Intervention of inflammation associated with ankylosing spondylitis by triptolide promotes histone H3 Iys-27 trimethylation.

Objective: This study aims to explore the effects of Triptolide (TP) on the differentiation of Th17 cells in ankylosing spondylitis (AS).Methods: Peripheral blood mononuclear cells (PBMCs) collected from 10 patients with active AS patients were exposed to TP, GSK-J4 or vehicle. T lymphocyte subsets were analyzed using flow cytometry. ELISA was used to assess the level of IL-17. Western blot analysis and quantitative RT-PCR were used to measure the mRNA and protein levels of RORγt, JMJD3, EZH2, JAK2 and STAT3 in the JAK2/STAT3 signaling pathway.Results: We observed a tendency toward a greater percentage of IL-17-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with active AS than in those from healthy controls. Triptolide (TP) and GSK-J4 significantly reduced IL-17 expression. In cultured PBMCs from patients with active AS, 24 h of treatment with TP or GSK-J4 decreased the expression of RORγt (p < 0.05), JAK2 and STAT3 (JAK2: p < 0.05; STAT3: p < 0.05). Furthermore, both triptolide and GSK-J4 increased the level of histone 3 with Lys 27 trimethylation (H3K27me3) in patient-derived PBMCs. H3K27me3 enrichment was detected at the promoters of the RORc, STAT3 and IL-17 genes. Consistent with this finding, triptolide upregulated the EZH2 gene and downregulated the JMJD3 gene.Conclusion: Triptolide inhibits Th17 cell differentiation via H3K27me3 upregulation and orchestrates changes in histone-modifying enzymes, including JMJD3 and EZH2. These findings support the clinical efficacy of triptolide for AS and may provide clues for identifying molecular targets for the development of novel treatments.

Characteristics of PD-1+CD4+ T cells in peripheral blood and synovium of rheumatoid arthritis patients.

Objectives: PD-1 plays a crucial role in the immune dysregulation of rheumatoid arthritis (RA), but the specific characteristics of PD-1+CD4+ T cells remain unclear and require further investigation. Methods: Circulating PD-1+CD4+ T cells from RA patients were analysed using flow cytometry. Plasma levels of soluble PD-1 (sPD-1) were measured using enzyme-linked immunosorbent assay (ELISA). Single-cell RNA sequence data from peripheral blood mononuclear cells (PBMCs) and synovial tissue of patients were obtained from the GEO and the ImmPort databases. Bioinformatics analyses were performed in the R studio to characterise PD-1+CD4+ T cells. Expression of CCR7, KLF2 and IL32 in PD-1+CD4+ T cells was validated by flow cytometry. Results: RA patients showed an elevated proportion of PD-1+CD4+ T cells in peripheral blood, along with increased plasma sPD-1 levels, which positively correlated with TNF-α and erythrocyte sedimentation rate. Bioinformatic analysis revealed PD-1 expression on CCR7+CD4+ T cells in PBMCs, and on both CCR7+CD4+ T cells and CXCL13+CD4+ T cells in RA synovium. PD-1 was co-expressed with CCR7, KLF2, and IL32 in peripheral CD4+ T cells. In synovium, PD-1+CCR7+CD4+ T cells had higher expression of TNF and LCP2, while PD-1+CXCL13+CD4+ T cells showed elevated levels of ARID5A and DUSP2. PD-1+CD4+ T cells in synovium also appeared to interact with B cells and fibroblasts through BTLA and TNFSF signalling pathways. Conclusion: This study highlights the increased proportion of PD-1+CD4+ T cells and elevated sPD-1 levels in RA. The transcriptomic profiles and signalling networks of PD-1+CD4+ T cells offer new insights into their role in RA pathogenesis.

Effects of Confined Microenvironments with Protein Coating, Nanotopography, and TGF-ß Inhibitor on Nasopharyngeal Carcinoma Cell Migration through Channels.

Distant metastasis is the primary cause of unsuccessful treatment in nasopharyngeal carcinoma (NPC), suggesting the crucial need to comprehend this process. A tumor related to NPC does not have flat surfaces, but consists of confined microenvironments, proteins, and surface topography. To mimic the complex microenvironment, three-dimensional platforms with microwells and connecting channels were designed and developed with a fibronectin (FN) coating or nanohole topography. The potential of the transforming growth factor-ß (TGF-ß) inhibitor (galunisertib) for treating NPC was also investigated using the proposed platform. Our results demonstrated an increased traversing probability of NPC43 cells through channels with an FN coating, which correlated with enhanced cell motility and dispersion. Conversely, the presence of nanohole topography patterned on the platform bottom and the TGF-ß inhibitor led to a reduced cell traversing probability and decreased cell motility, likely due to the decrease in the F-actin concentration in NPC43 cells. This study highlights the significant impact of confinement levels, surface proteins, nanotopography, and the TGF-ß inhibitor on the metastatic probability of cancer cells, providing valuable insights for the development of novel treatment therapies for NPC. The developed platforms proved to be useful tools for evaluating the metastatic potential of cells and are applicable for drug screening.

Horizontal transmission of a rice bacterial pathogen Pantoea ananatis among plants by rice planthoppers.

Pantoea ananatis is a bacterium commonly found in various agronomic crops and agricultural pests. In this study, we present findings on a genome-reduced strain of P. ananatis, known as Lstr, which was initially isolated from Laodelphax striatellus (small brown rice planthopper, SBPH). We identified Lstr as a plant pathogen causing disease in rice using Koch's postulates. The pathogenicity of Lstr on rice is comparable to that of Xanthomonas oryzae pv. oryzae, the main causative agent of rice bacterial blight. Through a series of experiments involving live insects, molecular investigations, and microscopy, we find that Lstr can accumulate within SBPH. Subsequently, Lstr can be transmitted from SBPH to rice plants, resulting in leaf blight, and can also be transmitted to other SBPH individuals. Collectively, our results suggest that SBPH serves as a vector for P. ananatis Lstr in rice plants. P. ananatis may encounter susceptible insect populations and become endemic through horizontal transmission from these insects. This could also be valuable for predicting future occurrences of bacterial leaf blight in rice and other crops caused by P. ananatis.

Piperazine ferulate inhibits diabetic nephropathy by suppressing AGE/RAGE-mediated inflammatory signaling in rats and podocytes.

Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro, rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro. Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.

Transcriptomic landscapes reveal development-related physiological processes in the two-spotted spider mite, Tetranychus urticae.

The two-spotted spider mite (Tetranychus urticae Koch, TSSM) is recognized as one of the most problematic spider mite pests. However, the precise gene expression patterns across its key developmental stages remain elusive. Here, we performed a comprehensive transcriptome analysis of TSSM eggs, nymphs and adult females using publicly available RNA sequencing (RNA-seq) data to elucidate the overarching transcriptomic differences between these developmental stages. Principal component analysis and hierarchical clustering analysis unveiled distinct separations among samples across different developmental stages, regardless of their Wolbachia infection status. Differential expression analysis revealed 4,089,2,762, and 1,282 core genes specifically enriched in eggs, nymphs, and adults, respectively. KEGG and GO enrichment analyses showed upregulation of genes in eggs are associated with proteolysis, Wnt signaling pathway, DNA transcription, RNA biosynthetic and metabolic processes, as well as protein folding, sorting, and degradation pathways. Meanwhile, nymphs exhibited increased abundance of genes related to chitin/amino sugar metabolic processes, G protein-coupled receptor signaling pathways, monoatomic ion transport, and neurotransmitter transport pathways. Pathways involving sphingolipid and carbohydrate metabolic processes, proteolysis, lipid transport, and localization were particularly enriched in older females. Altogether, our findings suggest that the egg stage exhibits higher activity in cell differentiation processes, the nymph stage is more involved in chitin development, and the adult stage shows increased metabolic and reproductive activity. This study enhances our understanding of the molecular mechanisms underlying TSSM development and paves the way for further research into the intricate physiological processes of TSSM.

Decoding plant-induced transcriptomic variability and consistency in two related polyphagous mites differing in host ranges.

The diet breadth of generalist herbivores when compared to specialists tends to be associated with greater transcriptional plasticity. Here, we consider whether it may also contribute to variation in host range among two generalists with different levels of polyphagy. We examined two related polyphagous spider mites with different host ranges, Tetranychus urticae (1200 plants) and Tetranychus truncatus (90 plants). Data from multiple populations of both species domesticated on common beans and transferred to new plant hosts (cotton, cucumber, eggplant) were used to investigate transcriptional plasticity relative to population-based variation in gene expression. Compared to T. truncatus, T. urticae exhibited much higher transcriptional plasticity. Populations of this species also showed much more variable expression regulation in response to a plant host, particularly for genes related to detoxification, transport, and transcriptional factors. In response to the different plant hosts, both polyphagous species showed enriched processes of drug/xenobiotics metabolism, with T. urticae orchestrating a relatively broader array of biological pathways. Through co-expression network analysis, we identified gene modules associated with host plant response, revealing shared hub genes primarily involved in detoxification metabolism when both mites fed on the same plants. After silencing a shared hub CYP gene related to eggplant exposure, the performance of both species on the original bean host improved, but the fecundity of T. truncatus decreased when feeding on eggplant. The extensive transcriptomic variation shown by T. urticae might serve as a potential compensatory mechanism for a deficiency of hub genes in this species. This research points to nuanced differences in transcriptomic variability between generalist herbivores.

A QTL GN1.1, encoding FT-L1, regulates grain number and yield by modulating polar auxin transport in rice.

Rice grain number is a crucial agronomic trait impacting yield. In this study, we characterized a quantitative trait locus (QTL), GRAIN NUMBER 1.1 (GN1.1), which encodes a Flowering Locus T-like1 (FT-L1) protein and acts as a negative regulator of grain number in rice. The elite allele GN1.1B, derived from the Oryza indica variety, BF3-104, exhibits a 14.6% increase in grain yield compared with the O. japonica variety, Nipponbare, based on plot yield tests. We demonstrated that GN1.1 interacted with and enhanced the stability of ADP-ribosylation factor (Arf)-GTPase-activating protein (Gap), OsZAC. Loss of function of OsZAC results in increased grain number. Based on our data, we propose that GN1.1B facilitates the elevation of auxin content in young rice panicles by affecting polar auxin transport (PAT) through interaction with OsZAC. Our study unveils the pivotal role of the GN1.1 locus in rice panicle development and presents a novel, promising allele for enhancing rice grain yield through genetic improvement.

Clinical and MRI risk factors predicting post-irradiation carotid blowout syndrome in patients with nasopharyngeal cancer.

OBJECTIVE: To explore the clinical and imaging features of nasopharyngeal cancer (NPC) complicated by acute carotid blowout syndrome (CBS), analyze the risk factors for CBS, and improve diagnostic vigilance for early intervention. METHODS: This retrospective review was conducted between January 2003 and May 2023. Altogether, 49 patients with post-irradiation NPC with CBS and 49 patients without CBS as control group were enrolled. The condition of the patients when CBS occurred was reviewed. Patient characteristics of the CBS and control groups were compared, and binary logistic regression analysis was performed to identify risk factors for CBS. RESULTS: All patients in the CBS group were conscious, and 41 patients had a Karnofsky performance assessment scale score of ≥ 70. After interventional therapy, 43 patients survived (the mean survival time of patients after CBS was 3.2 ± 2.1 years). Compared with the control group, the CBS group had a higher incidence of sphenoid sinusitis (81% vs. 52.4%), osteonecrosis (82.9% vs. 51.2%), artery exposure (29.3% vs. 4.9%), and internal carotid artery injury (61% vs. 29.3%). Osteonecrosis and artery exposure were selected as important risk factor for CBS, with p-values of 0.016 and 0.031, respectively. CONCLUSION: CBS is an important factor that affects the survival of patients with NPC. If internal carotid artery injury, artery exposure, sphenoid sinusitis, and osteonecrosis are present, especially the latter two signs, the possibility of CBS should be considered.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury.

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.

An investigation of the prevalence and diversity of Anisakis in China: marine food safety implications.

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.

Empagliflozin alleviates neuroinflammation by inhibiting astrocyte activation in the brain and regulating gut microbiota of high-fat diet mice.

A high-fat diet can modify the composition of gut microbiota, resulting in dysbiosis. Changes in gut microbiota composition can lead to increased permeability of the gut barrier, allowing bacterial products like lipopolysaccharides (LPS) to enter circulation. This process can initiate systemic inflammation and contribute to neuroinflammation. Empagliflozin (EF), an SGLT2 inhibitor-type hypoglycemic drug, has been reported to treat neuroinflammation. However, there is a lack of evidence showing that EF regulates the gut microbiota axis to control neuroinflammation in HFD models. In this study, we explored whether EF could improve neuroinflammation caused by an HFD via regulation of the gut microbiota and the mechanism underlying this phenomenon. Our data revealed that EF alleviates pathological brain injury, reduces the reactive proliferation of astrocytes, and increases the expression of synaptophysin. In addition, the levels of inflammatory factors in hippocampal tissue were significantly decreased after EF intervention. Subsequently, the results of 16S rRNA gene sequencing showed that EF could change the microbial community structure of mice, indicating that the abundance of Lactococcus, Ligilactobacillus and other microbial populations decreased dramatically. Therefore, EF alleviates neuroinflammation by inhibiting gut microbiota-mediated astrocyte activation in the brains of high-fat diet-fed mice. Our study focused on the gut-brain axis, and broader research on neuroinflammation can provide a more holistic understanding of the mechanisms driving neurodegenerative diseases and inform the development of effective strategies to mitigate their impact on brain health. The results provide strong evidence supporting the larger clinical application of EF.

Alzheimer-like behavior and synaptic dysfunction in 3 × Tg-AD mice are reversed with calcineurin inhibition.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Current treatments are unable to achieve satisfactory therapeutic effects or reverse the progression of the disease. Calcineurin has been implicated as part of a critical signaling pathway for learning and memory, and neuronal calcineurin may be hyperactivated in AD. To investigate the effects and underlying mechanisms of FK506, a calcineurin inhibitor, on Alzheimer-like behavior and synaptic dysfunction in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease, we investigated the effect of FK506 on cognitive function and synaptic plasticity in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease. The results showed that FK506 treatment ameliorated cognitive deficits, as indicated by the decreased latency in the water maze, and attenuated tau hyperphosphorylation in 3 × Tg-AD mice. Treatment with FK506 also reduced the levels of certain markers of postsynaptic deficits, including PSD-95 and NR2B, and reversed the long-term potentiation deficiency and dendritic spine impairments in 3 × Tg-AD mice. These findings suggest that treatment with calcineurin inhibitors such as FK506 can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial Alzheimer's disease and related tauopathies.

Correction: Zhao et al. Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN). Cells 2020, 9, 559.

In the original publication [...].

Curcumin Inhibits α-Synuclein Aggregation by Acting on Liquid-Liquid Phase Transition.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.

Clinical characteristics, radiological features and outcomes in pulmonary involvement of cryoglobulinemia.

BACKGROUND: Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood. METHODS: Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia. RESULTS: The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001). CONCLUSIONS: A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome.

Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

Clinical value of the Patient Global Assessment with Ankylosing Spondylitis: A cross-sectional study.

To analyze the factors associated with the overall patient condition and explore the clinical value of the Patient Global Assessment (PGA) index for assessing the disease state in patients with Ankylosing Spondylitis (AS). This cross-sectional study used a standardized questionnaire to record the basic information of patients with AS. The collected data included the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP), ASDAS-erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), PGA, and other clinical indicators. Statistical analysis was performed using SPSS 25.0 software, and the scale was assessed for retest reliability and structural validity. The Kruskal-Wallis H test and Spearman or Pearson correlation analysis were used to analyze the factors influencing PGA scores. The receiver operator characteristic (ROC) curve was used to identify the cutoff value of the PGA for predicting disease activity in AS. The patient age, disease duration, family history, and history of ocular inflammation significantly differed between PGA groups (P < .05). The median PGA was significantly lower in patients with disease remission than in those with disease activity (P < .01). The various clinical indexes significantly differed between PGA groups (P < .01). The PGA was significantly correlated with various clinical indicators (P < .01). The area under the ROC curve (AUC) for disease activity based on the ASDAS-CRP was 0.743 (P < .01) with a PGA cutoff value of 1.38; the AUC for disease activity based on the BASDAI was 0.715 (P < .01) with a PGA cutoff value of 1.63. The PGA was significantly correlated with patient-reported outcomes, disease activity, function, and psychological status, and may indicate the level of inflammation in patients with AS. A PGA of around 1.5 indicates disease activity.

Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy.

BACKGROUND: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. METHODS: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. RESULTS: A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. CONCLUSIONS: Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients.