No genetic causal association between Alzheimer’s disease and osteoporosis: A bidirectional two-sample Mendelian randomization study

ObjectiveMany observational studies have found an association between Alzheimer’s disease (AD) and osteoporosis. However, it is unclear whether there is causal genetic between osteoporosis and AD.MethodsA two-sample Mendelian randomization (MR) study was used to investigate whether there is a causal relationship between osteoporosis and AD. Genes for osteoporosis and AD were obtained from published the genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) with significant genome-wide differences (p < 5 × 10−8) and independent (r2 < 0.001) were selected, and SNPs with F ≥ 10 were further analyzed. Inverse variance weighted (IVW) was used to assess causality, and the results were reported as odds ratios (ORs). Subsequently, heterogeneity was tested using Cochran’s Q test, pleiotropy was tested using the MR–Egger intercept, and leave-one-out sensitivity analysis was performed to assess the robustness of the results.ResultsUsing the IVW method, MR Egger method, and median-weighted method, we found that the results showed no significant causal effect of osteoporosis at different sites and at different ages on AD, regardless of the removal of potentially pleiotropic SNPs. The results were similar for the opposite direction of causality. These results were confirmed to be reliable and stable by sensitivity analysis.ConclusionThis study found that there is no bidirectional causal relationship between osteoporosis and AD. However, they share similar pathogenesis and pathways

Investigating the causal relationship between ankylosing spondylitis and osteoporosis in the European population: a bidirectional Mendelian randomization study

BackgroundAnkylosing Spondylitis (AS) is an inflammatory condition affecting the spine, which may lead to complications such as osteoporosis (OP). Many observational studies have demonstrated a close relationship with strong evidence between OP and AS. The combination of AS and OP is already an indisputable fact, but the exact mechanism of AS complicated with OP is unclear. To better prevent and treat OP in patients with AS, it is necessary to understand the specific mechanism of OP in these patients. In addition, there is a study showing that OP is a risk factor for AS, but the causal relationship between them is not yet clear. Therefore, we conducted a bidirectional Mendelian randomization (MR) analysis to determine whether there is a direct causal effect between AS and OP and to investigate the co-inherited genetic information between the two.MethodsBone mineral density (BMD) was used as a phenotype for OP. The AS dataset was taken from the IGAS consortium and included people of European ancestry (9,069 cases and 13,578 controls). BMD datasets were obtained from the GEFOS consortium, a large GWAS meta-analysis study, and the UK Biobank and were categorized based on site (total body (TB): 56,284 cases; lumbar spine (LS): 28,498 cases; femoral neck (FN): 32,735 cases; forearm (FA): 8,143 cases; and heel: 265,627 cases) and age (0-15: 11,807 cases; 15-30: 4,180 cases; 30-45: 10,062 cases; 45-60: 18,062 cases; and over 60: 22,504 cases).To obtain the casual estimates, the inverse variant weighted (IVW) method was mainly used due to its good statistical power and robustness. The presence of heterogeneity was evaluated using Cochran’s Q test. Pleiotropy was assessed utilizing MR-Egger regression and MR-pleiotropy residual sum and outlier (MR-PRESSO).ResultsGenerally, there were no significant causal associations between genetically predicted AS and decreased BMD levels. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. However, there was a sign of a connection between genetically elevated BMD levels and a decreased risk of AS (Heel-BMD: OR = 0.879, 95% CI: 0.795-0.971, P = 0.012; Total-BMD: OR = 0.948, 95% CI: 0.907-0.990, P = 0.017; LS-BMD: OR = 0.919, 95% CI: 0.861-0.980, P = 0.010). The results were confirmed to be reliable by sensitivity analysis.ConclusionThis MR study found that the causal association between genetic liability to AS and the risk of OP or lower BMD in the European population was not evident, which highlights the second effect (e.g., mechanical reasons such as limited movement) of AS on OP. However, genetically predicted decreased BMD/OP is a risk factor for AS with a causal relationship, implying that patients with OP should be aware of the potential risk of developing AS. Moreover, OP and AS share similar pathogenesis and pathways

Association of immune cell traits with Parkinson’s disease: a Mendelian randomization study

BackgroundImmunity and neuroinflammation play crucial roles in the pathogenesis of Parkinson’s disease (PD). Nonetheless, prior investigations into the correlation between immune inflammation and PD have produced varying results. Identifying specific immune cell phenotypes that are truly associated with PD is challenging, and the causal relationship between immune cells and PD remains elusive.MethodsThis study conducted a comprehensive two-sample Mendelian randomization (MR) analysis, employing five distinct analytical approaches, to clarify the causal connection between immune cell characteristics and the risk of PD. Utilizing GWAS data, we investigated the causal relationship between 731 immune cell traits and PD. These immune cell phenotypes encompass absolute cell (AC) counts, median fluorescence intensity (MFI), and relative cell (RC) counts for B cells, cDCs, mature stage T cells, monocytes, myeloid cells, TBNK (T cells, B cells, and natural killer cells), and Tregs, as well as the logistic parameter (MP) for cDCs and TBNK.ResultsThe inverse variance weighted (IVW) analysis indicated that Myeloid DCs (p = 0.004), HVEM expression on CD45RA− CD4+ T cells (p = 0.007), CD62L− CD86+ Myeloid DCs (p = 0.015), and HLA DR expression on monocytes (p = 0.019) were associated with a reduced risk of PD. CD14+ CD16+ monocytes (p = 0.005), HLA DR+ NK cells within CD3− lymphocytes (p = 0.023), and CD28 expression on activated & secreting Tregs (p = 0.032) were associated with an increased risk of PD.ConclusionThis study establishes a causal link between immune cell phenotype and the pathogenesis of PD, identifying several specific immune cell characteristics associated with PD. This could inspire researchers to delve into the pathogenesis of PD at the cellular subtype level, and aid in the identification of potential pharmacological protein targets for PD

LncRNA-mediated cartilage homeostasis in osteoarthritis: a narrative review

Osteoarthritis (OA) is a degenerative disease of cartilage that affects the quality of life and has increased in morbidity and mortality in recent years. Cartilage homeostasis and dysregulation are thought to be important mechanisms involved in the development of OA. Many studies suggest that lncRNAs are involved in cartilage homeostasis in OA and that lncRNAs can be used to diagnose or treat OA. Among the existing therapeutic regimens, lncRNAs are involved in drug-and nondrug-mediated therapeutic mechanisms and are expected to improve the mechanism of adverse effects or drug resistance. Moreover, targeted lncRNA therapy may also prevent or treat OA. The purpose of this review is to summarize the links between lncRNAs and cartilage homeostasis in OA. In addition, we review the potential applications of lncRNAs at multiple levels of adjuvant and targeted therapies. This review highlights that targeting lncRNAs may be a novel therapeutic strategy for improving and modulating cartilage homeostasis in OA patients

Brain entropy changes in classical trigeminal neuralgia

BackgroundClassical trigeminal neuralgia (CTN) is a common and severe chronic neuropathic facial pain disorder. The pathological mechanisms of CTN are not fully understood. Recent studies have shown that resting-state functional magnetic resonance imaging (rs-fMRI) could provide insights into the functional changes of CTN patients and the complexity of neural processes. However, the precise spatial pattern of complexity changes in CTN patients is still unclear. This study is designed to explore the spatial distribution of complexity alterations in CTN patients using brain entropy (BEN).MethodsA total of 85 CTN patients and 79 age- and sex-matched healthy controls (HCs) were enrolled in this study. All participants underwent rs-fMRI and neuropsychological evaluations. BEN changes were analyzed to observe the spatial distribution of CTN patient complexity, as well as the relationship between these changes and clinical variables. Sixteen different machine learning methods were employed to classify the CTN patients from the HCs, and the best-performing method was selected.ResultsCompared with HCs, CTN patients exhibited increased BEN in the thalamus and brainstem, and decreased BEN in the inferior semilunar lobule. Further analyses revealed a low positive correlation between the average BEN values of the thalamus and neuropsychological assessments. Among the 16 machine learning methods, the Conditional Mutual Information Maximization-Random Forest (CMIM-RF) method yielded the highest area under the curve (AUC) of 0.801.ConclusionsOur study demonstrated that BEN changes in the thalamus and pons and inferior semilunar lobule were associated with CTN and machine learning methods could effectively classify CTN patients and HCs based on BEN changes. Our findings may provide new insights into the neuropathological mechanisms of CTN and have implications for the diagnosis and treatment of CTN

Conflicts Analysis for Inter-Enterprise Business Process Model

Business process (BP) management systems facilitate the understanding and execution of business processes, which tend to change frequently due to both internal and external change in an enterprise. Therefore, the needs for analysis methods to verify the correctness of business process model is becoming more prominent. One key element of such business process is its control flow. We show how a flow specification may contain certain structural conflicts that could compromise its correct execution. In general, identification of such conflicts is a computationally complex problem and requires development of effective algorithms specific for target system language. We present a verification approach and algorithm that employs condition reachable matrix to identify structural conflicts in inter-enterprise business process models. The main contribution of the paper is a new technology for identifying structural conflicts and satisfying well-defined correctness criteria in inter-enterprise business process models

Exogenous melatonin confers drought stress by promoting plant growth, photosynthetic capacity and antioxidant defense system of maize seedlings

Melatonin is an important biologically active hormone that plays a vital role in plant growth and development. In particular, it has been investigated for its roles in abiotic stress management. The current experiment was carried out to investigate the protective role of melatonin in photosynthetic traits and the antioxidant defense system of maize seedling under drought stress. Maize seedlings were subjected to drought stress (40–45% FC) after two weeks of seedling emergence, followed by a foliar spray (0, 25, 50, 75 and 100 µM) and soil drench of melatonin (0, 25, 50, 75 and 100 µM). Our results indicated that drought stress negatively affected maize seedling and decreased plant growth and development, biomass accumulation, reduced chlorophyll, and carotenoid content, and significantly declined photosynthetic rate and stomatal conductance. On the other hand, reactive oxygen species, soluble protein, and proline content increased under drought stress. However, the application of exogenous melatonin reduced the reactive oxygen species burst and enhanced the photosynthetic activity by protecting from damages through activation of various antioxidant enzymes under drought stress. Foliar application of 100 µM and soil drench of 50 µM melatonin was the most effective treatment concentrations under drought stress. Our current findings hereby confirmed the mitigating potential of melatonin application for drought stress by maintaining plant growth, improving the photosynthetic characteristics and activities of antioxidants enzymes