MicroRNA-146a Signature in Psoriasis: A Systematic Review and Meta-Analysis.

BACKGROUND: Psoriasis is a chronic, inflammatory, T-cell-mediated disease with a multifactorial pathogenesis. MicroRNA (miRNA) alteration in psoriasis has been identified within the last few years. In particular, miR-146a levels were altered. However, previous studies have equivocal or even contradictory findings. OBJECTIVE: The current study aimed to perform a systematic review and meta-analysis to evaluate the miRNA expression profile in different tissues in patients with psoriasis. Further, the correlation between miR-146a levels and psoriasis severity as well as the specific expression patterns of the miR-146a profile in patients with psoriasis after treatment were evaluated. METHODS: To retrieve studies investigating the correlation between miRNA and psoriasis, a comprehensive search of databases including PubMed, Cochrane Library, and Embase was performed from inception to 30 June 2023. Relevant journals and references of the included studies were also reviewed. A meta-analysis was conducted using the comprehensive meta-analysis version 3. RESULTS: The correlation between the miR-146a expression levels and psoriasis susceptibility in 14 studies was assessed. Results showed that the miR-146a expression level was upregulated in psoriasis samples [P = 0.001, standardized mean difference (SMD) = 1.489, 95% confidence interval (CI) = 0.618-2.360]. In a subgroup analysis based on sample type, the correlation between the peripheral blood mononuclear cell, blood, and tissue miR-146a expression level and psoriasis was significant (SMD = 1.293, 95% CI 0.310-2.276, P = 0.01; SMD = 2.526, 95% CI 1.710-3.342, P = 0.000; SMD = 3.153, 95% CI 1.432-4.874, P = 0.00, respectively). A positive correlation was observed between the miR-146a expression levels and Psoriasis Area and Severity Index (PASI) score. However, the result was not statistically significant (correlation coefficient = 0.29, 95% CI - 0.038 to 0.575, P = 0.081). Further, the miR-146a levels decreased after treatment (SMD = - 1.592, 95% CI - 2.067 to - 1.117, P = 0.000, I2 = 74.104). CONCLUSIONS: The miR-146a expression level is positively correlated with and can contribute to the pathobiology of psoriasis.

Anti-Inflammatory Effects of Anthocyanin-Enriched Black Soybean Seed Coat (BSSC) Crude Extract on LPS-Induced Acute Liver Injury in Mice.

Soybeans rank among the top five globally produced crops. Black soybeans contain anthocyanins in their seed coat, offering strong antioxidant and anti-inflammatory benefits. This study explores the protective effects of black soybean seed coat (BSSC) against acute liver injury (ALI) in mice. Mice pretreated with BSSC crude extract showed reduced liver damage, inflammation, and apoptosis. High doses (300 mg/kg) of the extract decreased levels of proinflammatory cytokines (IL-6, IFN-γ) and increased levels of anti-inflammatory ones (IL-4, IL-10), alongside mitigating liver pathological damage. Additionally, it influenced the Nrf2/HO-1 pathway and reduced levels of apoptosis-related proteins. In vitro, the compounds delphinidin-3-O-glucoside (D3G) and cyanidin-3-O-glucoside (C3G) in BSSC were found to modulate cytokine levels, suggesting their role in ALI protection. The study concludes that BSSC extract, particularly due to D3G and C3G, effectively protects against LPS-induced ALI in mice by inhibiting inflammation, oxidative stress, and apoptosis.

Oral Dexmedetomidine Achieves Superior Effects in Mitigating Emergence Agitation and Demonstrates Comparable Sedative Effects to Oral Midazolam for Pediatric Premedication: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

Background: Oral midazolam is the most commonly used sedative premedication agent in pediatric patients. While effective, oral midazolam cannot reduce the incidence of emergence agitation. Oral dexmedetomidine may be effective in providing satisfactory sedation and reduce the incidence of emergence agitation, although the results of different randomized controlled trials are conflicting. Methods: This study enrolled randomized controlled trials (RCTs) examining premedication with oral dexmedetomidine versus oral midazolam in pediatric patients undergoing general anesthesia. PubMed, the Cochrane Library, Embase, and the Web of Science database were searched from their inception until June 2023. The outcomes were the incidence of satisfactory preoperative sedation, satisfactory sedation during separation from parents, satisfactory sedation during anesthesia induction using an anesthesia mask, and the incidence of emergence agitation. Results: A total of 9 RCTs comprising 885 patients were analyzed. Our data revealed comparable effects of dexmedetomidine and midazolam with respect to satisfactory preoperative sedation and a satisfactory incidence of sedation during parental separation and mask acceptance before anesthesia induction. Notably, our data revealed that the rate of emergence agitation was significantly lower in pediatric patients receiving dexmedetomidine (n = 162) than in those receiving midazolam (n = 159) (odds ratio = 0.16; 95% confidence interval: 0.06 to 0.44; p < 0.001; I2 = 35%). Conclusions: Data from this meta-analysis revealed comparable effects for premedication with oral dexmedetomidine or oral midazolam with respect to satisfactory sedation; furthermore, premedication with oral dexmedetomidine more effectively mitigated emergence agitation in pediatric patients receiving general anesthesia compared with oral midazolam.

Synthesis and Characterization of DOPO-Containing Poly(2,6-dimethyl-1,4-phenylene oxide)s by Oxidative Coupling Polymerization.

A set of polyphenylene oxides incorporating DOPO (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide) functionality, denoted as DOPO-R-PPO, was synthesized by copolymerization of 2,6-dimethylphenol (2,6-DMP) with various DOPO-substituted tetramethyl bisphenol monomers. In the initial step, a Friedel-Crafts acylation reaction was employed to react 2,6-DMP with different acyl chlorides, leading to the formation of ketone derivatives substituted with 2,6-dimethylphenyl groups. Subsequently, the ketones, along with DOPO and 2,6-DMP, underwent a condensation reaction to yield a series of DOPO-substituted bisphenol derivatives. Finally, polymerizations of 2,6-dimethylphenol with these DOPO-substituted bisphenols were carried out in organic solvents using copper(I) bromide/N-butyldimethylamine catalysts (CuBr/DMBA) under a continuous flow of oxygen, yielding telechelic PPO oligomers with DOPO moieties incorporated into the polymer backbone. The chemical structures of the synthesized compounds were characterized using various analytical techniques, including Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), phosphorus nuclear magnetic resonance (31P NMR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). When compared to conventional poly(2,6-dimethyl-1,4-phenylene oxide)s with a similar molecular weight range, all DOPO-PPOs exhibited higher glass transition temperatures, enhanced thermal degradability, and increased char yield formation at 800 °C without compromising solubility in organic solvents.

MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2-GPX2 Molecular Axis in Head-Neck Cancer.

Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads to local recurrence, becoming a substantial factor in treatment failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs to inhibit protein translation. Although several studies have indicated that the dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family's role in radioresistance remains limited. This study determined the role of miR-630 in regulating radiosensitivity in HNC. We discovered that miR-630 functions as an oncomiR, marked by its overexpression in HNC patients, correlating with a poorer prognosis. We further delineated the malignant function of miR-630 in HNC cells. While it had a minimal impact on cell growth, the miR-630 contributed to radioresistance in HNC cells. This result was supported by decreased cellular apoptosis and caspase enzyme activities. Moreover, miR-630 overexpression mitigated irradiation-induced DNA damage, evidenced by the reduced levels of the γ-H2AX histone protein, a marker for double-strand DNA breaks. Mechanistically, the overexpression of miR-630 decreased the cellular ROS levels and initiated Nrf2 transcriptional activity, resulting in the upregulation of the antioxidant enzyme GPX2. Thus, this study elucidates that miR-630 augments radioresistance by inducing an anti-apoptotic effect via the Nrf2-GPX2 molecular axis in HNC. The modulation of miR-630 may serve as a novel radiosensitizing target for HNC.

Risk factors for poor progression of addictive internet use across different COVID-19 periods in China.

BACKGROUND AND OBJECTIVES: Addictive behaviors are serious factors for mental health and usually increase during public crises. We identified the vulnerable characteristics for bad prognosis of addictive internet use across different periods of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Self-reported questionnaires were delivered in three waves through jdh.com during the outbreak (n = 17,960), remission (n = 15,666), and dynamic zero (n = 12,158) periods of COVID-19 pandemic in China. Internet addiction degree was assessed using the Internet Addiction Test. The different progression groups were divided using a latent class growth model among 1679 longitudinal participants. Risk factors for bad progression were identified by two-step logistic regression. RESULTS: A total of 40.16% of participants reported an increase in the addictive degree of internet use compared with prepandemic. Across different COVID-19 periods, the overall trend of addictive internet use was downward among general Chinese study participants (Mslope = -1.56). Childhood traumatic experiences, deterioration of physical health, depression, and anxiety during remission and dynamic periods were the main risk factors for the bad progression of pandemic-induced addictive internet use. DISCUSSION AND CONCLUSIONS: Addictive internet use was remitted following relaxed control policies during the COVID-19 pandemic. Negative childhood experiences and bad mental status during the recovery period were harmful to coping with pandemic-related addictive internet use. SCIENTIFIC SIGNIFICANCE: Our findings profiled the general trend of addictive internet use and the vulnerable characteristics of its bad progression across different periods of the first wave of COVID-19 pandemic in China. Our findings provide valuable insights for preventing the long-term adverse effects of negative public events on Internet addiction.

Risk Stratification for Herpes Simplex Virus Pneumonia Using Elastic Net Penalized Cox Proportional Hazard Algorithm with Enhanced Explainability.

Herpes simplex virus (HSV) pneumonia is a serious and often fatal respiratory tract infection that occurs in immunocompromised individuals. The early detection of accurate risk stratification is essential in identifying patients who are at high risk of mortality and may benefit from more aggressive treatment. In this study, we developed and validated a risk stratification model for HSV bronchopneumonia using an elastic net penalized Cox proportional hazard algorithm. We analyzed data from a cohort of 104 critically ill patients with HSV bronchopneumonia identified in Chang Gung Memorial Hospital, Linkou, Taiwan: one of the largest tertiary medical centers in the world. A total of 109 predictors, both clinical and laboratory, were identified in this process to develop a risk stratification model that could accurately predict mortality in patients with HSV bronchopneumonia. This model was able to differentiate the risk of death and predict mortality in patients with HSV bronchopneumonia compared to the APACHE II score in the early stage of ICU admissions. Both hazard ratio coefficient and selection frequency were used as the metrics to enhance the explainability of the informative predictors. Our findings suggest that the elastic net penalized Cox proportional hazard algorithm is a promising tool for risk stratification in patients with HSV bronchopneumonia and could be useful in identifying those at high risk of mortality.

Achieving a Highly Stable Perovskite Photodetector with a Long Lifetime Fabricated via an All-Vacuum Deposition Process.

Hybrid organic-inorganic metal halide perovskites (HOIP) have become a promising visible light sensing material due to their excellent optoelectronic characteristics. Despite the superiority, overcoming the stability issue for commercialization remains a challenge. Herein, an extremely stable photodetector was demonstrated and fabricated with Cs0.06FA0.94Pb(I0.68Br0.32)3 perovskite by an all-vacuum process. The photodetector achieves a current density up to 1.793 × 10-2 A cm-2 under standard one sun solar illumination while maintaining a current density as low as 8.627 × 10-10 A cm-2 at zero bias voltage. The linear dynamic range (LDR) and transient voltage response were found to be comparable to the silicon-based photodetector (Newport 818-SL). Most importantly, the device maintains 95% of the initial performance after 960 h of incessant exposure under one sun solar illumination. The achievements of these outstanding results contributed to the all-vacuum deposition process delivering a film with high stability and good uniformity, which in turn delays the degradation process. The degradation mechanism is further investigated by impedance spectroscopy to reveal the charge dynamics in the photodetector under different exposure times.

Treating fibromyalgia with electrical neuromodulation: A systematic review and meta-analysis.

OBJECTIVE: Several types of electrical neuromodulation (such as transcranial direct current stimulation, tDCS; transcutaneous electrical nerve stimulation) have been applied in the treatment of fibromyalgia. These trials had different outcome measurements, such as subjective pain, pain threshold, depression, anxiety, and functioning. We intended to integrate data from different trials into a meta-analysis to clearly present the clinical value of electrical neuromodulation in fibromyalgia. METHODS: A systematic review and meta-analysis of randomized controlled trials comparing the effect of all types of electrical neuromodulation in patients with fibromyalgia was conducted. The main outcome was subjective pain; the secondary outcomes included depression, anxiety, and functioning. RESULTS: Twenty-five studies and 1061 fibromyalgia patients were included in the quantitative analysis. Active electrical neuromodulation and active tDCS both showed significant effects on subjective pain, depression, and functioning. For different anode tDCS electrode positions, only F3-F4 revealed a significant effect on depression. Meta-regression tDCS effects on depression were significantly associated with age. CONCLUSIONS: Electrical neuromodulation is significantly effective in treating pain, depression, and functioning in patients with fibromyalgia. SIGNIFICANCE: The results may help clinicians to arrange effective treatment plans for patients with fibromyalgia, especially in those patients who reveal limited response to pharmacotherapy and psychotherapy.

Risk Factors for Influenza-Induced Exacerbations and Mortality in Non-Cystic Fibrosis Bronchiectasis.

Influenza infection is a cause of exacerbations in patients with chronic pulmonary diseases. The aim of this study was to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. Using the Chang Gung Research Database, we identified patients with bronchiectasis and influenza-related infection (ICD-9-CM 487 and anti-viral medicine) between 2008 and 2017. The main outcomes were influenza-related hospitalization and in-hospital mortality rate. Eight hundred sixty-five patients with bronchiectasis and influenza infection were identified. Five hundred thirty-six (62%) patients with bronchiectasis were hospitalized for influenza-related infection and 118 (22%) patients had respiratory failure. Compared to the group only seen in clinic, the hospitalization group was older, with more male patients, a lower FEV1, higher bronchiectasis aetiology comorbidity index (BACI), and more acute exacerbations in the previous year. Co-infections were evident in 55.6% of hospitalized patients, mainly caused by Pseudomonas aeruginosa (15%), fungus (7%), and Klebsiella pneumoniae (6%). The respiratory failure group developed acute kidney injury (36% vs. 16%; p < 0.001), and shock (47% vs. 6%; p < 0.001) more often than influenza patients without respiratory failure. The overall mortality rate was 10.8% and the respiratory failure group exhibited significantly higher in-hospital mortality rates (27.1% vs. 6.2%; p < 0.001). Age, BACI, and previous exacerbations were independently associated with influenza-related hospitalization. Age, presence of shock, and low platelet counts were associated with increased hospital mortality. Influenza virus caused severe exacerbation in bronchiectasis, especially in those who were older and who had high BACI scores and previous exacerbations. A high risk of respiratory failure and mortality were observed in influenza-related hospitalization in bronchiectasis. We highlight the importance of preventing or treating influenza infection in bronchiectasis.

Development of Furanopyrimidine-Based Orally Active Third-Generation EGFR Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is described. First, selectivity for mutant EGFR was accomplished by replacing the (S)-2-phenylglycinol moiety of 12 with either an ethanol or an alkyl substituent. Then, the cellular potency and physicochemical properties were optimized through insights from molecular modeling studies by implanting various solubilizing groups in phenyl rings A and B. Optimized lead 52 shows 8-fold selective inhibition of H1975 (EGFRL858R/T790M overexpressing) cancer cells over A431 (EGFRWT overexpressing) cancer cells; western blot analysis further confirmed EGFR mutant-selective target modulation inside the cancer cells by 52. Notably, 52 displayed in vivo antitumor effects in two different mouse xenograft models (BaF3 transfected with mutant EGFR and H1975 tumors) with TGI = 74.9 and 97.5% after oral administration (F = 27%), respectively. With an extraordinary kinome selectivity (S(10) score of 0.017), 52 undergoes detailed preclinical development.

A Biomimetic Bilayer Hydrogel Actuator Based on Thermoresponsive Gelatin Methacryloyl-Poly(N-isopropylacrylamide) Hydrogel with Three-Dimensional Printability.

Development of hydrogel-based actuators with programmable deformation is an important topic that arouses much attention in fundamental and applied research. Most of these actuators are nonbiodegradable or work under nonphysiological conditions. Herein, a temperature-responsive and biodegradable gelatin methacryloyl (GelMA)-poly(N-isopropylacrylamide) hydrogel (i.e., GN hydrogel) network was explored as the active layer of a bilayer actuator. Small-angle X-ray scattering (SAXS) revealed that the GN hydrogel formed a mesoglobular structure (∼230 Å) upon a thermally induced phase transition. Rheological data supported that the GN hydrogel possessed 3D printability and tunable mechanical properties. A bilayer hydrogel actuator composed of active GN and passive GelMA layers was optimized by varying the layer thickness and compositions to achieve large, reproducible, and anisotropic bending with a curvature of ∼5.5 cm-1. Different patterns of the active layer were designed for actuation in programmable control. The 3D printed GN hydrogel constructs showed significant volume reduction (∼25-60% depending on construct design) at 37 °C with the resolution enhanced by the thermo-triggered actuation, while they were able to fully reswell at room temperature. A more intricate 3D printed butterfly actuator demonstrated the ability to mimic the wing movement through thermoresponsiveness. Furthermore, myoblasts laden in the GN hydrogel exhibited significant proliferation of ∼376% in 14 days. This study provides a new fabrication approach for developing biomimetic devices, artificial muscles, and soft robotics for biomedical applications.

Effects of probiotics supplementation on skin photoaging and skin barrier function: A systematic review and meta-analysis.

BACKGROUND: Ultraviolet (UV) irradiation is one of the major causes of skin aging. To date, there remains limited evidence on using oral probiotics for skin anti-photoaging. OBJECTIVES: This systematic review and meta-analysis aims to assess the effects of probiotics on skin photoaging. METHODS: We searched the PubMed and Embase databases for studies published until August 31, 2021, and included randomized controlled trials, murine randomized controlled experiments, and in vitro studies. Skin barrier function was compared between UV irradiated probiotics and controls. RESULTS: After given oral probiotics supplements, a significant reduction was shown in all types of measured MMPs in both murine and in vitro studies. Oral probiotics supplementation significantly reversed UV-induced increase of epidermal thickness (standardized mean differences [SMD] = -1.76; 95% confidence interval [CI] = -3.04 to -0.49; p = .007; I2  = 81%), UV-induced increase trans-epidermal water loss (SMD = -1.72; 95% CI = -2.76 to -0.67; p = .001; I2  = 57%), and UV-induced skin dehydration (SMD = 1.85; 95% CI = 1.16 to 2.55; p < .00001; I2  = 4%). CONCLUSIONS: Probiotics are effective against skin photoaging in terms of MMP pathways and reversing skin barrier function from murine randomized data. Further randomized controlled trials on humans are required to warrant these results.

Can Heart Rate Variability be Viewed as a Biomarker of Problematic Internet Use? A Systematic Review and Meta-Analysis.

Heart rate variability (HRV) has been used to explore the parasympathetic activity of individuals with problematic Internet use (PIU), but the results are controversial. We conducted a systematic review and meta-analysis of studies comparing HRV in PIU individuals and healthy participants from several databases. HRV was analyzed according to the parasympathetic activity in hierarchical order (primary analysis), and the total variability (secondary analysis). The baseline HRV and HRV reactivity were both considered. Of the 106 studies screened, 12 were included in the quantitative analysis. Significant differences were observed for baseline HRV in PIU individuals compared to the controls. Regarding HRV reactivity, PIU individuals did not have a significantly lower HRV value during pleasant or unpleasant stimuli. In summary, PIU individuals and healthy subjects had significantly different resting state parasympathetic activity. The finding of HRV reactivity in PIU individuals awaits further investigation.

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis.

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.

Effect of Whey Protein Supplementation in Postmenopausal Women: A Systematic Review and Meta-Analysis.

(1) Background: Whey protein (WP) in combination with resistance training (RT) is beneficial in improving sarcopenic obesity and its damaging effects in older adults, while the difference between men and women should be considered while interpreting results. This review aims to investigate WP's efficacy on postmenopausal women with or without RT; (2) Material and Methods: We searched electronic databases including PubMed, EMBASE, and the Cochrane Library from inception to August 2021 for randomized controlled trials that included comparison groups to evaluate WP's efficacy in women aged 55 years and above. The outcomes included body composition, muscular strength, functional capacity, and dietary intake. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to estimate the effect of WP. We also performed subgroup analysis with or without RT; (3) Results: We included 14 studies in the systematic review and 10 studies in the meta-analysis. Subgroup analyses showed RT was a major confounder for muscle strength, lean mass, and dietary protein intake (PI). In the RT subgroup, WP supplementation had a significant positive effect on biceps curl strength (BC) (SMD: 0.6805, 95% CI: 0.176, 1.185, I2: 0%), and lower limb lean-mass (LLLM) (SMD: 1.103, 95% CI: 0.632, 1.574, I2: 14%). In the subgroup without RT, a significant negative effect on PI (SMD: -0.4225, 95% CI: -0.774, -0.071, I2: 47%) was observed, while no significant effect on muscle strength or lean mass was revealed. WP supplementation did not show a significantly different effect on fat mass or body weight loss in both the subgroups; (4) Conclusions: In postmenopausal women, WP supplementation only in combination with RT enhances BC and LLLM compared to placebo controls. Without RT, WP has no significant benefit on muscle strength or lean mass.