Psoriasis (PsO) is a chronic, systemic, immune-mediated disease with multiorgan involvement. Psoriatic arthritis (PsA) is an inflammatory arthritis that is present in 6%-42% of patients with PsO. ...Approximately 15% of patients with PsO have undiagnosed PsA. Predicting patients with a risk of PsA is crucial for providing them with early examination and treatment that can prevent irreversible disease progression and function loss.
The aim of this study was to develop and validate a prediction model for PsA based on chronological large-scale and multidimensional electronic medical records using a machine learning algorithm.
This case-control study used Taiwan's National Health Insurance Research Database from January 1, 1999, to December 31, 2013. The original data set was split into training and holdout data sets in an 80:20 ratio. A convolutional neural network was used to develop a prediction model. This model used 2.5-year diagnostic and medical records (inpatient and outpatient) with temporal-sequential information to predict the risk of PsA for a given patient within the next 6 months. The model was developed and cross-validated using the training data and was tested using the holdout data. An occlusion sensitivity analysis was performed to identify the important features of the model.
The prediction model included a total of 443 patients with PsA with earlier diagnosis of PsO and 1772 patients with PsO without PsA for the control group. The 6-month PsA risk prediction model that uses sequential diagnostic and drug prescription information as a temporal phenomic map yielded an area under the receiver operating characteristic curve of 0.70 (95% CI 0.559-0.833), a mean sensitivity of 0.80 (SD 0.11), a mean specificity of 0.60 (SD 0.04), and a mean negative predictive value of 0.93 (SD 0.04).
The findings of this study suggest that the risk prediction model can identify patients with PsO at a high risk of PsA. This model may help health care professionals to prioritize treatment for target high-risk populations and prevent irreversible disease progression and functional loss.
In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 ...to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes
,
,
, and
genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.
We describe herein the preparation of certain 2-substituted 3-arylquinoline derivatives and the evaluation of their anti-inflammatory effects in LPS-activated murine J774A.1 macrophage cells. Among ...these newly synthesized 2-substituted 3-arylquinoline derivatives, 2-(4-methoxy- benzoyl)-3-(3,4,5-trimethoxyphenyl)quinoline (
) and 2-(4-fluorobenzoyl)-3-(3,4,5-trimethoxy- phenyl)quinoline (
) are two of the most active compounds which can inhibit the production of NO at non-cytotoxic concentrations. Our results have also indicated that compounds
and
significantly decrease the secretion of pro-inflammatory cytokines (TNF-á and IL-6), inhibit the expression of iNOS, suppress the phosphorylation of MAPKs, and attenuate the activity of NF-êB by LPS-activated macrophages. Through molecular docking analysis, we found that
could fit into the middle of the TNF-á dimer and form hydrophobic interactions with Leu55, Leu57 chain A and B, Tyr59, Val123 chain B and D, Ile 155. These results suggest that both
and
are potential lead compounds in inhibiting LPS-induced inflammatory responses. Further structural optimization to discover novel anti-inflammatory agents is ongoing.
Purpose
Several studies have explored the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). However, the extent to which NSAIDs may increase or decrease ...the risk of PD remains unresolved. We, therefore, performed a meta-analysis of relevant studies to quantify the magnitude of the association between NSAID use and PD risk in the elderly population.
Methods
The electronic databases such as PubMed, EMBASE, Scopus, Google Scholar, and Web of Science were used to search the relevant articles published between January 1990 and December 2017. Large (
n
≥ 1000) observational design studies with a follow-up at least 1 year were considered. Two authors independently extracted information from the included studies. Random effect model was used to calculate risk ratios (RRs) with 95% confidence interval (Cl).
Results
A total of 17 studies with 2,498,258 participants and nearly 14,713 PD patients were included in the final analysis. The overall pooled RR of PD was 0.95 (95%CI 0.860–1.048) with significant heterogeneity (
I
2
= 63.093,
Q
= 43.352,
p
< 0.0001). In the subgroup analysis, the overall pooled RR of PD was 0.90 (95%CI 0.738–1.109), 0.96 (95%CI 0.882–1.055), and 0.99 (95%CI 0.841–0.982) from the studies of North America, Europe, and Asia. Additionally, long-term use, study design, individual NSAID use, and risk of PD were also evaluated.
Conclusion
Despite the neuroprotective potential of NSAIDs demonstrated in some experimental studies, our findings suggest that there is no association between NSAIDs and the risk of Parkinson disease at the population level. Until further evidence is established, clinicians need to be vigilant ensuring that the use of NSAIDs remains restricted to their approved anti-inflammatory and analgesic effect.
Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and a leading cause of cancer worldwide. Histone deacetylases (HDACs), which regulate cell proliferation and survival, are ...associated with the development and progression of cancer. Moreover, HDAC inhibitors are promising therapeutic targets, with five HDAC inhibitors approved for cancer treatment to date. However, their safety profile necessitates the exploration of well-tolerated HDAC inhibitors that can be used in cancer therapeutic strategies. In this study, the pan-HDAC inhibitor MPT0G236 reduced the viability and inhibited the proliferation of human colorectal cancer cells, and normal human umbilical vein endothelial cells (HUVECs) showed reduced sensitivity. These findings indicated that MPT0G236 specifically targeted malignant tumor cells. Notably, MPT0G236 significantly inhibited the activities of HDAC1, HDAC2, and HDAC3, Class I HDACs, as well as HDAC6, a Class IIb HDAC, at low nanomolar concentrations. Additionally, it promoted the accumulation of acetyl-α-tubulin and acetyl-histone H3 in HCT-116 and HT-29 cells in a concentration-dependent manner. Furthermore, MPT0G236 treatment induced G2/M cell cycle arrest in CRC cells by initially regulating the levels of cell-cycle-related proteins, such as p-MPM2; specifically reducing p-cdc2 (Y15), cyclin B1, and cdc25C levels; and subsequently inducing apoptosis through the caspase-dependent pathways and PARP activation. Our findings demonstrate that MPT0G236 exhibits significant anticancer activity in human colorectal cancer cells.
High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor ...mobility remains unclear. Therefore, we aimed to investigate whether HMGB1 affects mitochondria distribution and regulates dynamin-related protein 1 (DRP1)-mediated lamellipodia/filopodia formation to promote NSCLC migration. The regulation of mitochondrial membrane tension, dynamics, polarization, fission process, and cytoskeletal rearrangements in lung cancer cells by HMGB1 was analyzed using confocal microscopy. The HMGB1-mediated regulation of DRP1 phosphorylation and colocalization was determined using immunostaining and co-immunoprecipitation assays. The tumorigenic potential of HMGB1 was assessed in vivo and further confirmed using NSCLC patient samples. Our results showed that HMGB1 increased the polarity and mobility of cells (mainly by regulating the cytoskeletal system actin and microtubule dynamics and distribution), promoted the formation of lamellipodia/filopodia, and enhanced the expression and phosphorylation of DRP1 in both the nucleus and cytoplasm. In addition, HMGB1 and DRP1 expressions were positively correlated and exhibited poor prognosis and survival in patients with lung cancer. Collectively, HMGB1 plays a key role in the formation of lamellipodia and filopodia by regulating cytoskeleton dynamics and DRP1 expression to promote lung cancer migration.
Aortic wall inflammation, abnormal oxidative stress and progressive degradation of extracellular matrix proteins are the main characteristics of abdominal aortic aneurysms (AAAs). The ...nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome dysregulation plays a crucial role in aortic damage and disease progression. The first aim of this study was to examine the effect of baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) on AAA formation in apolipoprotein E-deficient (ApoE−/−) mice. The second aim was to define whether baicalein attenuates aberrant vascular smooth muscle cell (VSMC) proliferation and inflammation in VSMC culture. For male ApoE−/− mice, a clinically relevant AAA model was randomly divided into four groups: saline infusion, baicalein intraperitoneal injection, Angiotensin II (Ang II) infusion and Ang II + baicalein. Twenty-seven days of treatment with baicalein markedly decreased Ang II-infused AAA incidence and aortic diameter, reduced collagen-fiber formation, preserved elastic structure and density and prevented smooth muscle cell contractile protein degradation. Baicalein inhibited rat VSMC proliferation and migration following the stimulation of VSMC cultures with Ang II while blocking the Ang II-inducible cell cycle progression from G0/G1 to the S phase in the synchronized cells. Cal-520 AM staining showed that baicalein decreased cellular calcium in Ang II-induced VSMCs; furthermore, a Western blot assay indicated that baicalein inhibited the expression of PCNA and significantly lowered levels of phospho-Akt and phospho-ERK, along with an increase in baicalein concentration in Ang II-induced VSMCs. Immunofluorescence staining showed that baicalein pretreatment reduced NF-κB nuclear translocation in Ang II-induced VSMCs and furthered the protein expressions of NLRP3 while ASC and caspase-1 were suppressed in a dose-dependent manner. Baicalein pretreatment upregulated Nrf2/HO-1 signaling in Ang II-induced VSMCs. Thus, 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed that its reactive oxygen species (ROS) production decreased, along with the baicalein pretreatment. Our overall results indicate that baicalein could have therapeutic potential in preventing aneurysm development.
Barriers to smartphone use often exist among older adults, and increasing smartphone use is beneficial to increasing older adults' quality of life. Studies of older adults' smartphone use intentions ...have mostly adopted the technology acceptance model or unified theory of acceptance and use of technology (UTAUT). However, these models have their limitations. A meta-UTAUT has been developed, but it has not been extensively verified with older adults. This study used the meta-UTAUT model to explore the influences on older adults' smartphone use intentions and behaviors. A total of 311 adults aged 60 to 75 years who had minimal experience with smartphones were recruited. They participated in a 16 h smartphone training and then completed a questionnaire. The results demonstrated that the meta-UTAUT model can predict older adults' smartphone use intentions and behaviors. Performance expectancy (PE) and social influence significantly influenced behavioral intention (BI) and attitude toward using smartphones (AT). PE was the strongest factor influencing BI. AT also affected BI. Although facilitating conditions did not significantly affect BI, they had a high influence on AT. To increase smartphone use among older adults, training can be implemented to teach smartphone skills and emphasize the benefits of using smartphones.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, but the underlying pathophysiological mechanisms of ADHD remain unclear. Gut microbiota has been recognized to ...influence brain function and behaviors. Therefore, this study aimed to determine whether imbalanced gut microbiomes identified by a 16S rRNA sequencing approach are involved in the pathophysiology of ADHD. We recruited a total of 30 children with ADHD (mean age: 8.4 years) and a total of 30 healthy controls (mean age: 9.3 years) for this study. The dietary patterns of all participants were assessed with the food frequency questionnaire. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. We found that the gut microbiota communities in ADHD patients showed a significantly higher Shannon index and Chao index than the control subjects. Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between ADHD patients and healthy controls. The relative abundance of
Bacteroides coprocola
(
B. coprocola
) was decreased, while the relative abundance of
Bacteroides uniformis
(
B. uniformis
),
Bacteroides ovatus
(
B. ovatus
), and
Sutterella stercoricanis
(
S. stercoricanis
) were increased in the ADHD group. Of all participants,
S. stercoricanis
demonstrated a significant association with the intake of dairy, nuts/seeds/legumes, ferritin and magnesium.
B. ovatus
and
S. stercoricanis
were positively correlated to ADHD symptoms. In conclusion, we suggest that the gut microbiome community is associated with dietary patterns, and linked to the susceptibility to ADHD.
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