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Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis (AS),...
OBJECTIVE
To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis (AS), to unveil their potential involvement in the pathogenesis of AS, and to provide new strategies and targets for the clinical treatment of AS by analyzing the methylation state of H3K27me3 and its interactions with Th17-related factors.
METHODS
A total of 84 AS patients (42 active AS patiens and 42 patients in the stable phase of AS) were enrolled for the study, while 84 healthy volunteers were enrolled as the controls. Blood samples were collected. Peripheral blood mononuclear cells were isolated. ELISA assay was performed to examine Th17 cells and the relevant cytokines IL-21, IL-22, and IL-17. The mRNA expressions of , , and were analyzed by RT-PCR, the protein expressions of RORc, JAK2/STAT3 pathway protein, H3K27me3 and the relevant protease (EZH2 and JMJD3) were determined by Western blot. Correlation between H3K27me3, EZH2 and JMJD3 and the key signaling pathway molecules of Th cell differentiation was analyzed by Pearson correlation analysis.
RESULTS
The mRNA expressions of , , and were significantly higher in the active phase group than those in the stable phase group ( <0.05). The relative grayscale values of H3K27me3 and EZH2 in the active phase group were lower than those of the stable phase group, which were lower than those of the control group, with the differences being statistically significant ( <0.05). The relative grayscale values of JMJD3, RORc, JAK2, pJAK2, STAT3, and pSTAT3 proteins were significantly higher in the active phase group than those in the stable phase group, which were higher than those in the control group (all <0.05). The proportion of Th17 and the expression level of inflammatory factors in the active period group were higher than those in the other two groups (P<0.05). H3K27me3 was negatively correlated with RORc, JAK2, STAT3, and IL-17, JMJD3 was positvely correlated with JAK2, STAT3, and IL-17, and EZH2 was negatively correlated with JAK2, STAT3, and IL-17 (all <0.05).
CONCLUSION
The low expression of H3K27me3 in AS is influenced by the gene loci JMJD3 and EZH2, which can regulate the differentiation of Th17 cells and thus play a role in the pathogenesis and progression of AS.
Topics: Humans; Spondylitis, Ankylosing; Th17 Cells; Jumonji Domain-Containing Histone Demethylases; Cell Differentiation; Histones; STAT3 Transcription Factor; Enhancer of Zeste Homolog 2 Protein; Epigenesis, Genetic; Interleukin-17; Nuclear Receptor Subfamily 1, Group F, Member 3; Janus Kinase 2; Methylation; Interleukins; Interleukin-22; Male; Female; Adult
PubMed: 38948276
DOI: 10.12182/20240560605 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA).
OBJECTIVE
To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA).
METHODS
A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women.
RESULT
A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-β2 glycoprotein Ⅰ antibodies (β2GPⅠ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both β2GPⅠ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both β2GPⅠ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies.
CONCLUSION
Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.
Topics: Humans; Female; Adult; Abortion, Habitual; Retrospective Studies; Pregnancy; Autoantibodies; Maternal Age; Immunity, Humoral; Middle Aged; Antiphospholipid Syndrome; China; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Young Adult; Antibodies, Antinuclear; Arthritis, Rheumatoid; Undifferentiated Connective Tissue Diseases; Antibodies, Antiphospholipid; Logistic Models
PubMed: 38948271
DOI: 10.12182/20240560506 -
PeerJ 2024The methods previously proposed in the literature to assess patients with rotator cuff related shoulder pain, based on special orthopedic tests to precisely identify the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The methods previously proposed in the literature to assess patients with rotator cuff related shoulder pain, based on special orthopedic tests to precisely identify the structure causing the shoulder symptoms have been recently challenged. This opens the possibility of a different way of physical examination.
OBJECTIVE
To analyze the differences in shoulder range of motion, strength and thoracic kyphosis between rotator cuff related shoulder pain patients and an asymptomatic group.
METHOD
The protocol of the present research was registered in the International Prospective Register of Systematic Review (PROSPERO) (registration number CRD42021258924). Database search of observational studies was conducted in MEDLINE, EMBASE, WOS and CINHAL until July 2023, which assessed shoulder or neck neuro-musculoskeletal non-invasive physical examination compared to an asymptomatic group. Two investigators assessed eligibility and study quality. The Newcastle Ottawa Scale was used to evaluate the methodology quality.
RESULTS
Eight studies ( = 604) were selected for the quantitative analysis. Meta-analysis showed statistical differences with large effect for shoulder flexion (I2 = 91.7%, < 0.01, HG = -1.30), external rotation (I2 = 83.2%, < 0.01, HG = -1.16) and internal rotation range of motion (I2 = 0%, < 0.01, HG = -1.32). Regarding to shoulder strength; only internal rotation strength showed statistical differences with small effect (I2 = 42.8%, < 0.05, HG = -0.3).
CONCLUSIONS
There is moderate to strong evidence that patients with rotator cuff related shoulder pain present less shoulder flexion, internal and external rotation range of motion and less internal rotation strength than asymptomatic individuals.
Topics: Humans; Range of Motion, Articular; Shoulder Pain; Rotator Cuff; Muscle Strength; Rotator Cuff Injuries; Shoulder Joint; Kyphosis
PubMed: 38948223
DOI: 10.7717/peerj.17604 -
PeerJ 2024Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with systemic implications, potentially affecting musculoskeletal health. This study aimed to assess...
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with systemic implications, potentially affecting musculoskeletal health. This study aimed to assess shoulder muscle strength and joint repositioning accuracy in individuals with T2DM, exploring potential correlations and shedding light on the musculoskeletal consequences of the condition. The objectives were two-fold: (1) to assess and compare shoulder strength and joint repositioning accuracy between individuals with T2DM and asymptomatic counterparts, and (2) to examine the correlation between shoulder strength and joint repositioning accuracy in individuals with T2DM.
METHODS
A cross-sectional study enrolled 172 participants using the convenience sampling method, including 86 individuals with T2DM and an age-matched asymptomatic group ( = 86). Shoulder strength was assessed using a handheld dynamometer, while joint repositioning accuracy was evaluated with an electronic digital inclinometer.
RESULTS
Individuals with T2DM exhibited reduced shoulder muscle strength compared to asymptomatic individuals ( < 0.001). Additionally, joint repositioning accuracy was significantly lower in the T2DM group ( < 0.001). Negative correlations were observed between shoulder strength and joint repositioning accuracy in various directions (ranging from -0.29 to -0.46, < 0.001), indicating that higher muscle strength was associated with improved joint repositioning accuracy in individuals with T2DM.
CONCLUSION
This study highlights the significant impact of T2DM on shoulder muscle strength and joint repositioning accuracy. Reduced strength and impaired accuracy are evident in individuals with T2DM, emphasizing the importance of addressing musculoskeletal aspects in diabetes management. The negative correlations suggest that enhancing shoulder muscle strength may lead to improved joint repositioning accuracy, potentially contributing to enhanced physical functioning in this population.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Cross-Sectional Studies; Female; Middle Aged; Muscle Weakness; Muscle Strength; Shoulder; Proprioception; Shoulder Joint; Aged; Adult; Range of Motion, Articular
PubMed: 38948217
DOI: 10.7717/peerj.17630 -
Theranostics 2024Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs...
Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs undergo apoptosis shortly after transplantation and produce apoptotic extracellular vesicles (ApoEVs). This study aims to clarify the potential role of ApoEVs from apoptotic MSCs in ameliorating osteoporosis and molecular mechanism. In this study, Dio-labeled bone marrow mesenchymal stem cells (BMSCs) were injected into mice to track BMSCs apoptosis and ApoEVs production. ApoEVs were isolated from BMSCs after inducing apoptosis, the morphology, size distribution, marker proteins expression of ApoEVs were characterized. Protein mass spectrometry analysis revealed functional differences in proteins between ApoEVs and BMSCs. BMSCs were adopted to test the cellular response to ApoEVs. Ovariectomy mice were used to further compare the ability of ApoEVs in promoting bone formation. SiRNA and lentivirus were used for gain and loss-of-function assay. The results showed that BMSCs underwent apoptosis within 2 days after being injected into mice and produce a substantial quantity of ApoEVs. Proteomic analysis revealed that ApoEVs carried a diverse functional array of proteins, and easily traversed the circulation to reach the bone. After being phagocytized by endogenous BMSCs, ApoEVs efficiently promoted the proliferation, migration, and osteogenic differentiation of BMSCs. In an osteoporosis mouse model, treatment of ApoEVs alleviated bone loss and promoted bone formation. Mechanistically, ApoEVs carried Ras protein and activated the Ras/Raf1/Mek/Erk pathway to promote osteogenesis and bone formation and . Given that BMSC-derived ApoEVs are high-yield and easily obtained, our data underscore the substantive role of ApoEVs from dying BMSCs to treat bone loss, presenting broad implications for cell-free therapeutic modalities.
Topics: Animals; Extracellular Vesicles; Mesenchymal Stem Cells; Osteoporosis; Apoptosis; Mice; Female; Osteogenesis; Cell Differentiation; Mesenchymal Stem Cell Transplantation; Cell Proliferation; Mice, Inbred C57BL; Disease Models, Animal; Ovariectomy; Proteomics; Signal Transduction
PubMed: 38948067
DOI: 10.7150/thno.96174 -
Theranostics 2024The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between...
The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Here, an injectable H-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold to provide mechanical support. With the appropriate release of H and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Overall, our study provides critical insight into the design and development of H-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.
Topics: Animals; Magnesium; Reactive Oxygen Species; Mice; Polyethylene Glycols; Hydrogels; Osteoporosis; Osteogenesis; Hydrogen; RAW 264.7 Cells; Bone Regeneration; Immunomodulation; Tissue Scaffolds; Macrophages; Polyesters
PubMed: 38948054
DOI: 10.7150/thno.97412 -
Oncology Research 2024Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in...
BACKGROUND
Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.
METHODS
In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration.
RESULTS
After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% ( = 0.003) and 2% ( = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable.
CONCLUSIONS
In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.
Topics: Animals; Taurine; Thiadiazines; Osteosarcoma; Mice; Disease Models, Animal; Bone Neoplasms; Tumor Burden; Microvascular Density; Mice, Inbred BALB C; Cell Line, Tumor; Antineoplastic Agents; Angiogenesis Inhibitors; Humans; Neovascularization, Pathologic
PubMed: 38948019
DOI: 10.32604/or.2024.050907 -
Cureus May 2024Psychosomatic medicine has been known to play a pivotal role in the management of complex medical cases by providing a bridge between the physical disease and...
Psychosomatic medicine has been known to play a pivotal role in the management of complex medical cases by providing a bridge between the physical disease and psychological distress. This case study focuses on a 42-year-old Saudi female diagnosed with breast cancer and generalized anxiety disorder. In addition to anxiety, the patient had a history of obsessive-compulsive personality traits, which contributed to her reluctance to undergo mastectomy. Significant challenges and noncompliance with treatment were caused by her unwillingness and inadequate interaction with the medical team. An integrated multidisciplinary strategy including psycho-oncological interventions was necessary because of the complexity of this case. Communication issues were addressed through the concerted efforts of the specialist teams. A comprehensive patient-practitioner understanding was established, which enabled the teams to persuade the patient to undergo surgical intervention. Overcoming her initial resistance, the patient eventually complied with the treatment plan, leading to a successful surgery. Postsurgical evaluations using the Hamilton Anxiety Scale indicated a significant reduction in anxiety levels. This case underscores the critical contribution of psychosomatic medicine to healthcare, especially in challenging situations that demand additional resource allocation, further highlighting the importance of an interdisciplinary approach, efficient communication, and patient-practitioner rapport in healthcare outcomes.
PubMed: 38947634
DOI: 10.7759/cureus.61343 -
Frontiers in Immunology 2024The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.
Topics: Female; Humans; Bilirubin; Biomarkers; Oxidative Stress; Rheumatic Diseases; Male
PubMed: 38947324
DOI: 10.3389/fimmu.2024.1369284 -
Frontiers in Immunology 2024The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed... (Review)
Review
The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.
Topics: Humans; Female; Spondylarthritis; Pregnancy; Fertility; Infertility, Female; Adult; Ovarian Reserve
PubMed: 38947314
DOI: 10.3389/fimmu.2024.1412174