκB) pathway in a Hippo-dependent manner. Applying mechanical compressional force to 3-dimensional cultured chondrocytes activated NFκB and induced the expression of NFκB target genes for inflammation and matrix degradation (i.e., IL1ß and ADAMTS4). Interestingly, deleting the Hippo pathway effector YAP or activating YAP by deleting core Hippo kinases LATS1/2 blocked the NFκB pathway activation induced by mechanical loading. Consistently, treatment with a LATS1/2 kinase inhibitor abolished the upregulation of IL1ß and ADAMTS4 caused by mechanical loading. Mechanistically, mechanical loading activates Protein Kinase C (PKC), which activates NFκB p65 by phosphorylating its Serine 536. Furthermore, the mechano-activation of both PKC and NFκB p65 is blocked in LATS1/2 or YAP knockout cells, indicating that the Hippo pathway is required by this mechanoregulation. Additionally, the mechanical loading-induced phosphorylation of NFκB p65 at Ser536 is blocked by the LATS1/2 inhibitor Lats-In-1 or the PKC inhibitor AEB-071. Our study suggests that the interplay of the Hippo signaling and PKC controls NFκB-mediated inflammation and matrix degradation in response to mechanical loading. Chemical inhibitors targeting Hippo signaling or PKC can prevent the mechanoresponses of chondrocytes associated with inflammation and matrix degradation, providing a novel therapeutic strategy for KOA.

NUDT5-Determines the fate of head and neck squamous cell carcinoma cells under endoplasmic reticulum stress by catalyzing nuclear ATP production to promote DNA repair.

OBJECTIVES: NUDT5 is the only discovered enzyme that catalyses ATP production in cell nuclei. In this study, we investigate the character of NUDT5 in head and neck squamous cell carcinoma (HNSCC) cells under endoplasmic reticulum (ER) stress. METHODS: The formation of ER stress was confirmed in HNSCC cells using Real-time PCR and Western blot techniques. The expression of NUDT5 was modified by transfecting HNSCC cells with siRNA and plasmids, respectively. The effects of NUDT5 manipulation were assessed using various methods including cell counting kit-8 assay, western blotting, RNA sequencing, Immunofluorescence Microscopy analysis, cell cycle analysis and nucleic ATP measurement, and a xenograft mouse model. RESULTS: In this study, we found that the expression of NUDT5 proteins was upregulated under ER stress conditions in HNSCC cells. Knocking down NUDT5 under ER stress could hinder nuclear ATP generation and thus induce more DNA damage and apoptosis of HNSCC cells. Only the wild-type NUDT5 or ATP catalysis active mutant T45A-NUDT5, rather than the ATP catalysis null mutant T45D-NUDT5, could directly rescue nuclear ATP depletion caused by NUDT5 inhibition and protect HNSCC cells from DNA damage and cell apoptosis. Finally, in vivo studies showed that knocking down NUDT5 in ER-stressed conditions could significantly inhibit tumour growth. CONCLUSION: Our study demonstrated for the first time that NUDT5 guaranteed the integrity of DNA under ER stress-triggered DNA damage by catalysing nuclear ATP production. Our findings offer new insights into how the energy supply in cell nuclei fuels cancer cell survival in stressful microenvironment.

Global research trends in immunotherapy for head and neck neoplasms: A scientometric study.

In recent decades, the traditional treatment of head and neck neoplasms has reached a bottleneck with limited improvement in overall survival. Nevertheless, the emerging field of immunotherapy has shown promise. Literature on research into immunotherapy for head and neck neoplasms was retrieved from WoSCC. Citespace was used as a scientometric analysis tool for text mining and visualization of the scientific literature. This analysis included 1915 documents. Recently, the annual number of publications and citations has been growing rapidly. 'Oncology' was the most popular research area. The most dominant institution and country were the University of Pittsburgh and the USA. Ferris RL was not only the most prolific but also the most cited author, demonstrating a strong influence and reputation. Of the ten core journals identified in this field, Cancer Research ranked first. 'Regulatory T cell', 'PD-1' and 'biomarker' were regarded as current hotspots, while 'recurrent' and 'nivolumab' were considered as trending keywords. The most cited reference was Ferris RL (2016). Notably, the front trends and future directions in the field may lie in the clinical practice of combination therapy of immunotherapy plus other therapies, the mechanism of impaired immune surveillance, and the improvement in resistance to immunotherapeutic agents. It is firmly believed that the present scientometric analysis has provided both a macroscopic and microscopic overview of research into immunotherapy for head and neck neoplasms, which will assist researchers and oncologists to better understand this discipline and thus promote further development and policies in this field.

Gambogenic acid alleviates kidney fibrosis via epigenetic inhibition of EZH2 to regulate Smad7-dependent mechanism.

BACKGROUND: Epigenetics regulating gene expression plays important role in kidney fibrosis. Natural products originating from diverse sources including plants and microorganisms are capable to influence epigenetic modifications. Gambogenic acid (GNA) is a caged xanthone extracted from gamboge resin, exudation of Garcinia hanburyi Hook.f., and the effect of GNA on kidney fibrosis with its underlying mechanism on epigenetics remains unknown. PURPOSE: This study aimed to explore the role of GNA against kidney fibrogenesis by histone methylation mediating gene expression. METHODS: Two experimental mice of unilateral ureteral obstruction (UUO) and folic acid (FA) were given two dosages of GNA (3 and 6 mg/kg/d). TGF-ß1 was used to stimulate mouse tubular epithelial (TCMK-1) cells and siRNAs were transfected to verify the underlying mechanisms of GNA. Histological changes were evaluated by HE, MASSON stainings, immunohistochemistry and immunofluorescence. Western blot and qPCR were used to measure protein/gene transcription levels. RESULTS: GNA dose-dependently alleviated UUO-induced kidney fibrosis and FA-induced kidney early fibrosis, indicated by the pathology and fibrotic factor changes (α-SMA, collagen I, collagen VI, and fibronectin). Mechanically, GNA reduced enhancer of zeste homolog 2 (EZH2) and H3K27me3, promoted Smad7 transcription, and inhibited TGF-ß/Smad3 fibrotic signaling in injured kidneys. Moreover, with TGF-ß1-induced EZH2 increasing, GNA suppressed α-SMA, fibronectin and collagen levels in tubular epithelial TCMK-1 cells. Although partially decreasing EZH2, GNA did not influence fibrotic signaling in Smad7 siRNA-transfected TCMK-1 cells. CONCLUSION: Epigenetic inhibition of EZH2 by GNA ameliorated kidney fibrogenesis via regulating Smad7-meidated TGF-ß/Smad3 signaling.

Trends and Hotspots in Nanoparticles for the Targeted Delivery of Nucleic Acids: A Ten-Year Bibliometric Study.

Nanoparticles for the gene therapy field have seen remarkable progress over the last 10 years; however, low delivery efficiency and other reasons impede the clinical translation of nanocarriers. Therefore, a summary of hotspots and trends in this field is needed to promote further research development. In this research, from 2011 to 2021, 1,221 full records and cited references of Web of Science-indexed manuscripts regarding nanoparticle-targeted delivery systems have been analyzed by CiteSpace, VOSviewer, and MapEquation. In these software, keywords co-occurrence networks, alluvial diagram, co-citation networks, and structural variation analysis were carried out to emphasize the scientific community's focus on nanomedicine of targeted delivering of nucleic acids. Keywords such as transfection efficiency, tumor cell, membrane antigen, and siRNA delivery were highlighted in the density map from VOSviewer. In addition, an alluvial flow diagram was constructed to detect changes in concepts. In the co-citation network, cluster 1 (exosomes) and cluster 17 (genome editing) were new research fields, and the efforts in modifying nanoparticles were revealed in the structural variation analysis. Aptamer and SELEX (systematic evolution of ligands by exponential enrichment) represented a helpful system in targeted delivery. These results indicated that the transfection efficiency of nanocarriers required continuous improvements. With the approval of several nucleic acid drugs, a new content of nanoparticle carriers is to introduce gene-editing technology, especially CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9). In addition, exosomes have great potential as targeted nanoparticles. By mapping the knowledge domains of nanomedicine in targeted delivering of nucleic acids, this study analyzed the intellectual structure of this domain in the recent 10 years, highlighting classical modifications on nanoparticles and estimating future trends for researchers and decision-makers interested in this field.

Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies.

Aging is a multifaceted and complicated process, manifested by a decline of normal physiological functions across tissues and organs, leading to overt frailty, mortality, and chronic diseases, such as skeletal, cardiovascular, and cognitive disorders, necessitating the development of practical therapeutic approaches. Stem cell aging is one of the leading theories of organismal aging. For decades, mesenchymal stem/stromal cells (MSCs) have been regarded as a viable and ideal source for stem cell-based therapy in anti-aging treatment due to their outstanding clinical characteristics, including easy accessibility, simplicity of isolation, self-renewal and proliferation ability, multilineage differentiation potentials, and immunomodulatory effects. Nonetheless, as evidenced in numerous studies, MSCs undergo functional deterioration and gradually lose stemness with systematic age in vivo or extended culture in vitro, limiting their therapeutic applications. Even though our understanding of the processes behind MSC senescence remains unclear, significant progress has been achieved in elucidating the aspects of the age-related MSC phenotypic changes and possible mechanisms driving MSC senescence. In this review, we aim to summarize the current knowledge of the morphological, biological, and stem-cell marker alterations of aging MSCs, the cellular and molecular mechanisms that underlie MSC senescence, the recent progress made regarding the innovative techniques to rejuvenate senescent MSCs and combat aging, with a particular focus on the interplay between aging MSCs and their niche as well as clinical translational relevance. Also, we provide some promising and novel directions for future research concerning MSC senescence.

Emerging trends in photodynamic therapy for head and neck cancer: A 10-year bibliometric analysis based on CiteSpace.

BACKGROUND: Head and neck cancer (HNC) was the seventh most common cancer worldwide. Photodynamic therapy (PDT) is a clinically approved, minimally invasive treatment, which was shown to be effective in the treatment of head and neck cancer and potentially malignant disorders. We used a bibliometric analysis to analyze the publications of radiomics in oncology to clearly illustrate the current situation and future trends and encourage more researchers to participate in radiomics research in oncology. METHODS: Publications for Photodynamic therapy in for head and neck cancer and potentially malignant disorders were downloaded from the Web of Science Core Collection (WoSCC). CiteSpace was used for a bibliometric analysis of countries, institutions, journals, authors, keywords, and references pertaining to this field. The state of research and areas of focus were analyzed through burst detection. RESULTS: A total of 1002 studies were used for analysis on CiteSpace. The USA is in first place by number of publications. Hopper C, was the most prolific author, and the author with the most citations was Chen XY. Among the journals and the co-cited journals, "Photodiagnosis and Photodynamic Therapy" was the first. "Nanoparticle" showed the highest burst strength level and materials research is major area of focus in this field. CONCLUSIONS: This bibliometric analysis of photodynamic therapy in head and neck cancer, provides a visual analysis of publications in this field. The conclusion of the current research in this field was that it focused on the research of photosensitizers, particularly nanomaterials and targeted therapies.

Unraveling the binding microprocess of individual Streptococcus mutans cells via sucrose-dependent adhesion based on surface plasmon resonance imaging.

The initial microprocess of a major cariogenic bacterium Streptococcus mutans forming biofilm at a single-cell level via sucrose-dependent adhesion has not been observed because the cells' high moisture content caused measurement challenges. To develop a high-sensitivity biosensor chip and a real-time, label-free method to observe bioactive molecule interactions with single cells from oral biofilms. We made the chips of immobilized bacteria by micronano-processing. A surface plasmon resonance imaging (SPRI) system was used to detect and record the association and dissociation microprocess of S. mutans with sucrose/dextran solutions of various concentrations, and the calculus model was adopted to treat the data. At the location of S. mutans, a unique 'comet-tail' SPRI signal was observed. The binding patterns of S. mutans differed between individual cells exposed to the same solution as well as between sucrose and dextran. The different cells exhibited different affinities with dissociation constants for sucrose being 5.697 × 10-3 to 3.689 M and for dextran 1.235 × 10-3 to 1.282 M, indicating cell-to-cell heterogeneity. Our SPRI detection method is effective in investigating microbial binding, initial biofilm formation, and oral microecology. It offers new possibilities for studying oral microorganism characteristics and development of oral diseases.

Semaphorin 7A Accelerates the Inflammatory Osteolysis of Periapical Lesions.

INTRODUCTION: Semaphorin 7A (SEMA7A), the only class VII semaphorin member, has been considered as a potent immunomodulatory regulator whose function in periapical lesions remains unclear. In our previous study, we found that SEMA7A was up-regulated in human periapical periodontitis and might be involved in the immune response and tissue destruction of periapical lesions. In this research, we aimed to further explore the specifical regulatory role of SEMA7A as well as its regulatory mechanisms in the inflammatory progression of periapical lesions. METHODS: Human periodontal ligament cells (hPDLCs) were collected from intact, caries-free, and healthy third molars and stimulated with recombinant human/mouse SEMA7A (rSEMA7A). Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, and enzyme-linked immunosorbent assay were used to detect the messenger RNA and protein levels of inflammatory cytokines and matrix metalloproteinases (MMPs) in hPDLCs. Twenty C57BL/6 mice were randomly divided into 4 groups: the healthy control group, pulp exposure group, pulp exposure and saline treatment group, and pulp exposure and rSEMA7A treatment group. Twenty microliters of sterile saline or 4 µg rSEMA7A were injected respectively into the buccal mucosa around the root apex at day 0, 7, and 14. Mandibular tissues were collected at day 21. Micro-computed tomographic and immunohistochemical staining were used to identify the bone destruction and inflammatory infiltration in periapical areas. Finally, an AKT inhibitor (LY294002) was used to pretreat hPDLCs before rSEMA7A stimulation to determine the role of AKT signaling activation in this process. RESULTS: After treatment with rSEMA7A, the messenger RNA and protein levels of interleukin (IL)-1ß, IL-18, cyclooxygenase-2, MMP-1, and MMP-3 were remarkably up-regulated in hPDLCs. For in vivo experiments, compared with the other 3 groups, the treatment of rSEMA7A aggravated the osteolysis of alveolar bone and promoted the infiltration of immune cells into the apex area, along with increased expression levels of IL-1ß, IL-18, MMP-1, and MMP-3. Furthermore, we found that the proinflammatory role of SEMA7A could be inhibited by the application of the AKT inhibitor (LY294002). CONCLUSIONS: SEMA7A likely aggravates the inflammatory reaction and bone destruction of existing periapical lesions. The proinflammatory role of SEMA7A in hPDLCs could partially be mediated through the AKT signaling transduction pathway.

Efficacy of probiotics in the management of halitosis: a systematic review and meta-analysis.

BACKGROUND: Halitosis is defined as a foul odour emitted from the oral cavity. Many interventions have been used to control halitosis from mouthwashes to chewing gums. Probiotics have been reported as an alternative method to alleviate halitosis. OBJECTIVE: The present study aimed to investigate the effect of probiotics on halitosis from a time perspective. DESIGN AND METHODS: This is a meta-analysis study performed in indexed databases up to February 2021. Randomised controlled trials that compared the effects of probiotics and placebo on primary outcomes (organoleptic (OLP) scores and volatile sulfur compound (VSC) levels) and secondary outcomes (tongue coating scores (TCS) and plaque index (PI)) were included. Data extraction and quality assessment were conducted independently by two reviewers. Publication bias and leave-one-out analyses were performed. RESULTS: The standardised mean difference (SMD) and 95% CI were calculated to synthesise data. The data were subgrouped and analysed in the short term (≤4 weeks) and long term (>4 weeks) based on the follow-up time. Seven articles were included in this meta-analysis. The primary outcomes, OLP scores (SMD=-0.58; 95% CI -0.87 to -0.30, p<0.0001) and VSC levels (SMD=-0.26; 95% CI -0.51 to -0.01, p=0.04), both decreased significantly in the probiotics group compared with the placebo group in the short term. However, a significant reduction was observed only in OLP scores (SMD=-0.45; 95% CI -0.85 to -0.04, p=0.03) in the long term. No significant differences were observed in secondary outcomes. There was no evidence of publication bias. The leave-one-out analysis confirmed that the pooled estimate was stable. CONCLUSIONS: According to the results of this work, it seems that probiotics (eg, Lactobacillus salivarius, Lactobacillus reuteri, Streptococcus salivarius and Weissella cibaria) may relieve halitosis in the short term (≤4 weeks). The results of the biased assessment, limited data and heterogeneity of the clinical trials included might reduce the reliability of the conclusions.

Oral cancer cells affect pancreatic ß-cell function through transmissible endoplasmic reticulum stress.

OBJECTIVES: In this study, we aimed to investigate whether oral cancer cells affect pancreatic ß-cells function through transmissible endoplasmic reticulum stress (TERS). METHODS: Tunicamycin (TM) was selected as the endoplasmic reticulum stress (ERS) inducer. The human oral cancer cell lines CAl-27 and SCC-25 were selected as the donor cells, and mouse insulinoma 6 (MIN6) cell lines were chosen as the recipient cells. Quantitative real-time polymerase chain reaction (qPCR) and Western blot (WB) analysis were used to detect ERS markers and insulin expression. The TdT-mediated dUTP nick-end labeling (TUNEL) method was applied to detect apoptosis levels. The clone formation method was utilized to detect cell proliferation capability. The secretory function of pancreatic ß-cells was detected with an enzyme linked immunosorbent assay (ELISA) kit and a bicinchoninic acid (BCA) kit. RESULTS: The MIN6 cells were subjected to TM stimulation. qPCR and WB analysis revealed that ERS markers were upregulated. This result implied that the MIN6 cells can induce ERS. The supernatant of oral cancer cells under ERS was added to the MIN6 cells. qPCR and WB analysis showed that the oral cancer cells that had been subjected to ERS could induce ERS in the MIN6 cells, that is, the phenomenon of TERS occurred. The TUNEL assay indicated that the apoptosis of the MIN6 cells increased under TERS. The clone formation assay demonstrated that the proliferation capability of the MIN6 cells decreased under TERS. qPCR and WB analysis revealed that under TERS, insulin synthesis by the MIN6 cells decreased and insulin synthesis was inhibited at the translation level. The ELISA and BCA kits demonstrated that insulin secretion by the MIN6 cells was reduced under TERS. CONCLUSIONS: Oral cancer cells can affect pancreatic ß-cells through TERS, resulting in increased apoptosis, decreased viability, and reduced insulin secretion and synthesis capability.

Near-infrared light-responsive hybrid hydrogels for the synergistic chemo-photothermal therapy of oral cancer.

Light-stimulus-responsive therapies have been recognized as a promising strategy for the efficient and safe treatment of oral squamous cell carcinoma (OSCC). Hydrogels have emerged as a promising multifunctional platform combining localized drug delivery and sustained drug release with multimodal properties for combined OSCC therapy. However, inaccurate drug release and limited light-absorption efficiency have hindered their on-demand chemo-photothermal applications. To tackle these problems, an injectable and near-infrared (NIR) light-responsive hybrid system was developed by incorporating light-responsive mesoporous silica nanoparticles (MSNs) as doxorubicin (DOX) carriers into the IR820/methylcellulose hydrogel networks for chemophotothermal therapy. Under NIR radiation, the incorporated IR820, a new green cyanine dye, was excited to induce photothermal effects against tumor cells. Meanwhile, MSNs achieved self-degradation-controlled DOX release via the cleavage of diselenide bonds induced by reactive oxygen species. Through the combination of chemotherapy and phototherapy, a long-lasting synergistic anti-tumor effect was achieved in vitro and in vivo with less toxicity. These findings demonstrate the potential of light-responsive hydrogels as a multifunctional platform for accurate synergistic chemophotothermal treatment of OSCC.

Radiomics in Oncology: A 10-Year Bibliometric Analysis.

OBJECTIVES: To date, radiomics has been applied in oncology for over a decade and has shown great progress. We used a bibliometric analysis to analyze the publications of radiomics in oncology to clearly illustrate the current situation and future trends and encourage more researchers to participate in radiomics research in oncology. METHODS: Publications for radiomics in oncology were downloaded from the Web of Science Core Collection (WoSCC). WoSCC data were collected, and CiteSpace was used for a bibliometric analysis of countries, institutions, journals, authors, keywords, and references pertaining to this field. The state of research and areas of focus were analyzed through burst detection. RESULTS: A total of 7,199 pieces of literature concerning radiomics in oncology were analyzed on CiteSpace. The number of publications has undergone rapid growth and continues to increase. The USA and Chinese Academy of Sciences are found to be the most prolific country and institution, respectively. In terms of journals and co-cited journals, Scientific Reports is ranked highest with respect to the number of publications, and Radiology is ranked highest among co-cited journals. Moreover, Jie Tian has published the most publications, and Phillipe Lambin is the most cited author. A paper published by Gillies et al. presents the highest citation counts. Artificial intelligence (AI), segmentation methods, and the use of radiomics for classification and diagnosis in oncology are major areas of focus in this field. Test-retest statistics, including reproducibility and statistical methods of radiomics research, the relation between genomics and radiomics, and applications of radiomics to sarcoma and intensity-modulated radiotherapy, are frontier areas of this field. CONCLUSION: To our knowledge, this is the first study to provide an overview of the literature related to radiomics in oncology and may inspire researchers from multiple disciplines to engage in radiomics-related research.