Global scientific trends on exosomes therapy for osteoporosis from 2004 to 2023: A bibliometric and visualized analysis.

BACKGROUND: Exosomes have emerged as pivotal mediators in modulating physiological and pathological processes implicated in osteoporosis (OP) through their distinctive mode of intracellular communication. The use of exosomes has evoked considerable interest, catalyzing a surge in research endeavors on a global scale. This study endeavors to scrutinize contemporary landscapes and burgeoning trends in this realm. METHODS: The Web of Science Core Collection was used to retrieve publications on exosomes therapy for OP within the time frame of January 1, 2004 to December 31, 2023. The bibliometric methodology was applied to study and index the collected data. VOSviewer and citespace software were used to conduct visualization, co-authorship, co-occurrence, and publication trend analyses of exosome therapy in OP. RESULTS: A total of 610 publications (443 articles and 167 reviews) from 51 countries and 911 institutions were included in this study. Shanghai Jiao Tong University, Central South University, Sichuan University, and Zhejiang University are leading research institutions in this field. Stem Cell Research Therapy published the highest number of articles and has emerged as the most cited journal. Of the 4077 scholars who participated in the study, Xie, Hui, Zhang, Yan, Tan, and Yi-Juan had the largest number of articles. Furthermore, according to the cluster analysis of external keywords, future research hotspots can be categorized into 3 directions: research status of exosomes for the treatment of OP, treatment of OP through exosome-regulated signaling pathways, and exosomes as targeted drug delivery systems. CONCLUSION: This study suggests that the number of future publications on exosome therapy for OP will increase, with a focus on fundamental investigations into drug-loading capacities and molecular mechanisms. In summary, this study presents the first systematic bibliometric analysis of exosome therapy publications in OP, providing an objective and comprehensive overview of the field and a valuable reference for researchers in this domain.

Juan-tong-yin potentially impacts endometriosis pathophysiology by enhancing autophagy of endometrial stromal cells via unfolded protein reaction-triggered endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMs) is characterized by inflammatory lesions, dysmenorrhea, infertility, and chronic pelvic pain. Single-target medications often fail to provide systemic therapeutic results owing to the complex mechanism underlying endometriosis. Although traditional Chinese medicines-such as Juan-Tong-Yin (JTY)-have shown promising results, their mechanisms of action remain largely unknown. AIM OF THE STUDY: To elucidate the therapeutic mechanism of JTY in EMs, focusing on endoplasmic reticulum (ER) stress-induced autophagy. MATERIALS AND METHODS: The major components of JTY were detected using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The potential mechanism of JTY in EMs treatment was predicted using network pharmacological analysis. Finally, the pathogenesis of EMs was validated in a clinical case-control study and the molecular mechanism of JTY was validated in vitro using endometrial stromal cells (ESCs). RESULTS: In total, 241 compounds were analyzed and identified from JTY using UPLC-MS. Network pharmacology revealed 288 targets between the JTY components and EMs. Results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that regulating autophagy, migration, apoptosis, and inflammation were the key mechanisms of JTY in treating EMs. Meanwhile, we found that protein kinase R-like endoplasmic reticulum kinase (PERK), Beclin-1, and microtubule-associated protein light chain 3 B (LC3B) expressions were lower in endometria of patients with EMs than in those with normal eutopic endometria (p < 0.05). Additionally, during in vitro experiments, treatment with 20% JTY-containing serum significantly suppressed ESC proliferation, achieving optimal effects after 48 h. Electron microscopy revealed significantly increased autophagy flux in the JTY group compared with the control group. Moreover, JTY treatment significantly reduced the migratory and invasive abilities of ESCs and upregulated protein expression of PERK, eukaryotic initiation factor 2α (eIF2α)/phospho-eukaryotic initiation factor 2α (p-eIF2α), activating Transcription Factor-4 (ATF4), Beclin-1, and LC3BII/I, while subsequently downregulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin 18 (IL-18) expression. However, administration of GSK2656157-a highly selective PERK inhibitor-reversed these changes. CONCLUSION: JTY ameliorates EMs by activating PERK associated with unfolded protein reaction, enhancing cell ER stress and autophagy, improving the inflammatory microenvironment, and decreasing the migration and invasion of ESCs.

Lung adenocarcinoma with brain metastasis detected dual fusion of LOC399815-ALK and ALK-EML4 in combined treatment of Alectinib and CyberKnife: A case report.

INTRODUCTION: The anaplastic lymphoma kinase (ALK) gene fusion occurs in approximately 3% to 7% of nonsmall cell lung cancer (NSCLC), in which occurs approximately 23% to 31% of brain metastasis patients in poor prognosis. ALK tyrosine kinase inhibitors have shown efficacy in treating ALK-positive (ALK+) NSCLC. More than 90 distinct subtypes of ALK fusions have been identified through sequencing technique and would lead to significant differences in clinical efficacy, it is necessary to guide clinical treatment effectively by gene detection. PATIENT CONCERNS: A 56-year-old nonsmoking female admitted to hospital due to cough, expectoration, and chest pain. Chest computed tomography revealed a space-occupying lesion in the upper left lobe (5.0 cm × 2.4 cm × 2.9 cm), multiple enlarged lymph nodes in mediastinum 3A and 5 (largest size 1.5 cm × 1.4 cm), and evidence of thoracic vertebral metastasis, brain magnetic resonance imaging also showed brain metastasis. DIAGNOSES: Lung adenocarcinoma with brain metastasis. INTERVENTIONS: The patient initially received conventional first-line chemotherapy, which led to a deteriorated condition. Blood-base liquid biopsy by next-generation sequencing resulted in double ALK fusions, in which with a neo-partner of lncRNA (LOC399815-ALK). Following subsequent treatment with Alectinib and stereotactic radiotherapy (CyberKnife) was subsequently employed to manage the brain metastatic lesions, resulting in a substantial decreased in both the number and size of tumor lesions. OUTCOMES: The patient's response to therapy efficacy resulted in a substantial decreased in both the number and size of tumor lesions that assessed comprehensively evaluated through computed tomography imaging and ctDNA sequencing. Patient's condition has been under control for over 29 months. CONCLUSION: Liquid biopsy may reveal the rare fusion forms of ALK, precisely guiding personalized treatment, and providing a reference method for longitudinal monitoring and efficacy evaluation of ALK-tyrosine kinase inhibitors in NSCLC patients.

A machine learning-based model for clinical prediction of distal metastasis in chondrosarcoma: a multicenter, retrospective study.

Background: The occurrence of distant metastases (DM) limits the overall survival (OS) of patients with chondrosarcoma (CS). Early diagnosis and treatment of CS remains a great challenge in clinical practice. The aim of this study was to investigate metastatic factors and develop a risk stratification model for clinicians' decision-making. Methods: Six machine learning (ML) algorithms, including logistic regression (LR), plain Bayesian classifier (NBC), decision tree (DT), random forest (RF), gradient boosting machine (GBM) and extreme gradient boosting (XGBoost). A 10-fold cross-validation was performed for each model separately, multicenter data was used as external validation, and the best (highest AUC) model was selected to build the network calculator. Results: A total of 1,385 patients met the inclusion criteria, including 82 (5.9%) patients with metastatic CS. Multivariate logistic regression analysis showed that the risk of DM was significantly higher in patients with higher pathologic grades, T-stage, N-stage, and non-left primary lesions, as well as those who did not receive surgery and chemotherapy. The AUC of the six ML algorithms for predicting DM ranged from 0.911-0.985, with the extreme gradient enhancement algorithm (XGBoost) having the highest AUC. Therefore, we used the XGB model and uploaded the results to an online risk calculator for estimating DM risk. Conclusions: In this study, combined with adequate SEER case database and external validation with data from multicenter institutions in different geographic regions, we confirmed that CS, T, N, laterality, and grading of surgery and chemotherapy were independent risk factors for DM. Based on the easily available clinical risk factors, machine learning algorithms built the XGB model that predicts the best outcome for DM. An online risk calculator helps simplify the patient assessment process and provides decision guidance for precision medicine and long-term cancer surveillance, which contributes to the interpretability of the model.

Small noncoding RNA dysregulation is implicated in manganism in a rat model of methylcyclopentadienyl manganese tricarbonyl-induced unrepaired striatum damage.

The accumulation of excessively high manganese levels within the brain can contribute to a series of Parkinsonian symptoms referred to as manganism. The gasoline antiknock additive Methylcyclopentadienyl Manganese Tricarbonyl (MMT) is an environmental source of manganese exposure and can induce manganism in rats. While some prior reports have demonstrated the differential expression of small noncoding RNAs (sncRNAs) in patients with Parkinson's disease (PD), the degree of sncRNA dysfunction in manganism has yet to be clearly documented. As sncRNAs such as transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs) exhibit high levels of modifications such as 3' terminal 3'-phosphate and 2',3'-cyclic phosphate modifications that disrupt the process of adapter ligation and m1A, m3C, m1G, and m22G RNA methylation, these transcripts are not detected in traditional small RNA-sequencing studies. Here, differential sncRNA expression was analyzed by comparing a rat model of MMT-induced unrepaired striatum damage to appropriate control samples via PANDORA-Seq, which can detect highly modified sncRNAs. Following the removal of sncRNA modifications, this approach identified 599 sncRNAs that were differentially expressed in the striatum of MMT-exposed rats relative to controls, as well as 1155 sncRNAs that were differentially expressed in Mn-treated and control rats. Additional functional analyses were performed to predict the putative targets of these sncRNAs, implicating a role for such sncRNA dysregulation in the pathogenesis of manganism in this rat model system.

ERß compensates for the absence of ERα function to promote osteoblast viability by inhibition of SOST signaling.

Estrogen receptors α and ß (ERα and ERß) serve key functions in bone development and maintenance, and in the metabolism of bone mineral. ERß and ERα form heterodimers, and ERß negatively regulates the transactivation of ERα. ERß also inhibits recruitment of ERα to the estrogen-responsive promoters. However, the relationship of ERα and ERß in the regulation of osteoblast viability and differentiation remains unclear. The present study aimed to investigate whether ERß plays a role in balancing ERα activity in osteoblast cells. Downregulation of ERα by short hairpin RNA (shRNA) was found to significantly increase cell cycle arrest at G1 phase (P<0.01). In addition, this effect was found to be significantly enhanced by downregulation of ERß (P<0.05). Inversely, ERα-knocked down osteoblasts were treated with ERß agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) to activate ERß. It was found that activation of ERß significantly rescued the arrest of cell cycle induced by the downregulation of ERα (P<0.05). Furthermore, downregulation of ERα was found to significantly inhibit cell viability (P<0.01), and knockdown of ERß was found to have a significant synergic effect with ERα downregulation on the inhibition of cell viability (P<0.01). Treatment with ERß agonist DPN significantly rescued the effects of downregulation of ERα on cell viability (P<0.01). It was also demonstrated that the synergic effects of ERα and ERß deletion was via upregulation of SOST gene expression, and the subsequent inhibition of OPG and Runx2 gene expression. Thus, ERß may serve a function in balancing osteoblast viability and differentiation induced by ERα.

Matrine inhibits IL-1ß-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro.

Interleukin (IL)-1ß plays an important role in promoting osteoarthritis (OA) lesions by inducing chondrocytes to secrete matrix metalloproteinases (MMPs), which degrade the extracellular matrix and facilitate chondrocyte apoptosis. Matrine was shown to exert anti-inflammatory effects. However, the role of matrine in OA is still unclear. Therefore, in this study, we investigated the effects of matrine on the expression of MMPs in IL-1ß-treated human chondrocytes and the underlying mechanism. The cell viability of chondrocytes was detected by MTT assay. The cell apoptosis of chondrocytes was measured by flow cytometric analysis. The protein production of MMPs was determined by ELISA. The protein expression of phosphorylation of mitogen-activated protein kinases (MAPKs) and the inhibitor of kappaB alpha (IκBα) was determined by Western blot. Matrine significantly inhibited the IL-1ß-induced apoptosis in chondrocytes. It also significantly inhibited the IL-1ß-induced release of MMP-3 and MMP-13, and increased the production of TIMP-1. Furthermore, matrine inhibits the phosphorylation of p-38, extracellular regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and IκBα degradation induced by IL-1ß in chondrocytes. Taken together, our results show that matrine inhibits IL-1ß-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro. Therefore,-matrine may be beneficial in the treatment of OA.

Preparation and application of collagen scaffold-encapsulated silver nanoparticles and bone morphogenetic protein 2 for enhancing the repair of infected bone.

The healing of contaminated/infected bone defects is a significant clinical challenge. Here, a novel collagen scaffold composite encapsulating silver nanoparticles (AgNP) and bone morphogenetic protein 2 (BMP-2) was prepared to enhance the healing of infected bone defects. Collagen scaffolds conjugated with AgNP possessed strong antibacterial properties that were dependent on the release rate of Ag(+). After introducing BMP-2, the BMP-2/AgNP/collagen scaffold composites did not adversely affect the adherence or proliferation of bone marrow-derived mesenchymal stromal cells (BMSCs). Differentiation of BMSCs toward osteoblasts was induced by the upregulation of RUNX2, osteopontin and osteonectin expression. BMP-2/AgNP/collagen scaffold composites, therefore, possess the antibacterial activity of AgNP and the osteoinductivity of BMP-2, making these composites an ideal pharmaceutical for the regeneration of bone in infected wounds.

Monocyte chemotactic protein-1 -2518 gene polymorphism and susceptibility to spinal tuberculosis.

BACKGROUND AND AIMS: Monocyte chemotactic protein-1 (MCP-1) gene polymorphisms play important roles in regulating immunological reactions and may be associated with pulmonary tuberculosis. However, the relationship between the MCP-1 -2518 gene polymorphism and susceptibility to spinal tuberculosis remains unknown. We undertook this study to investigate the relationships between MCP-1 promoter 2518 genotype frequency and allele polymorphisms and susceptibility to spinal tuberculosis in a Chinese Han population. METHODS: Patients with spinal tuberculosis and healthy volunteers were enrolled between December 2004 and December 2010. MCP-1 -2518 polymorphisms in both groups were detected using polymerase chain reaction and DNA sequencing. MCP-1 genotype was analyzed in all patients. Differences in genotype frequencies between groups were compared using χ(2) tests. RESULTS: A total of 208 patients with spinal tuberculosis and 210 healthy volunteers were included. The distribution frequencies of MCP-1 -2518 GG, GA and AA genotypes were 36.1, 50.9 and 13.0%, respectively, in the case group and 25.2, 53.8 and 21.0%, respectively, in the control group (p <0.05). MCP-1 -2518 GG genotype was significantly associated with the onset of spinal tuberculosis (OR = 2.306, 95% CI = 1.273-4.178). The G and A allele frequencies were 61.5% and 38.5%, respectively, in the case group, and 52.1% and 47.9% in the control group (p <0.05), the allele "G" of MCP-1 -2518 showed an association with an increased risk for spinal tuberculosis: OR = 1.777, 95% CI = 1.053-2999, p = 0.03 in the dominant model; OR = 1.67, 95% CI = 1.097-2.544, p = 0.016 in the recessive model. CONCLUSIONS: The MCP-1 -2518 GG genotype and presence of the G allele may be associated with susceptibility to spinal tuberculosis in the Chinese Han population.

Monocyte chemoattractant protein-1 in spinal tuberculosis: -362G/C genetic variant and protein levels in Chinese patients.

The objective of the study is to explore the possible association of the monocyte chemoattractant protein (MCP)-1-362G/C genetic polymorphism and plasma levels of MCP-1 in patients with spinal tuberculosis (TB). The MCP-1-362G/C (rs2857656) polymorphism and blood levels of MCP-1 in patients with spinal TB and healthy subjects were evaluated and compared. Three hundred thirty-two patients and 336 healthy subjects were genotyped using polymerase chain reaction and Sanger DNA sequencing technology. MCP-1 plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. When comparisons were made between patients and controls, the frequency of the MCP-1-362*C minor allele (55.4% versus 47.5%, P = 0.004, odds ratio [OR] = 1.376, 95% confidence interval [CI]: 1.109-1.706) and the carriers of the MCP-1-362*C allele (80.7% versus 71.4%, P = 0.005, OR = 1. 657, 95% CI: 1.167-2.403) were over-represented in patients. The mean MCP-1 plasma level in spinal TB patients was significantly higher than in controls (154.44 ± 68.81 pg/mL versus 36.69 ± 21.71 pg/mL, t = -5.85, P < 0.001). The patients with the CC genotype had the highest MCP-1 level (150.63 ± 73.89 pg/mL), followed by those with the GC genotype (108.63 ± 52.09 pg/mL, t = 2.351, P = 0.022) and GG (91.29 ± 54.31 pg/mL, t = 3.091, P = 0.003) homozygotes. We report the association of the -362G/C genetic polymorphism and increased plasma levels of MCP-1 in patients with spinal TB and nominate the -362*C minor allele as a risk factor for spinal TB in the Chinese population.

Strong halo-femoral traction with wide posterior spinal release and three dimensional spinal correction for the treatment of severe adolescent idiopathic scoliosis.

BACKGROUND: Many investigators advocate anterior release combined with halo-femoral traction and posterior fusion when treating stiff thoracic curves in patient with adolescent idiopathic scoliosis (AIS). But the anterior operations often induce severe complications. Some surgeons choose posterior-only surgery with halo-femoral traction, posterior wide release and correction. But to the best of our knowledge, there are only rare prospective studies on these posterior-only surgeries for AIS patients who have a rigid curve more than 80° and flexibility less than 35%. METHODS: Sixty-four AIS patients were recruited from September 2006 to June 2009. All patients had rigid curves and underwent spinal correction. They were randomly divided into group A (combined anteroposterior surgery) and group B (posterior-only surgery). Images and scoliosis research society-22 questionnaire (SRS-22) scores were performed pre- and post-operation and during follow-up visits. The operation time, blood loss, hospital days, and hospital charges were compared between the two groups. RESULTS: These patients were followed for an average of 37.5 months (range, 24 - 65 months). No serious complications were observed. There were no significant differences between the two groups in gender, age, preoperative radiographic data, or preoperative SRS-22 score. The average operation time, blood loss, hospital days and hospital charges in group B were less than those in group A. The SRS-22 score in group B was better than in group A at post-operation and at final follow-up. CONCLUSIONS: In AIS with a rigid curve more than 80° and flexibility less than 35%, strong halo-femoral traction with wide posterior spinal release and three dimensional spinal correction can provide better SRS-22 scores, comparable curve correction, shorter operation time, less blood loss, shorter hospital stays and lower charges when compared to combined anterior and posterior surgery.

Clinical evaluation of indirect decompression treatments for degenerative adult idiopathic scoliosis.

STUDY DESIGN: Prospective case series. OBJECTIVE: Degenerative idiopathic scoliosis can be a cause of back pain. We sought to explore the feasibility and effectiveness of indirect decompression treatment in posterior correction and fusion for adult idiopathic scoliosis patients with radiculopathy and combined lateral olisthesis and/or foraminal stenosis. METHODS: Thirty seven degenerative adult idiopathic scoliosis patients with radiculopathy were recruited. Prostration or body traction alleviated the neurological deficit in these patients. Their symptoms were aggravated, when patients stood up. Imaging was used to assess lateral olisthesis and/or foraminal stenosis. All patients underwent posterior pedicle screw fixation, deformity correction, dorsal lamina and posterolateral bone grafting with the indirect decompression treatment. Clinical examinations including visual analog scale (VAS), oswestry disability index (ODI) scores, and images were performed pre- and post-operation and during follow-up visits. RESULTS: Twenty seven patients were followed for the average of 30.8 months. No serious complication was observed. The cobb's angle, lateral olisthesis, thoracic kyphosis, thoracolumbar kyphosis, lumbar lordosis, VAS and ODI scores, coronal and sagittal balance were significantly improved among the patients who underwent the indirect decompression treatment. All patients had eliminated neurological deficit at their final follow-ups. CONCLUSIONS: The indirect decompression treatment in the posterior correction and fusion can be effective for adult idiopathic scoliosis patients with radiculopathy and combined lateral olisthesis and/or foraminal stenosis. This indicates the premise of strict operation indication.

Association of estrogen receptor beta gene polymorphisms with susceptibility to adolescent idiopathic scoliosis.

STUDY DESIGN: A case-control study is presented. OBJECTIVE: To investigate the association of estrogen receptor beta gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Studies have shown that idiopathic scoliosis is related to genetic factors, such as XbaI site polymorphism of the estrogen receptor alpha gene. To our knowledge, however, the relationship of estrogen receptor beta gene polymorphisms and the individual susceptibility to idiopathic scoliosis has not been studied. METHODS: This study included 218 patients with AIS and 140 healthy controls. Height, menarche status, curve pattern, Cobb angle, and Risser sign in female patients were recorded. Blood samples were taken from each subject by venipuncture. Genomic DNA was extracted from peripheral blood leukocytes using standard phenol/chloroform extraction. PCR products from amplification of genomic DNA from all individuals were analyzed using denaturing high-performance liquid chromatography. Samples with aberrant HPLC profiles were sequenced in both the forward and the reverse directions on an ABI 3100 automated sequencer. The chi test was used to determine the significant difference in genotype distribution between patients with AIS and the controls. RESULTS: The frequency of CC genotype of the exon ØK (in reality 5' UTR OK-1)was significantly higher in patients than that in controls (P < 0.05). The C alleles appeared to be overrepresented in patients compared with controls (P < 0.05). Furthermore, the frequencies of CC genotypes in female patients whose height was > or =160 cm and Cobb angle was > or =30 degrees were higher than those whose height was <160 cm and Cobb angle was <30 degrees (P < 0.05). CONCLUSION.: The sites of the exon ØK polymorphisms of estrogen receptor beta gene may be associated with a susceptibility of AIS. Furthermore, the sites of the exon ØK polymorphism may be associated with the height and the curve severity of patients.