Germacrone alleviates breast cancer-associated osteolysis by inhibiting osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways.

Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti-cancer and anti-inflammation agent, but its effect on breast cancer-induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer-induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F-actin ring formation, and gene expression were examined in vitro. RNA-sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer-induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro-CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F-actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast-related genes. RNA-seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA-MB-231 cells. Furthermore, GM could inhibit MDA-MB-231 cell-induced osteoclastogenesis in vitro and alleviate breast cancer-associated osteolysis in vivo human MDA-MB-231 breast cancer bone metastasis-bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis.

Proposal for a classification system of radiographic bone changes after cervical disc replacement.

BACKGROUND: The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR. METHODS: Aided by serial plain radiographs from recent cTDR cases (34 patients; 44 devices), a panel of experts assembled for the purpose of creating a classification system to aid in reproducibly and accurately identifying bony changes and assessing cTDR radiographic appearance. Subdividing the superior and inferior vertebral bodies into 3 equal sections, observed bone loss such as endplate rounding, cystic erosion adjacent to the endplate, and cystic erosion not adjacent to the endplate, is recorded. Determining if bone loss is progressive, based on serial radiographs, and estimating severity of bone loss (measured by the percentage of end plate involved) is recorded. Additional relevant bony changes and device observations include radiolucent lines, heterotopic ossification, vertebral body olisthesis, loss of core implant height, and presence of device migration, and subsidence. RESULTS: Serial radiographs from 19 patients (25 devices) implanted with a variety of cTDR designs were assessed by 6 investigators including clinicians and scientists experienced in cTDR or appendicular skeleton joint replacement. The overall agreement of assessments ranged from 49.9% (95% bootstrap confidence interval 45.1-73.1%) to 94.7% (95% CI 86.9-100.0%). There was reasonable agreement on the presence or absence of bone loss or radiolucencies (range: 58.4% (95% CI 51.5-82.7%) to 94.7% (95% CI 86.9-100.0%), as well as in the progression of radiolucent lines (82.9% (95% CI 74.4-96.5%)). CONCLUSIONS: The novel classification system proposed demonstrated good concordance among experienced investigators in this field and represents a useful advancement for improving reporting in cTDR studies.

Effects of apical periodontitis treatment on hyperglycaemia in diabetes: A prospective cohort study.

AIM: This prospective cohort study was undertaken to evaluate the success rate of root canal treatment (RCT) in type 2 diabetes mellitus (T2DM) patients with targeted level and unachieved targeted level of glycaemic control as well as the impact of RCT on the glucose blood level in T2DM patients. METHODOLOGY: Patients needing RCT were divided into three groups: these without T2DM, that is, the control group (CG), those with targeted level of glycated haemoglobin HbA1c < 7% (TL A1c) and the third ones with unachieved targeted level (UTL A1c), that is, with HbA1c ≥ 7%. Before RCT, HbA1c and the periapical index (PAI) score were assessed, as well as 1 year later. RESULTS: Our results showed less favourable treatment results of RCT such as a reduction of radiographic lesions in T2DM patients, particularly in subjects with UTL A1c. The intergroup analysis of PAI score at the 12-month follow-up revealed a significant difference in TL A1C (p = .022) and CG (p = .001) with respect to UTL A1c. Total number of healed teeth (PAI≤2) at the 12-month after RCT in UTL A1c was significantly lower in comparison to CG (p = .008). Contrariwise, RCT may improve the glycaemic control in diabetic patients with UTL A1c after 12 months of posttreatment. Regression analysis showed that UTL A1c patients were more likely to have AP persistence after endodontic treatment (OR = 4.788; CI: 1.157-19.816; p = .031). CONCLUSIONS: T2DM retards the AP healing and conversely AP contributes to increasing the inflammatory burden in T2DM. RCT reduces the cumulative inflammatory burden in T2DM and thus may contribute to improvement of glycaemic control particularly in patients with UTL A1c.

A mechanobiological model of bone metastasis reveals that mechanical stimulation inhibits the pro-osteolytic effects of breast cancer cells.

Bone is highly susceptible to cancer metastasis, and both tumor and bone cells enable tumor invasion through a "vicious cycle" of biochemical signaling. Tumor metastasis into bone also alters biophysical cues to both tumor and bone cells, which are highly sensitive to their mechanical environment. However, the mechanobiological feedback between these cells that perpetuate this cycle has not been studied. Here, we develop highly advanced in vitro and computational models to provide an advanced understanding of how tumor growth is regulated by the synergistic influence of tumor-bone cell signaling and mechanobiological cues. In particular, we develop a multicellular healthy and metastatic bone model that can account for physiological mechanical signals within a custom bioreactor. These models successfully recapitulated mineralization, mechanobiological responses, osteolysis, and metastatic activity. Ultimately, we demonstrate that mechanical stimulus provided protective effects against tumor-induced osteolysis, confirming the importance of mechanobiological factors in bone metastasis development.

Subacromial osteolysis following hook plate fixation for acromioclavicular dislocation: a systematic review and meta-analysis.

BACKGROUND: Clavicular hook plates are extensively used in the treatment of acromioclavicular (AC) dislocation. Subacromial osteolysis is a typical complication following hook plate fixation. We performed a systematic review and meta-analysis to determine the incidence of subacromial osteolysis and analyzed the associated characteristics of subacromial osteolysis to guide surgeons. METHODS: PubMed, EMBASE, and Cochrane Library databases were comprehensively searched for relevant literature. We screened the literature based on the eligibility criteria, extracted relevant data and assessed the quality of the included studies. Pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals were calculated by a fixed-effects or random-effects model. Heterogeneity was evaluated by the chi-squared test and I2 statistics. A meta-regression analysis was performed to explore the potential source of heterogeneity. RESULTS: Thirty-two studies met the inclusion criteria. The total pooled incidence of subacromial osteolysis was 29%, and the only covariate that could influence the incidence of subacromial osteolysis was the radiological measurement method (P=0.017). Patients in the hook plate fixation with coracoclavicular (CC) ligament reconstruction group had lower odds of subacromial osteolysis (OR, 2.54, 95% CI 1.54 to 4.18; P < 0.001). There were no significant differences in the Constant-Murley scores at the final follow-up between patients with and without subacromial osteolysis (SMD, -0.17; 95% CI, -0.50 to 0.15; P= 0.294). CONCLUSIONS: Subacromial osteolysis has a relatively high and variable incidence, and the primary factor influencing the reported incidence is the radiological assessment method. The current analysis suggests CC ligament reconstruction as an effective surgical approach for decreasing the incidence of subacromial osteolysis. The presence or absence of subacromial osteolysis did not significantly impact the functional outcomes observed during the final follow-up period.

Estradiol induces bone osteolysis in triple-negative breast cancer via its membrane-associated receptor ERα36.

Triple-negative breast cancer (TNBC) is thought to be an estradiol-independent, hormone therapy-resistant cancer because of lack of estrogen receptor alpha 66 (ERα66). We identified a membrane-bound splice variant, ERα36, in TNBC cells that responds to estrogen (E2) and may contribute to bone osteolysis. We demonstrated that the MDA-MB-231 TNBC cell line, which expresses ERα36 similarly to MCF7 cells, is responsive to E2, forming osteolytic tumors in vivo. MDA-MB-231 cells activate osteoclasts in a paracrine manner. Conditioned media (CM) from MDA-MB-231 cells treated with bovine serum albumin-bound E2 (E2-BSA) increased activation of human osteoclast precursor cells; this was blocked by addition of anti-ERα36 antibody to the MDA-MB-231 cultures. Osteoclast activation and bone resorption genes were elevated in RAW 264.7 murine macrophages following treatment with E2-BSA-stimulated MDA-MB-231 CM. E2 and E2-BSA increased phospholipase C (PLC) and protein kinase C (PKC) activity in MDA-MB-231 cells. To examine the role of ERα36 signaling in bone osteolysis in TNBC, we used our bone-cancer interface mouse model in female athymic homozygous Foxn1nu mice. Mice with MDA-MB-231 tumors and treated with tamoxifen (TAM), E2, or TAM/E2 exhibited increased osteolysis, cortical bone breakdown, pathologic fracture, and tumor volume; the combined E2/TAM group also had reduced bone volume. These results suggest that E2 increased osteolytic lesions in TNBC through a membrane-mediated PLC/PKC pathway involving ERα36, which was enhanced by TAM, demonstrating the role of ERα36 and its membrane-associated signaling pathway in bone tumors. This work suggests that ERα36 may be a potential therapeutic target in patients with TNBC.

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner.

Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lacking Fndc5 (knockout [KO]), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet. Male KO mice have more but weaker bone compared to WT males, and when challenged with a low-calcium diet lost more bone than WT males. To begin to understand responsible molecular mechanisms, osteocyte transcriptomics was performed. Osteocytes from WT females had greater expression of genes associated with osteocytic osteolysis and osteoclastic bone resorption compared to WT males which had greater expression of genes associated with steroid and fatty acid metabolism. Few differences were observed between female KO and WT osteocytes, but with a low-calcium diet, the KO females had lower expression of genes responsible for osteocytic osteolysis and osteoclastic resorption than the WT females. Male KO osteocytes had lower expression of genes associated with steroid and fatty acid metabolism, but higher expression of genes associated with bone resorption compared to male WT. In conclusion, irisin plays a critical role in the development of the male but not the female skeleton and protects male but not female bone from calcium deficiency. We propose irisin ensures the survival of offspring by targeting the osteocyte to provide calcium in lactating females, a novel function for this myokine.

Angiopoietin 1 Relieves Osteolysis by Promoting Macrophage Mitophagy Through the TBK1-SQSTM1 Pathway to Inhibit AIM2 Inflammasome-Mediated Pyroptosis.

Osteolysis resulting from wear particles and subsequent aseptic loosening is a leading cause of revision surgery of artificial joints. The underlying pathogenesis of particle-induced osteolysis (PPO) has remained largely uncertain. Addressing how to mitigate osteolysis caused by wear particles presents a significant challenge for orthopedic surgeons. This study aimed to explore the molecular mechanism by which Angiopoietin (Ang-1) inhibits osteoclast activation to alleviate osteolysis. RAW264.7 mouse macrophages were stimulated with LPS or RANKL to induce osteoclast formation. Additionally, titanium (Ti) particles (50 mg) were subperiosteally implanted around the cranial suture of mice to establish a calvarial osteolysis model. Ang-1, a member of the pro-angiogenic factor protein family and an important inflammatory regulator molecule, was utilized in this model. TRAP staining was utilized to detect osteoclast activation, while a western blot was conducted to identify key proteins associated with mitophagy and pyroptosis. Scanning electron microscopy was employed to observe the morphology and dimensions of Ti particles. Additionally, a combination of micro-CT, H&E, Masson's trichrome, and immunohistochemical staining techniques were applied to analyze the calvarial samples. Results indicated that Ang-1 could inhibit LPS- or RANKL-induced osteoclastogenesis and alleviate Ti particle-induced calvarial osteolysis in mice. TBK-1, a key signaling molecule involved in initiating mitophagy, was found to be mechanistically enhanced by Ang-1 through promoting TBK-1 phosphorylation in macrophages. This process inhibited AIM2 inflammasome-mediated pyroptosis and impeded osteoclastogenesis. Overall, this research uncovers a novel mechanism by which Ang-1 can attenuate inflammatory osteolysis, potentially offering a new therapeutic approach for PPO.

The Function and Mechanism of Anti-Inflammatory Factor Metrnl Prevents the Progression of Inflammatory-Mediated Pathological Bone Osteolytic Diseases.

Metrnl, recently identified as an adipokine, is a secreted protein notably expressed in white adipose tissue, barrier tissues, and activated macrophages. This adipokine plays a pivotal role in counteracting obesity-induced insulin resistance. It enhances adipose tissue functionality by promoting adipocyte differentiation, activating metabolic pathways, and exerting anti-inflammatory effects. Extensive research has identified Metrnl as a key player in modulating inflammatory responses and as an integral regulator of muscle regeneration. These findings position Metrnl as a promising biomarker and potential therapeutic target in treating inflammation-associated pathologies. Despite this, the specific anti-inflammatory mechanisms of Metrnl in immune-mediated osteolysis and arthritis remain elusive, warranting further investigation. In this review, we will briefly elaborate on the role of Metrnl in anti-inflammation function in inflammation-related osteolysis, arthritis, and pathological bone resorption, which could facilitate Metrnl's clinical application as a novel therapeutic strategy to prevent bone loss. While the pathogenesis of elbow stiffness remains elusive, current literature suggests that Metrnl likely exerts a pivotal role in its development.

Calycosin alleviates titanium particle-induced osteolysis by modulating macrophage polarization and subsequent osteogenic differentiation.

Periprosthetic osteolysis (PPO) caused by wear particles is one of the leading causes of implant failure after arthroplasty. Macrophage polarization imbalance and subsequent osteogenic inhibition play a crucial role in PPO. Calycosin (CA) is a compound with anti-inflammatory and osteoprotective properties. This study aimed to evaluate the effects of CA on titanium (Ti) particle-induced osteolysis, Ti particle-induced macrophage polarization and subsequent osteogenic deficits, and explore the associated signalling pathways in a Ti particle-stimulated calvarial osteolysis mouse model using micro-CT, ELISA, qRT-PCR, immunofluorescence and western blot techniques. The results showed that CA alleviated inflammation, osteogenic inhibition and osteolysis in the Ti particle-induced calvarial osteolysis mouse model in vivo. In vitro experiments showed that CA suppressed Ti-induced M1 macrophage polarization, promoted M2 macrophage polarization and ultimately enhanced osteogenic differentiation of MC3T3-E1 cells. In addition, CA alleviated osteogenic deficits by regulating macrophage polarization homeostasis via the NF-κB signalling pathway both in vivo and in vitro. All these findings suggest that CA may prove to be an effective therapeutic agent for wear particle-induced osteolysis.

Morusin inhibits breast cancer-induced osteolysis by decreasing phosphatidylinositol 3-kinase (PI3K)-mTOR signalling.

Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo. To identify potential MOR treatments, the active ingredient-target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo, indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo. MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.

Intracranial invasion of a mast cell tumour in a dog: A case report and review of the literature.

An 11-year-old, female-neutered beagle was presented with a growing soft tissue mass arising within the deep tissues of the left cranial cervical region. At presentation, facial asymmetry was evident along with palpable lymphadenomegaly. Magnetic resonance imaging demonstrated a locally invasive cervical mass with intracranial invasion through focal osteolysis of the occipital bone. After antihistamine administration, cytology confirmed mast cell tumour (MCT) with metastasis to local lymph nodes and liver. The owner chose to pursue lomustine and prednisolone, which were dispensed, but, before home administration, prolonged seizures/status epilepticus occurred prompting euthanasia. Postmortem examination confirmed a high-grade MCT associated with, and infiltrating through, muscle, calvarium, dura mata, leptomeninges and the underlying brain. We present the clinical, imaging, and pathological findings of an unprecedented case of extracranial MCT tumour causing osteolysis of an imperforate flat bone (occipital bone) and intracranial invasion.

A case report of multicentric carpotarsal osteolysis syndrome: Depiction of a debilitating disease course.

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by progressive osteolysis involving the carpal and tarsal bones, and often associated with nephropathy. It is caused by heterozygous mutation in the MAF bZIP transcription factor B (MAFB) gene. Heterogeneous clinical manifestation and wide spectrum of disease severity have been observed in patients with MCTO. Here, we report a case of a male patient who presented with kidney failure in childhood with progressive disabling skeletal deformity. He was diagnosed with MCTO at 31-years-old, where a de novo pathogenic heterozygous variant in NM_005461.5:c.212C>A: p.(Pro71His) of the MAFB gene was identified. While there has been little data on the long-term prognosis and life expectancy of this disease, this case report sheds light on the debilitating disease course with multiple significant morbidities of a patient with MCTO throughout his lifetime of 33 years.

Epiberberine inhibits bone metastatic breast cancer-induced osteolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The anti-tumor related diseases of Coptidis Rhizoma (Huanglian) were correlated with its traditional use of removing damp-heat, clearing internal fire, and counteracting toxicity. In the recent years, Coptidis Rhizoma and its components have drawn extensive attention toward their anti-tumor related diseases. Besides, Coptidis Rhizoma is traditionally used as an anti-inflammatory herb. Epiberberine (EPI) is a significant alkaloid isolated from Coptidis Rhizoma, and exhibits multiple pharmacological activities including anti-inflammatory. However, the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis has not been demonstrated clearly. AIM OF THE STUDY: Bone metastatic breast cancer can lead to osteolysis via inflammatory factors-induced osteoclast differentiation and function. In this study, we try to analyze the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis. METHODS: To evaluate whether epiberberine could suppress bone metastatic breast cancer-induced osteolytic damage, healthy female Balb/c mice were intratibially injected with murine triple-negative breast cancer 4T1 cells. Then, we examined the inhibitory effect and underlying mechanism of epiberberine on breast cancer-induced osteoclastogenesis in vitro. Xenograft assay was used to study the effect of epiberberine on breast cancer cells in vivo. Moreover, we also studied the inhibitory effects and underlying mechanisms of epiberberine on RANKL-induced osteoclast differentiation and function in vitro. RESULTS: The results show that epiberberine displayed potential therapeutic effects on breast cancer-induced osteolytic damage. Besides, our results show that epiberberine inhibited breast cancer cells-induced osteoclast differentiation and function by inhibiting secreted inflammatory cytokines such as IL-8. Importantly, we found that epiberberine directly inhibited RANKL-induced differentiation and function of osteoclast without cytotoxicity. Mechanistically, epiberberine inhibited RANKL-induced osteoclastogensis via Akt/c-Fos signaling pathway. Furthermore, epiberberine combined with docetaxel effectively protected against bone loss induced by metastatic breast cancer cells. CONCLUSIONS: Our findings suggested that epiberberine may be a promising natural compound for treating bone metastatic breast cancer-induced osteolytic damage by inhibiting IL-8 and is worthy of further exploration in preclinical and clinical trials.

Clinical course and factors associated with progressive acro-osteolysis in early systemic sclerosis: a retrospective cohort study.

To examine clinical course of early systemic sclerosis (SSc) and identify factors for progression of acro-osteolysis by a retrospective cohort study. Dual time-point hand radiography was performed at median interval (range 3.0 ± 0.4 years) in 64 recruited patients. Progressive acro-osteolysis was defined as the worsening of severity of acro-osteolysis according to rating scale (normal, mild, moderate, and severe). Incidence of the progression was determined. Cox regression was analyzed for the predictors. A total of 193.6 per 100 person-years, 19/64 patients had progressive acro-osteolysis with incidence of 9.8 per 100-person-years (95% CI 6.3-15.4). The median time of progressive acro-osteolysis was 3.5 years. Rate of progression increased from 1st to 3rd years follow-up with the progression rate at 1-, 2- and 3-years were 0, 2.0 and 18.3%, respectively. Patients with positive anti-topoisomerase I tended to have more progressive acro-osteolysis but no significant predictors on Cox regression. 44%, 18%, and 33% of who had no, mild, and moderate acro-osteolysis previously developed progression and 10 turned to be severe acro-osteolysis. In conclusion, the incidence of progressive acro-osteolysis was uncommon in early SSc but the rate of progression was pronouncedly increasing after three years follow-up. A half of the patients progressed to severe acro-osteolysis.

Case report: BCR-ABL-positive acute lymphoblastic leukemia with bone destruction: a treatment dilemma.

Although bone destruction and hypercalcemia without acute peripheral blast BCR-ABL-positive acute lymphoblastic leukemia (ALL) have been reported in children, they are rare in adults. Herein, we describe a case of BCR-ABL positive ALL with a triploid karyotype, WT1, and CDKN2A mutations with hypercalcemia and bone destruction as the first manifestations. Complete remission (CR) was achieved by induction chemotherapy. BCR-ABL turned negative after treatment with dasatinib. However, computed tomography and whole-body bone scan showed extensive bone destruction. Additionally, bone biopsy showed leukemic infiltration. After treatment with dasatinib and VMCP, leukemia recurred with positive BCR-ABL. The T315I mutation occurred. The patient was surgically diagnosed with calculous cholecystitis and achieved CR2 by postoperative orebatinib and VP regimens. Later, the patient died due to a severe pulmonary infection. BCR-ABL-positive ALL with bone destruction is rare and difficult to control using tyrosine kinase inhibitor chemotherapy alone. Therefore, further exploration of more effective treatments is needed.

Multicentric carpotarsal osteolysis syndrome with variants of MAFB gene: a case report and literature review.

BACKGROUND: Multicentric carpotarsal osteolysis (MCTO) is a rare genetic disorder characterized by the progressive loss of bone in the hands, feet, and other skeletal structures. It presents with symptoms that may resemble those of juvenile idiopathic arthritis, making diagnosis challenging for clinicians. The identification of MAF BZIP Transcription Factor B (MAFB) mutations as significant contributors to MCTO represents a major breakthrough in our understanding of the pathogenesis of this rare skeletal disorder. CASE PRESENTATION: Our objective was to present the phenotype, treatment, and outcome of a patient with a variant of MAFB-induced MCTO to broaden the range of clinical features associated with MCTO and share our clinical experience for improved diagnosis and treatment. In our case, early MRI examination of the bones and whole exome sequencing enabled an early and accurate MCTO diagnosis, and timely Denosumab administration resulted in no deterioration. CONCLUSION: This suggests that MRI examination and whole exome sequencing should be considered when MCTO is suspected, and Denosumab might be an option in the treatment of MCTO.

Deciphering the enigmatic symptoms of Pancoast tumors: Navigating the complex landscape of pain management-A case report.

Pancoast tumors, also known as superior sulcus tumors, encompass a diverse spectrum of neoplasms that infiltrate the apex of the chest wall, yielding distinctive clinical presentations. One of the earliest signs of tumor growth is pain radiating to the upper limb, stemming from peripheral nerve involvement, which can mimic joint pain or spinal radicular irritation. In this case report, we present the clinical history of a 64-year-old female smoker who had previously been recommended for orthopedic elbow surgery due to epicondylitis. Subsequent to the development of additional symptoms and rigorous investigation, a Pancoast tumor was diagnosed. Furthermore, we discuss the characteristic treatment modalities available for Pancoast tumors, including pharmacological pain management and interventional strategies such as spinal cordotomy and spinal alcoholysis. This case underscores the significance of recognizing atypical presentations and emphasizes the importance of comprehensive evaluation in the diagnosis and management of Pancoast tumors.

Nanoparticulate bioceramic putty suppresses osteoclastogenesis and inflammatory bone loss in mice via inhibition of TRAF6-mediated signalling pathways: A laboratory investigation.

AIM: This study aimed to determine the effects of iRoot BP Plus on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and inflammation-mediated bone resorption in vivo and investigated the underlying molecular mechanisms. METHODOLOGY: CCK-8 was performed to test cell viability in RANKL-induced RAW 264.7 cells and BMDMs in response to iRoot BP Plus. The effect of iRoot BP Plus on osteoclastogenesis was determined using TRAP staining and phalloidin staining, respectively. Pit formation assay was conducted to measure osteoclast resorptive capacity. Western blot and qPCR were performed to examine osteoclast-related proteins and gene expression, respectively. Western blot was also used to investigate the signalling pathways involved. For in vivo experiments, an LPS-induced mouse calvarial bone resorption model was established to analyse the effect of iRoot BP Plus on bone resorption (n = 6 per group). At 7 days, mouse calvaria were collected and prepared for histological analysis. RESULTS: We identified that iRoot BP Plus extracts significantly attenuated RANKL-induced osteoclastogenesis, reduced sealing zone formation, restrained osteolytic capacity and decreased osteoclast-specific gene expression (p < .01). Mechanistically, iRoot BP Plus extracts reduced TRAF6 via proteasomal degradation, then suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), blocked the nuclear translocation of c-Fos and diminished nuclear factor-κB (NF-κB) p65 and NFATc1 accumulation. Consistent with the in vitro results, iRoot BP Plus extracts attenuated osteoclast activity thus protecting against inflammatory bone resorption in vivo (p < .05), which was accompanied by a suppression of TRAF6, c-Fos, NFATc1 and cathepsin K expression. CONCLUSION: These findings provide valuable insights into the signalling mechanisms underlying nanoparticulate bioceramic putty-mediated bone homeostasis.