Central post-stroke pain: advances in clinical and preclinical research.

Central poststroke pain (CPSP) is a medical complication that arises poststroke and significantly impacts the quality of life and social functioning of affected individuals. Despite ongoing research, the exact pathomechanisms of CPSP remain unclear, and practical treatments are still unavailable. Our review aims to systematically analyse current clinical and preclinical studies on CPSP, which is critical for identifying gaps in knowledge and guiding the development of effective therapies. The review will clarify the clinical characteristics, evaluation scales and contemporary therapeutic approaches for CPSP based on clinical investigations. It will particularly emphasise the CPSP model initiated by stroke, shedding light on its underlying mechanisms and evaluating treatments validated in preclinical studies. Furthermore, the review will not only highlight methodological limitations in animal trials but also offer specific recommendations to researchers to improve the quality of future investigations and guide the development of effective therapies. This review is expected to provide valuable insights into the current knowledge regarding CPSP and can serve as a guide for future research and clinical practice. The review will contribute to the scientific understanding of CPSP and help develop effective clinical interventions.

The role of metal ions in stroke: Current evidence and future perspectives.

Metal ions play a pivotal role in maintaining optimal brain function within the human body. Nevertheless, the accumulation of these ions can result in irregularities that lead to brain damage and dysfunction. Disruptions of metal ion homeostasis can result in various pathologies, including inflammation, redox dysregulation, and blood-brain barrier disruption. While research on metal ions has chiefly focused on neurodegenerative diseases, little attention has been given to their involvement in the onset and progression of stroke. Recent studies have identified cuproptosis and confirmed ferroptosis as significant factors in stroke pathology, underscoring the importance of metal ions in stroke pathology, including abnormal ion transport, neurotoxicity, blood-brain barrier damage, and cell death. Additionally, it provides an overview of contemporary metal ion chelators and detection techniques, which may offer novel approaches to stroke treatment.

Loss of Dec1 inhibits alcohol-induced hepatic lipid accumulation and circadian rhythm disorder.

Chronic alcohol exposure increases liver damage such as lipid accumulation and hepatitis, resulting in hepatic cirrhosis. Chronic alcohol intake is known to disturb circadian rhythms in humans and animals. DEC1, a basic helix-loop-helix transcription factor, plays an important role in the circadian rhythm, inflammation, immune responses, and tumor progression. We have previously shown that Dec1 deficiency inhibits stresses such as periodontal inflammation and perivascular fibrosis of the heart. However, the significance of Dec1 deficiency in chronic alcohol consumption remains unclear. In the present study, we investigated whether the biological stress caused by chronic alcohol intake is inhibited in Dec1 knockout mice. We treated control and Dec1 knockout mice for three months by providing free access to 10% alcohol. The Dec1 knockout mice consumed more alcohol than control mice, however, we observed severe hepatic lipid accumulation and circadian rhythm disturbance in control mice. In contrast, Dec1 knockout mice exhibited little effect on these outcomes. We also investigated the expression of peroxisome proliferator-activated receptors (PPARs) and AMP-activated protein kinase (AMPK), which are involved in the regulation of fatty acid metabolism. Immunohistochemical analysis revealed increases of phosphorylation AMPK and PPARa but decreases PPARg in Dec1 knockout mice compared to that in control mice. This indicates a molecular basis for the inhibition of hepatic lipid accumulation in alcohol-treated Dec1 knockout mice. These results suggest a novel function of Dec1 in alcohol-induced hepatic lipid accumulation and circadian rhythm disorders.

Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications.

Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways. This article provides an overview of the enriched environment protocols used in animal models of ischemic stroke, ICH, and TBI, as well as relevant clinical studies, with a particular focus on ischemic stroke. Additionally, we explored studies of animals with stroke and TBI exposed to EE alone or in combination with multiple drugs and other rehabilitation modalities. Finally, we discuss the potential clinical applications of EE in future brain rehabilitation therapy and the molecular and cellular changes caused by EE in rodents with stroke or TBI. This article aims to advance preclinical and clinical research on EE rehabilitation therapy for acquired brain injury. © 2024 American Physiological Society. Compr Physiol 14:5291-5323, 2024.

Histological analysis of a Becker muscular dystrophy case, diurnal expression of dystrophin in control mice and decreased expression of dystrophin in Bmal1 knockout mice.

Becker muscular dystrophy (BMD) is a hereditary disease characterized by dystrophin deletion that consequently induces muscle weakness, cardiac hypertrophy and cardiac failure; These conditions are similar to those in Duchenne muscular dystrophy. The circadian rhythm is a physiological phenomenon that is predominantly regulated by the transcription and translation of clock genes. Bmal1 (Brain and muscle Arnt-like protein 1) is one of the core clock genes, and its deficiency disturbs the circadian rhythm, results in cardiac hypertrophy and cardiac failure. Dystrophin expression under diurnal conditions and in Bmal1 deficiency is yet to be elucidated. In this study, we analyzed the heart and lungs sampled during a BMD autopsy. Macroscopical examination revealed a large heart and dilated cardiomyopathy. Microscopical examination revealed an undulated structure, as well as the degeneration, and necrosis of myocardial cells. We also analyzed dystrophin expression in tissues obtained from human autopsies and mice. In human autopsy cases, dystrophin expression was lower in the heart with BMD compared that in the heart with non-BMD hypertrophy. In the heart and muscle of control mice, dystrophin expression was higher at ZT0 than at ZT12. The dystrophin expression was found to be lower in heart-specific Bmal1 knockout mice compared to that in the control mice. Hence, our study indicated that BMD was closely associated with cardiac hypertrophy and cardiac failure, while dystrophin had a diurnal expression pattern in control mice that was regulated by Bmal1.

Crosstalk between microRNA-21-5p and the transcription factor Dec1 maintains osteoblast function.

MicroRNAs are associated with pivotal post-transcriptional gene regulation in bone formation. Human differentiated embryonic chondrocyte expressed gene 1 (Dec1) is also involved in regulating osteoblastogenesis. In the present study, we aimed to investigate the distinctive role of miR-21-5p and Dec1 in osteoblast function and to determine their biological functions. MC3T3-E1 pre-osteoblastic cells were used for in vitro analyses. miR-21-5p knockout (KO) mice, Dec1KO mice and age-matched wild-type (WT) mice were used to characterize the influence of miR-21-5p and Dec1 deficiencies on bone formation. Morphological analyses [micro-computed tomography (micro-CT)] were performed, and measurements were collected to validate miR-21-5pKO mice. Histopathological changes in mouse femur tissues were assessed by H-E staining, Azan staining, Masson's Trichrome staining, and Toluidine Blue staining. Quantitative real-time RT-PCR, western blotting and immunohistochemical staining were used to characterize the expression levels of Alkaline Phosphatase, Runx2, Osterix, Osteopontin, Dec1 and miR-21-5p. Bioinformatics analyses and dual-luciferase reporter assays were performed to confirm Dec1 as a target of miR-21-5p. Dec1 expression was gradually increased from day 7 of osteoblast induction, while miR-21-5p showed a peak at day 21. In non-induced osteoblasts, a mechanistically gain-of-function transfection study with a miR-21-5p mimic enhanced Runx2 and Osterix expression but suppressed Dec1. miR-21-5pKO mice had reduced bone growth. Dec1-deficient mice showed advanced bone formation at the age of 12 weeks compared to WT mice. The Dec1 deficiency upregulated Runx2 and Osterix expression in Dec1KO mouse femurs. Those changes, however, were reversed in miR-21-5pKO mouse femurs compared to WT mouse femurs. Dual-luciferase reporter assays showed that Dec1 is a possible downstream target of miR-21-5p. These findings showed that the reduced osteogenic potential due to a miR-21-5p deficiency is achieved by enhanced Dec1 expression and that the miR-21-5p/Dec1 axis is involved in regulating osteoblast function.

A novel hypoxia-driven gene signature that can predict the prognosis and drug resistance of gliomas.

Hypoxia spontaneously forms in the interior of glioma tissues and regulates the expression of various genes. However, the status of hypoxia-driven genes in glioma tissues is not completely known. In the current study, RNA-seq data of 695 glioma tissues in The Cancer Genome Atlas (TCGA) were set as a discovery cohort and were used to identify hypoxia-driven genes and construct a novel gene signature. The prognostic values of that signature were verified in data from the TCGA and the Chinese Glioma Genome Atlas (CGGA). The expression and diagnostic values of hypoxia-driven genes were analyzed using immunohistochemistry and receiver operator characteristic curves. Finally, the effects of hypoxia-driven genes on temozolomide (TMZ) resistance were analyzed by western blot, CCK-8 and colony formation assay. A total of 169 hypoxia-driven genes were identified, which were associated with a poor outcome in glioma patients. Among them, 22 genes had a degree score ≥10 and 6 genes (WT1, HOXA2, HOXC6, MMP9, SHOX2 and MYOD1) were selected to construct a signature to classify glioma patients into low- or high-risk groups. That signature had a remarkable prognostic value for glioma patients in TCGA and CGGA. The expression of HOXC6, MMP9, SHOX2 and MYOD1 was associated with hypoxia degree in glioma tissues and in recurrent cases, had a remarkable diagnostic value and a significant relationship with disease free survival in glioma patients. Moreover, SHOX2 was highly expressed in glioma tissues with O-6-methylguanine-DNA methyltransferase (MGMT)-unmethylation and temozolomide (TMZ) resistant glioma cell lines, and associated with MGMT expression. Knockdown the expression of SHOX2 significantly reduced the TMZ-resistance induced by hypoxia in glioma cells. Ultimately, we identified six novel hypoxia-driven genes for reliable prognostic prediction in gliomas and found that SHOX2 might be a potential target to overcome the TMZ resistance induced by hypoxia.

Dec2 negatively regulates bone resorption in periodontitis.

BACKGROUND AND OBJECTIVES: The potential role of the transcription factor Differentiated embryo-chondrocyte 2 (Dec2) in the progression of inflammatory diseases such as periodontitis has been unclear. Here, the effect of Dec2 on the expression of RANKL and on osteoclastogenesis was determined. MATERIAL AND METHODS: Wild-type (WT) and Dec2 knockout (KO) mice as a model for periodontitis were used to assess alveolar bone resorption by microcomputed tomography (CT). Western blot, flow cytometry, quantitative real-time PCR, and immunohistochemical analyses were utilized to detect inflammation and osteoclasts. Luciferase reporter and Chromatin immunoprecipitation (ChIP) assays examined the interaction between Dec2 and RANKL. RESULTS: Micro-CT showed that the alveolar bone resorption of Dec2KO mice was more severe than WT mice after treatment with P. gingivalis. Immunohistochemistry and Tartrate-resistant acid phosphatase staining showed active osteoclast differentiation in Dec2KO mice. There was an increase in CD11b+ F4/80+ and CD4+ RANKL+ T cells in Dec2KO mice treated with P. gingivalis. Moreover, inflammatory and immune markers were expressed at significantly higher levels in gingival mononuclear cells in Dec2KO mice. Furthermore, luciferase reporter and ChIP assays confirmed the direct binding of Dec2 protein to the RANKL gene. CONCLUSION: Dec2 has an immune regulation ability that modulates P. gingivalis-induced periodontitis via RANKL.

CCDC106 promotes the proliferation and invasion of ovarian cancer cells by suppressing p21 transcription through a p53-independent pathway.

Ovarian cancers are the major cause of mortality for women worldwide. This study was aimed to elucidate the biological activities of CCDC106 in the proliferation and invasion of mutant p53 and of wild-type p53 ovarian cancer cells. CAOV3 (mutant p53) cells showed high expression levels of CCDC106, but it was expressed at low levels in SKOV3 (mutant p53) and in A2780 (wild-type p53) cells. The overexpression of CCDC106 promoted the expression of proliferation markers (cyclin family members), invasion and Epithelial-to-mesenchymal transition (EMT) markers (claudin-1, claudin-4, N-cadherin, snail, slug) while the knockdown of CCDC106 inhibited their expression in mutant p53 cells but not in wild-type p53 cells. Treatment with a CK2 inhibitor blocked the translocation of CCDC106 into the nuclei of mutant p53 cells. Immunoprecipitation assays confirmed that ATF4 is a potential binding partner of CCDC106. The overexpression of CCDC106 reduced p21 and p27 protein expression levels while treatment with an ATF4 siRNA rescued their expression. The overexpression of CCDC106 promoted colony formation and invasion of mutant p53 cells, which was suppressed by treatment with an ATF4 siRNA. Immunohistochemistry results showed that CCDC106 and ATF4 are expressed at high levels but p21 is expressed at low levels in FIGO III-IV stage and in mutant p53 ovarian cancer samples. A significant association between poor overall survival and high CCDC106 and ATF4 expression levels was observed in human ovarian cancer samples. In conclusion, CCDC106 promotes proliferation, invasion and EMT of mutant p53 ovarian cancer cells via the ATF4 mediated inhibition of p21.

Role of Nanoparticles in Environmental Remediation: An Insight into Heavy Metal Pollution from Dentistry.

Environmental damage is without a doubt one of the most serious issues confronting society today. As dental professionals, we must recognize that some of the procedures and techniques we have been using may pose environmental risks. The usage and discharge of heavy metals from dental set-ups pollute the environment and pose a serious threat to the ecosystem. Due to the exclusive properties of nanosized particles, nanotechnology is a booming field that is being extensively studied for the remediation of pollutants. Given that the nanoparticles have a high surface area to volume ratio and significantly greater reactivity, they have been greatly considered for environmental remediation. This review aims at identifying the heavy metal sources and their environmental impact in dentistry and provides insights into the usage of nanoparticles in environmental remediation. Although the literature on various functions of inorganic nanoparticles in environmental remediation was reviewed, the research is still confined to laboratory set-ups and there is a need for more studies on the usage of nanoparticles in environmental remediation.

Differential immunohistochemical expression of DEC1, CK­1ε, and CD44 in oral atypical squamous epithelium and carcinoma in situ.

Presence of nuclear atypia during histological investigation is often a cause of concern for pathologists while identifying tumor and non­tumor cells in a biopsy sample of oral mucosa. Nuclear atypia is observed in severe inflammation, ulcers and reactive changes. Therefore, additional methods, such as immunohistochemistry, may help precise diagnosis. When the atypia is suggestive of tumorous or reactive origin, the lesion is diagnosed as atypical squamous epithelium (ASE). When there is severe nuclear atypia in the mucosa, such as in disorders of nuclear polarity, large nuclei, and clear nucleolus, the lesion is diagnosed as carcinoma in situ (CIS). However, it is not easy to distinguish ASE and CIS using hematoxylin and eosin staining. The present study aimed to distinguish ASE from CIS using immunohistochemistry. A total of 32 biopsy samples of either ASE or CIS cases were selected and the level of casein kinase 1ε (CK­1ε), differentiated embryonic chondrocyte gene 1 (DEC1), proliferating cell nuclear antigen (PCNA) and CD44, which are four protein markers which have been previously linked to cancer progression, were analyzed. CK­1ε and CD44 expression was higher in CIS samples than in ASE samples. However, DEC1 expression was lower in CIS samples than in ASE samples. PCNA expression was not markedly different between the two groups. Additionally, it was found that DEC1­overexpressing cells had decreased levels of CK­1ε and CD44 compared with control cells, while CK­1ε­overexpressing cells had relatively unchanged levels of CD44, DEC1 and PCNA. These results suggested that DEC1 negatively regulates the expression of CK­1ε and CD44. Thus, DEC1, CK­1ε, and CD44 were identified as mechanistically linked and clinically relevant protein biomarkers, which could help distinguish ASE and CIS.

Dec2 inhibits macrophage pyroptosis to promote periodontal homeostasis.

PURPOSE: Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation. METHODS: Porphyromonas gingivalis lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a P. gingivalis-treated experimental periodontitis Dec2-knockout mouse model. RESULTS: Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1ß. Dec2 overexpression reduced IL-1ß expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. In vivo, P. gingivalis-challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1ß. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of P. gingivalis-challenged mice. CONCLUSIONS: Our findings indicate that Dec2 deficiency exacerbated P. gingivalis LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.

Biphasic Functions of Sodium Fluoride (NaF) in Soft and in Hard Periodontal Tissues.

Sodium fluoride (NaF) is widely used in clinical dentistry. However, the administration of high or low concentrations of NaF has various functions in different tissues. Understanding the mechanisms of the different effects of NaF will help to optimize its use in clinical applications. Studies of NaF and epithelial cells, osteoblasts, osteoclasts, and periodontal cells have suggested the significant roles of fluoride treatment. In this review, we summarize recent studies on the biphasic functions of NaF that are related to both soft and hard periodontal tissues, multiple diseases, and clinical dentistry.

Ribosomal Stress Couples with the Hypoxia Response in Dec1-Dependent Orthodontic Tooth Movement.

This study characterized the effects of a deficiency of the hypoxia-responsive gene, differentiated embryonic chondrocyte gene 1 (Dec1), in attenuating the biological function of orthodontic tooth movement (OTM) and examined the roles of ribosomal proteins in the hypoxic environment during OTM. HIF-1α transgenic mice and control mice were used for hypoxic regulation of periodontal ligament (PDL) fibroblasts. Dec1 knockout (Dec1KO) and wild-type (WT) littermate C57BL/6 mice were used as in vivo models of OTM. The unstimulated contralateral side served as a control. In vitro, human PDL fibroblasts were exposed to compression forces for 2, 4, 6, 24, and 48 h. HIF-1α transgenic mice had high expression levels of Dec1, HSP105, and ribosomal proteins compared to control mice. The WT OTM mice displayed increased Dec1 expression in the PDL fibroblasts. Micro-CT analysis showed slower OTM in Dec1KO mice compared to WT mice. Increased immunostaining of ribosomal proteins was observed in WT OTM mice compared to Dec1KO OTM mice. Under hypoxia, Dec1 knockdown caused a significant suppression of ribosomal protein expression in PDL fibroblasts. These results reveal that the hypoxic environment in OTM could have implications for the functions of Dec1 and ribosomal proteins to rejuvenate periodontal tissue homeostasis.

The roles of Y-box-binding protein (YB)-1 and C-X-C motif chemokine ligand 14 (CXCL14) in the progression of prostate cancer via extracellular-signal-regulated kinase (ERK) signaling.

The cold-shock protein Y-box-binding protein (YB)-1 regulates the expression of various chemokines and their receptors at the transcriptional level. Expression of the orphan chemokine CXCL14 is repressed by EGF induced signaling. The possible links between EGF-mediated YB-1 and CXCL14 as well as the functions of critical kinase pathways in the progression of prostate cancer have remained unexplored. Here we examined the correlation between YB-1 and CXCL14, and the ERK/AKT/mTOR pathways in prostate cancer. Knockdown of YB-1 decreased cyclinD1 expression with an upregulation of cleaved-PARP in human prostate cancer cells. EGF treatment upregulated phospho-YB-1 expression in a time-dependent manner, while treatment with an ERK inhibitor completely silenced its expression in prostate cancer cells. EGF treatment stimulates CyclinD1 and YB-1 phosphorylation in an ERK-dependent pathway. Positive and negative regulation of YB-1 and CXCL14 was observed after EGF treatment in prostate cancer cells, respectively. EGF rescues cell cycle and apoptosis via the AKT and ERK pathways. Furthermore, YB-1 silencing induces G1 arrest and apoptosis, while knockdown of CXCL14 facilitates cell growth and inhibits apoptosis in prostate cancer cells. YB-1 and CXCL14 were inversely correlated in prostate cancer cells and tissues. A significant association between poor overall survival and High YB-1 expression was observed in human prostate cancer patients. In conclusion, our data reveal the functional relationship between YB-1 and CXCL14 in EGF mediated ERK signaling, and YB-1 expression is a significant prognostic marker to predict prostate cancer.

The Potential Roles of Dec1 and Dec2 in Periodontal Inflammation.

Periodontal inflammation is a common inflammatory disease associated with chronic inflammation that can ultimately lead to alveolar attachment loss and bone destruction. Understanding autophagy and pyroptosis has suggested their significant roles in inflammation. In recent years, studies of differentiated embryo-chondrocyte expressed genes 1 and 2 (Dec1 and Dec2) have shown that they play important functions in autophagy and in pyroptosis, which contribute to the onset of periodontal inflammation. In this review, we summarize recent studies on the roles of clock genes, including Dec1 and Dec2, that are related to periodontal inflammation and other diseases.

Bio-functionalized titanium surfaces with modified silk fibroin carrying titanium binding motif to enhance the ossific differentiation of MC3T3-E1.

Silk fibroin (SF) from Bombyx mori has superior properties as both a textile and a biomaterial, and has been used to functionalize the surfaces of various medical inorganic materials including titanium (Ti). In this study, we endowed SF with reversible binding ability to Ti by embedding a titanium binding motif (minTBP-1 and RKLPDA). Artificial SF proteins were first created by conjugating gene cassettes for SF motif (AGSGAG) and minTBP-1 motif with different ratios, which have been shown to bind reversibly to Ti surfaces in quartz crystal microbalance analyses. Based on these results, the functionalized SF (TiBP-SF) containing the designed peptide [TS[(AGSGAG)3 AS]2 RKLPDAS]8 was prepared from the cocoon of transgenic B. mori, which accelerates the ossific differentiation of MC3T3-E1 cells when coated on titanium substrates. Thus, TiBP-SF presents an alternative for endowing the surfaces of titanium materials with osseointegration functionality, which would allow the exploration of potential applications in the medical field.

A deficiency of Dec2 triggers periodontal inflammation and pyroptosis.

BACKGROUND AND OBJECTIVES: Periodontal pathogens initiate various diseases and induce inflammatory host responses. The activation of inflammasomes triggers caspase-1 and interleukin (IL)-1ß-mediated pyroptosis via gasdermin D (GSDMD). Differentiated embryo chondrocyte 2 (Dec2) is a transcription repressor that controls the expression of genes involved in innate immune and inflammatory responses. However, the effects of Dec2 on inflammasome-induced pyroptosis in periodontal tissues remain elusive. This study aimed to characterize the activation of Dec2 inflammasomes that contribute to P. gingivalis lipopolysaccharide (LPS)-induced pyroptosis and its functional and regulatory importance in periodontal inflammation. MATERIALS AND METHODS: Human gingival fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPDLFs) were stimulated with P. gingivalis LPS in vitro. An experimental periodontitis mouse model (wild-type (WT) and Dec2KO) was established to profile periodontal pyroptosis. RESULTS: The results demonstrate that P. gingivalis LPS activates caspase-1, caspase-11, and NF-κB in HGFs and in HPDLFs. siRNA knockdown of Dec2 stimulated the induction and further upregulated LPS-induced pyroptosis in HGFs and HPDLFs, resulting in the release of IL-1ß. Further, a deficiency of Dec2 alleviated periodontal pyroptosis via the transcriptional induction of GSDMD. In addition, P. gingivalis-induced IL-1ß expression and Dec2-deficient mice subsequently increased the inflammatory effect of P. gingivalis in HGFs and in HPDLFs, confirming the importance of Dec2 in the activation of inflammasomes and the regulation of pyroptosis. CONCLUSION: Our results demonstrate that Dec2 alleviates periodontal pyroptosis by regulating the expression of NF-κB, caspase-1 and GSDMD, suggesting that Dec2 is a crucial component of inflammasome activation and subsequent pyroptosis.

Anti-aging effects of Korean Red Ginseng (KRG) in differentiated embryo chondrocyte (DEC) knockout mice.

BACKGROUND: The circadian rhythm is the internal clock that controls sleep-wake cycles, metabolism, cognition, and several processes in the body, and its disruption has been associated with aging. The differentiated embryo chondrocyte (Dec) gene is related to circadian rhythm. To our knowledge, there are no reports of the relationship between dec gene expression and KRG effect. Therefore, we treated Dec gene knockout (KO) aging mice with KRG to study anti-aging related effects and possible mechanisms. METHODS: We evaluated KRG and expression of Dec genes in an ototoxicity model. Dec genes expression in livers of aging mice was further analyzed. Then, we assessed the effects of DEC KO on hearing function in mice by ABR. Finally, we performed DNA microarray to identify KRG-related gene expression changes in mouse liver and assessed the results using KEGG analysis. RESULTS: KRG decreased the expression of Dec genes in ototoxicity model, which may contribute to its anti-aging efficacy. Moreover, KRG suppressed Dec genes expression in liver of wild type indicating inhibition of senescence. ABR test indicated that KRG improved auditory function in aging mouse, demonstrating KRG efficacy on aging related diseases. CONCLUSION: Finally, in KEGG analysis of 238 genes that were activated and 158 that were inhibited by KRG in DEC KO mice, activated genes were involved in proliferation signaling, mineral absorption, and PPAR signaling whereas the inhibited genes were involved in arachidonic acid metabolism and peroxisomes. Our data indicate that inhibition of senescence-related Dec genes may explain the anti-aging efficacy of KRG.

MicroRNA-21 facilitates osteoblast activity.

MicroRNAs are emerging as critical post-transcriptional modulators in bone remodeling, regulating the functions of osteoblasts and osteoclasts. Intercellular crosstalk between osteoblasts and osteoclasts is mediated by miR-21 that controls the bone homeostasis response, providing potential targets for the maintenance of osteoblast function. The aim of this study was to investigate the effects of miR-21 on osteoblast function, and to explore the underlying mechanism. Increased alkaline phosphatase (ALP) activity and accelerated matrix mineralization was observed in mouse pre-osteoblast MC3T3-E1 cells compared with the non-induction (control) group. MiR-21 positively regulates osteogenic differentiation and mineralization by facilitating the expression of key osteogenic factors (ALP, Runx2, Osteopontin (OPN), Osterix (OSX) and Mef2c) in MC3T3-E1 cells. Furthermore, a deficiency of miR-21 suppresses the expression of those factors at both the mRNA and protein levels, indicating that miR-21 is a positive regulator of osteoblastic differentiation. H-E staining, Azan staining, Masson's Trichrome staining and Toluidine blue staining were performed in jaw and femur tissues of miR-21 knockout (miR-21KO) and wild-type (WT) mice. Immunohistochemical staining revealed substantially lower levels of ALP, Runx2 and OSX expression in jaw and femur tissues of miR-21KO mice. A similar trend was observed in femur tissues using quantitative real-time (RT) PCR. A total of 17 osteogenesis-related mRNAs were found to be differentially expressed in miR-21KO femur tissues using Mouse Gene Expression Microarray analysis. GeneSpring and Ingenuity Pathway Analysis revealed several potential target genes that are involved in bone remodeling, such as IL-1ß and HIF-1α. Several important pathways were determined to be facilitators of miR-21, which provides a reliable reference for future studies to elucidate the biological mechanisms of osteoblast function. Taken together, these results lead us to hypothesize a potential role for miR-21 in regulating osteoblast function, thus representing a potential biomarker of osteogenesis.