Efficacy and safety of bismuth quadruple regimens containing minocycline and vonoprazan for eradication of Helicobacter pylori: Real-world evidence.

Background and Aim: To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods: From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. Results: For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). Conclusions: The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.

Dysfunction of STING Autophagy Degradation in Senescent Nucleus Pulposus Cells Accelerates Intervertebral Disc Degeneration.

The pathogenesis of Intervertebral Disc Degeneration (IDD) is complex and multifactorial, with cellular senescence of nucleus pulposus (NP) cells and inflammation playing major roles in the progression of IDD. The stimulator of interferon genes (STING) axis is a key mediator of inflammation during infection, cellular stress, and tissue damage. Here, we present a progressive increase in STING in senescent NP cells with the degradation disorder. The STING degradation function in normal NP cells can prevent IDD. However, the dysfunction of STING degradation through autophagy causes the accumulation and high expression of STING in senescent NP cells as well as inflammation continuous activation together significantly promotes IDD. In senescent NP cells and intervertebral discs (IVDs), we found that STING autophagy degradation was significantly lower than that of normal NP cells and IVDs when STING was activated by 2'3'-cGAMP. Also, the above phenomenon was found in STINGgt/gt, cGAS-/- mice with models of age-induced, lumbar instability-induced IDD as well as found in the rat caudal IVD puncture models. Taken together, we suggested that the promotion of STING autophagy degradation in senescent NP Cells demonstrated a potential therapeutic modality for the treatment of IDD.

Nanoparticle-enhanced PD-1/PD-L1 targeted combination therapy for triple negative breast cancer.

Breast cancer with triple-negative subtype (TNBC) presents significant challenges with limited treatment options and a poorer prognosis than others. While PD-1/PD-L1 checkpoint inhibitors have shown promise, their efficacy in TNBC remains constrained. In recent years, nanoparticle (NP) technologies offer a novel approach to enhance cancer therapy by optimizing the tumor microenvironment and augmenting chemo- and immunotherapy effects in various preclinical and clinical settings. This review discusses recent investigations in NP strategies for improving PD-1/PD-L1 blockade-based combination therapy for TNBC. Those include single or multi-therapeutic NPs designed to enhance immunogenicity of the tumor, induce immunogenic cell death, and target immunosuppressive elements within the tumor microenvironment. The investigations also include NPs co-loaded with PD-L1 inhibitors and other therapeutic agents, leveraging targeted delivery and synergistic effects to maximize efficacy while minimizing systemic toxicity. Overall, NP approaches represent a promising avenue for enhancing PD-1/PD-L1 checkpoint blockade-based combination therapy in TNBC and encourage further developmental studies.

Demand analysis of general practice patients for teaching clinic based on Kano model.

Background: General practice teaching clinics play a crucial role in the training of general practitioners, as they are more likely to enhance reception skills compared to traditional training methods. The quality of teaching clinics is largely determined by the level of patient acceptance. In recent years, the Kano model has become increasingly popular in the healthcare industry and has been used to enhance patient satisfaction. The objective of this study is to apply the Kano model to investigate the needs of patients in general practice teaching clinics and to rank the significance of each demand. This study will serve as a reference for enhancing the service quality of teaching clinics and advancing the field of general practice. Methods: A total of 101 patients of general practice at the Affiliated Hospital of Yangzhou University in Jiangsu province were selected using a random convenience sampling method to participate in a questionnaire survey. The questionnaire was designed by members of our team and was based on the Kano model. The study defined the service demand, assessed the impact of both satisfaction and dissatisfaction and created a matrix bubble diagram. Results: The study findings revealed that out of the 14 items of the general practice teaching clinic service demands, 1 item was categorized as a must-be requirement, 4 items were categorized as one-dimensional requirements, 2 items were categorized as an attractive requirement, 2 items were categorized as an indifferent requirement, and 5 items were categorized as mixed attributes. The findings of the matrix analysis showed that 4 items were situated in the area of one-dimensional attributes quadrant, 3 items were situated in the area of attractive attributes quadrant, 5 items were situated in the area of indifferent attributes quadrant, and 2 items were situated in the area of must-be attributes quadrant. Conclusion: The patients of general practice have positive attitudes toward teaching clinics. The findings can offer valuable insights for enhancing the quality of service and patient experience in general practice teaching clinics as well as for advancing the field of general practice.

Dietary knowledge-attitude-practice status in hemodialysis patients: a latent profile analysis.

BACKGROUND: Hemodialysis patients require a reasonable dietary intake to manage their disease progression effectively. However, there is limited research on these patients' overall dietary knowledge, attitude, and practice (KAP) status. This study aimed to investigate the dietary KAP status and latent profiles in hemodialysis patients and identify sociodemographic and disease-related factors associated with these profiles and dietary practice. METHODS: A multicenter cross-sectional study involving 425 hemodialysis patients was conducted. A dietary KAP questionnaire in hemodialysis patients was used to evaluate the dietary KAP of the patients. A structural equation model was employed to analyze the correlations between dietary knowledge, attitude, and practice. Multiple linear regression analysis was used to identify factors associated with dietary practice scores. Latent profile analysis was conducted to determine the latent profiles of dietary KAP, and binary logistic regression was used to explore the sociodemographic and disease-related characteristics associated with each KAP profile in hemodialysis patients. RESULTS: The normalized average scores for dietary knowledge, attitude, and practice in hemodialysis patients were 0.58, 0.82, and 0.58, respectively. The structural equation model revealed significant positive correlations between dietary knowledge and attitude, and attitude and practice. Attitude played an indirect effect between knowledge and practice. Gender, cerebrovascular disease, and dietary attitude scores were identified as independent influencing factors for dietary practice scores. Two dietary KAP profiles were developed: a profile with general knowledge and attitude but low practice (40.2%) and a profile with general knowledge and attitude and high practice (59.8%). Binary logistic regression analysis indicated gender and monthly income per household significantly predicted membership in each KAP profile. CONCLUSIONS: The dietary practice of hemodialysis patients requires improvement. It is necessary to develop more individualized dietary interventions for these patients. Further exploration is needed to understand the motivation of patients to change their dietary behavior.

Favorable cervical extension capacity preventing loss of cervical lordosis after laminoplasty due to spontaneous restoration of initial lordosis.

BACKGROUND CONTEXT: Cervical laminoplasty is a common approach for the treatment of multilevel cervical spondylotic myelopathy (CSM). Postoperative loss of cervical lordosis (LCL) was associated with lower extension motion of the cervical spine before laminoplasty. PURPOSE: To analyze the possible causes of preoperative cervical extension capacity affecting LCL after laminoplasty by evaluating the changes in cervical lordosis (CL) at different stages. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: Seventy-two patients undergoing laminoplasty due to multilevel CSM. OUTCOME MEASURES: Radiographic parameters included CL, extension CL (eCL), flexion CL (fCL), range of motion (ROM), extension ROM (eROM), flexion ROM (fROM) and LCL. Clinical outcomes were assessed using the Japanese Orthopedic Association (JOA) and neck disability index (NDI) score. METHODS: The data were recorded before surgery and at 3- and 24-month follow-up. All patients completed a cervical extension test preoperatively. A receiver operating characteristic (ROC) curve of eROM was constructed to discriminate the patients with and without postoperative kyphotic deformity. RESULTS: According to the optimal cut-off value of eROM, the patients were divided into two groups: extension group (eROM≥9.3°) and control group (eROM<9.3°). The radiographic outcomes demonstrated no significant differences in CL, eCL, fCL and ROM between the two groups. Both eROM and fROM were significantly different in the two groups. There was a significant change in CL in the extension group at 3-month follow-up and in the control group at 24-month follow-up. The extension group exhibited significantly lower LCL compared with the control group at follow-up. No significant difference between the two groups was noted in the JOA recovery rate, while the NDI score was significantly different at 24-month follow-up. The positivity ratio of the extension test was significantly greater in the extension group than that in the control group. CONCLUSIONS: eROM in patients with favorable preoperative cervical extension capacity (eROM≥9.3°) consisted of the actual extension capacity and compensatory flexion. The cervical alignment would be spontaneously restored to its initial lordosis in the short term after laminoplasty. These patients had no substantial LCL at 24-month follow-up and would be good candidates for laminoplasty.

Recent strategies for evoking immunogenic Pyroptosis in antitumor immunotherapy.

Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including cell swelling, membrane blebbing, DNA fragmentation, and eventual cell lysis. Pyroptosis is closely associated with human-related diseases, such as inflammation and malignancies. Since the initial observation of pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, including ions, small molecules, and biological nanomaterials, have been developed for tumor treatment. Given that pyroptosis can activate the body's robust immune response against tumor and promote the formation of the body's long-term immune memory in tumor treatment, its status as a type of immunogenic cell death is self-evident. Therefore, pyroptosis should be used as a powerful anti-tumor strategy. However, there still is a lack of a comprehensive summary of the most recent advances in pyroptosis-based cancer therapy. Therefore, it is vital to fill this gap and inspire future drug design to better induce tumor cells to undergo pyroptosis to achieve advanced anti-tumor effects. In this review, we summarize in detail the most recent advances in triggering tumor cell immunogenic pyroptosis for adequate tumor clearance based on various treatment modalities, and highlight material design and therapeutic advantages. Besides, we also provide an outlook on the prospects of this emerging field in the next development.

Fast and adaptive dynamics-on-graphs to dynamics-of-graphs translation.

Numerous networks in the real world change with time, producing dynamic graphs such as human mobility networks and brain networks. Typically, the "dynamics on graphs" (e.g., changing node attribute values) are visible, and they may be connected to and suggestive of the "dynamics of graphs" (e.g., evolution of the graph topology). Due to two fundamental obstacles, modeling and mapping between them have not been thoroughly explored: (1) the difficulty of developing a highly adaptable model without solid hypotheses and (2) the ineffectiveness and slowness of processing data with varying granularity. To solve these issues, we offer a novel scalable deep echo-state graph dynamics encoder for networks with significant temporal duration and dimensions. A novel neural architecture search (NAS) technique is then proposed and tailored for the deep echo-state encoder to ensure strong learnability. Extensive experiments on synthetic and actual application data illustrate the proposed method's exceptional effectiveness and efficiency.

Repression of LSD1 potentiates homologous recombination-proficient ovarian cancer to PARP inhibitors through down-regulation of BRCA1/2 and RAD51.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are selectively active in ovarian cancer (OC) with homologous recombination (HR) deficiency (HRD) caused by mutations in BRCA1/2 and other DNA repair pathway members. We sought molecular targeted therapy that induce HRD in HR-proficient cells to induce synthetic lethality with PARPi and extend the utility of PARPi. Here, we demonstrate that lysine-specific demethylase 1 (LSD1) is an important regulator for OC. Importantly, genetic depletion or pharmacological inhibition of LSD1 induces HRD and sensitizes HR-proficient OC cells to PARPi in vitro and in multiple in vivo models. Mechanistically, LSD1 inhibition directly impairs transcription of BRCA1/2 and RAD51, three genes essential for HR, dependently of its canonical demethylase function. Collectively, our work indicates combination with LSD1 inhibitor could greatly expand the utility of PARPi to patients with HR-proficient tumor, warranting assessment in human clinical trials.

Pharmacological inhibition of LSD1 suppresses growth of hepatocellular carcinoma by inducing GADD45B.

Lysine-specific histone demethylase 1 (LSD1) is an attractive target for malignancies therapy. Nevertheless, its role in hepatocellular carcinoma (HCC) progression and the potential of its inhibitor in HCC therapy remains unclear. Here, we show that LSD1 overexpression in human HCC tissues is associated with HCC progression and poor patient survival. ZY0511, a highly selective and potent inhibitor of LSD1, suppressed human HCC cell proliferation in vitro and tumor growth in cell-derived and patient-derived HCC xenograft models in vivo. Mechanistically, ZY0511 induced mRNA expression of growth arrest and DNA damage-inducible gene 45beta (GADD45B) by inducing histone H3 at lysine 4 (H3K4) methylation at the promoter of GADD45B, a novel target gene of LSD1. In human HCC tissues, LSD1 level was correlated with a decreased level of GADD45B, which was associated with HCC progression and predicted poor patient survival. Moreover, co-administration of ZY0511 and DTP3, which specifically enhanced the pro-apoptotic effect of GADD45B, effectively inhibited HCC cell proliferation both in vitro and in vivo. Collectively, our study revealed the potential value of LSD1 as a promising target of HCC therapy. ZY0511 is a promising candidate for HCC therapy through upregulating GADD45B, thereby providing a novel combinatorial strategy for treating HCC.

A Benchmark Dataset of Endoscopic Images and Novel Deep Learning Method to Detect Intestinal Metaplasia and Gastritis Atrophy.

Endoscopy has been routinely used to diagnose stomach diseases including intestinal metaplasia (IM) and gastritis atrophy (GA). Such routine examination usually demands highly skilled radiologists to focus on a single patient with substantial time, causing the following two key challenges: 1) the dependency on the radiologist's experience leading to inconsistent diagnosis results across different radiologists; 2) limited examination efficiency due to the demanding time and energy consumption to the radiologist. This paper proposes to address these two issues in endoscopy using novel machine learning method in three-folds. Firstly, we build a novel and relatively big endoscopy dataset of 21,420 images from the widely used White Light Imaging (WLI) endoscopy and more recent Linked Color Imaging (LCI) endoscopy, which were annotated by experienced radiologists and validated with biopsy results, presenting a benchmark dataset. Secondly, we propose a novel machine learning model inspired by the human visual system, named as local attention grouping, to effectively extract key visual features, which is further improved by learning from multiple randomly selected regional images via ensemble learning. Such a method avoids the significant problem in the deep learning methods that decrease the resolution of original images to reduce the size of input samples, which would remove smaller lesions in endoscopy images. Finally, we propose a dual transfer learning strategy to train the model with co-distributed features between WLI and LCI images to further improve the performance. The experiment results, measured by accuracy, specificity, sensitivity, positive detection rate and negative detection rate, on IM are 99.18 %, 98.90 %, 99.45 %, 99.45 %, 98.91 %, respectively, and on GA are 97.12 %, 95.34 %, 98.90 %, 98.86 %, 95.50 %, respectively, achieving state of the art performance that outperforms current mainstream deep learning models.

Dignity therapy, psycho-spiritual well-being and quality of life in the terminally ill: systematic review and meta-analysis.

OBJECTIVES: Dignity therapy (DT) is a brief, individualised psychotherapy that aims to alleviate psychosocial and spiritual distress in the final stages of life. It is unknown yet whether DT can enhance sense of dignity and improve psychological and spiritual well-being as well as quality of life of terminally ill patients. METHODS: We searched PubMed, EMBASE, CINAHL plus, ProQuest Health & Medical Complete, PsycINFO and the Cochrane Library, as well as Chinese databases including Weipu Data, Wanfang Data and China National Knowledge Infrastructure from inception to 30 April 2021, for randomised controlled trials (RCTs) assessing the effects of DT on dignity, psycho-spiritual well-being and quality of life of terminally ill patients receiving palliative care. RESULTS: We identified 507 unique records, and included 9 RCTs (871 participants). Comparator was standard palliative care. DT did not improve terminally ill patients' sense of dignity (p=0.90), hope (p=0.15), spiritual well-being (p=0.99) and quality of life (p=0.23). However, DT reduced anxiety and depression after intervention (standardised mean difference, SMD=-1.13, 95% CI (-2.21 to -0.04), p=0.04; SMD=-1.22, 95% CI (-2.25 to -0.18), p=0.02, respectively) and at 4 weeks post-intervention (SMD=-0.89, 95% CI (-1.71 to -0.07), p=0.03; SMD=-1.26, 95% CI (-2.38 to -0.14), p=0.03, respectively). CONCLUSION: DT can be offered as a psychological intervention for terminally ill patients to reduce their anxiety and depression. More studies are needed to further evaluate the effects of DT on terminally ill patients' dignity, spiritual well-being and quality of life.

Development and Formative Evaluation of the Family-Based Dignity Therapy Protocol for Palliative Cancer Patients and Their Families: A Mixed-Methods Study.

BACKGROUND: Palliative cancer patients and family members in China may experience difficulties in expressing their feelings, concerns, and needs to each other because of the death-taboo culture and the strong desire to protect each other from being exposed to emotional distress. OBJECTIVES: The aims of this study were to develop a nurse-led psychotherapeutic intervention aiming to facilitate meaningful conversations between palliative cancer patients and their family members, named family-based dignity therapy (FBDT), and preliminarily explore the anticipated benefits and challenges of the implementation of FBDT. METHODS: A convergent parallel mixed-methods design was used. The FBDT was designed based on the dignity therapy protocol and additionally inspired by the Chinese tradition of "4 important things in life." Ten palliative cancer patients, 10 family members, and 13 oncology and hospice nurses were surveyed to evaluate the FBDT protocol both quantitatively and qualitatively. RESULTS: The FBDT interview guide was endorsed by most palliative cancer patients and family members (>75.0%), as well as oncology and hospice nurses (>90.0%). Potential perceived benefits and challenges of FBDT were proposed by participants. The FBDT protocol was modified according to feedback from participants to make it more suitable to use in clinical practice in China. CONCLUSION: The FBDT was perceived to be a potentially promising intervention to facilitate meaningful end-of-life conversations among palliative cancer patients and family members in China. IMPLICATIONS FOR PRACTICE: The FBDT might provide a means for nurses to promote potentially enhanced end-of-life communications for palliative cancer patients and their families. Further studies are needed to examine the feasibility, acceptability, and efficacy of FBDT to confirm this in China.

Development and Formative Evaluation of the Family-Based Dignity Therapy Protocol for Palliative Cancer Patients and Their Families: A Mixed-Methods Study.

BACKGROUND: Palliative cancer patients and family members in China may experience difficulties in expressing their feelings, concerns, and needs to each other because of the death-taboo culture and the strong desire to protect each other from being exposed to emotional distress. OBJECTIVES: The aims of this study were to develop a nurse-led psychotherapeutic intervention aiming to facilitate meaningful conversations between palliative cancer patients and their family members, named family-based dignity therapy (FBDT), and preliminarily explore the anticipated benefits and challenges of the implementation of FBDT. METHODS: A convergent parallel mixed-methods design was used. The FBDT was designed based on the dignity therapy protocol and additionally inspired by the Chinese tradition of "4 important things in life." Ten palliative cancer patients, 10 family members, and 13 oncology and hospice nurses were surveyed to evaluate the FBDT protocol both quantitatively and qualitatively. RESULTS: The FBDT interview guide was endorsed by most palliative cancer patients and family members (>75.0%), as well as oncology and hospice nurses (>90.0%). Potential perceived benefits and challenges of FBDT were proposed by participants. The FBDT protocol was modified according to feedback from participants to make it more suitable to use in clinical practice in China. CONCLUSION: The FBDT was perceived to be a potentially promising intervention to facilitate meaningful end-of-life conversations among palliative cancer patients and family members in China. IMPLICATIONS FOR PRACTICE: The FBDT might provide a means for nurses to promote potentially enhanced end-of-life communications for palliative cancer patients and their families. Further studies are needed to examine the feasibility, acceptability, and efficacy of FBDT to confirm this in China.

Glycosylation of viral proteins: Implication in virus-host interaction and virulence.

Glycans are among the most important cell molecular components. However, given their structural diversity, their functions have not been fully explored. Glycosylation is a vital post-translational modification for various proteins. Many bacteria and viruses rely on N-linked and O-linked glycosylation to perform critical biological functions. The diverse functions of glycosylation on viral proteins during viral infections, including Dengue, Zika, influenza, and human immunodeficiency viruses as well as coronaviruses have been reported. N-linked glycosylation is the most common form of protein modification, and it modulates folding, transportation and receptor binding. Compared to N-linked glycosylation, the functions of O-linked viral protein glycosylation have not been comprehensively evaluated. In this review, we summarize findings on viral protein glycosylation, with particular attention to studies on N-linked glycosylation in viral life cycles. This review informs the development of virus-specific vaccines or inhibitors.

Prussian Blue Nanoparticles Stabilize SOD1 from Ubiquitination-Proteasome Degradation to Rescue Intervertebral Disc Degeneration.

Discography often destroys the hypoxic environment in the intervertebral disc and accelerates intervertebral disc degeneration (IVDD). Therefore, it often fails to meet the requirements for application in clinical practice. This technology mainly increases the reactive oxygen species (ROS) in the IVD. As so, it is particularly critical to develop strategies to avoid this degeneration mechanism. Prussian blue nanoparticles (PBNPs) are found to enhance development under magnetic resonance T1 and have antioxidant enzyme activity. The key results of the present study confirm that PBNPs alleviate intracellular oxidative stress and increase the intracellular activities of antioxidant enzymes, such as superoxide dismutase 1 (SOD1). PBNPs can rescue nucleus pulposus cell degeneration by increasing oxidoreductase system-related mRNA and proteins, especially by stabilizing SOD1 from ubiquitination-proteasome degradation, thus improving the mitochondrial structure to increase antioxidation ability, and finally rescuing ROS-induced IVDD in a rat model. Therefore, it is considered that PBNPs can be a potential antioxidation-protective discography contrast agent.

DZNep promotes mouse bone defect healing via enhancing both osteogenesis and osteoclastogenesis.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is a novel oncogene that can specifically trimethylate the histone H3 lysine 27 (H3K27me3) to transcriptionally inhibit the expression of downstream tumor-suppressing genes. As a small molecular inhibitor of EZH2, 3-Deazaneplanocin (DZNep) has been widely studied due to the role of tumor suppression. With the roles of epigenetic regulation of bone cells emerged in past decades, the property and molecular mechanism of DZNep on enhancing osteogenesis had been reported and attracted a great deal of attention recently. This study aims to elucidate the role of DZNep on EZH2-H3K27me3 axis and downstream factors during both osteoclasts and osteoblasts formation and the therapeutic possibility of DZNep on bone defect healing. METHODS: Bone marrow-derived macrophages (BMMs) cells were cultured, and their responsiveness to DZNep was evaluated by cell counting kit-8, TRAP staining assay, bone resorption assay, podosome actin belt. Bone marrow-derived mesenchymal stem cells (BMSC) were cultured and their responsiveness to DZNep was evaluated by cell counting kit-8, ALP and AR staining assay. The expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), Wnt signaling pathway was determined by qPCR and western blotting. Mouse bone defect models were created, rescued by DZNep injection, and the effectiveness was evaluated by X-ray and micro-CT and histological staining. RESULTS: Consistent with the previous study that DZNep enhances osteogenesis via Wnt family member 1(Wnt1), Wnt6, and Wnt10a, our results showed that DZNep also promotes osteoblasts differentiation and mineralization through the EZH2-H3K27me3-Wnt4 axis. Furthermore, we identified that DZNep promoted the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation via facilitating the phosphorylation of IKKα/ß, IκB, and subsequently NF-κB nuclear translocation, which credit to the EZH2-H3K27me3-Foxc1 axis. More importantly, the enhanced osteogenesis and osteoclastogenesis result in accelerated mice bone defect healing in vivo. CONCLUSION: DZNep targeting EZH2-H3K27me3 axis facilitated the healing of mice bone defect via simultaneously enhancing osteoclastic bone resorption and promoting osteoblastic bone formation.

Nicorandil Inhibits Osteoclast Formation Base on NF-κB and p-38 MAPK Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss.

Osteolytic bone disorders are characterized by an overall reduction in bone mineral density which enhances bone ductility and vulnerability to fractures. This disorder is primarily associated with superabundant osteoclast formation and bone resorption activity. Nicorandil (NIC) is a vasodilatory anti-anginal drug with ATP-dependent potassium (KATP) channel openings. However, NIC is adopted to manage adverse cardiovascular and coronary events. Recent research has demonstrated that NIC also possesses anti-inflammatory peculiarity through the regulation of p38 MAPK and NF-κB signaling pathways. Both MAPK and NF-κB signaling pathways play pivotal roles in RANKL-induced osteoclast formation and bone resorption function. Herein, we hypothesized that NIC may exert potential biological effects against osteoclasts, and revealed that NIC dose-dependently suppressed bone marrow macrophage (BMM) precursors to differentiate into TRAP + multinucleated osteoclasts in vitro. Furthermore, osteoclast resorption assays demonstrated anti-resorptive effects exhibited by NIC. NIC had no impact on osteoblast differentiation or mineralization function. Based on Biochemical analyses, NIC relieved RANKL-induced ERK, NF-κB and p38 MAPK signaling without noticeable effects on JNK MAPK activation. However, the attenuation of NF-κB and p38 MAPK activation was sufficient to hamper the downstream induction of c-Fos and NFATc1 expression. Meanwhile, NIC administration markedly protected mice from ovariectomy (OVX)-induced bone loss through in vivo inhibition of osteoclast formation and bone resorption activity. Collectively, this work demonstrated the potential of NIC in the management of osteolytic bone disorders mediated by osteoclasts.