The E2 subunit vaccine has been considered a promising alternative to an attenuated classical swine fever (CSF) vaccine. However, it fails to induce a good cellular immune response. Given that immunogenic adjuvants can regulate the cellular immunity to achieve a maximum efficacy against antigens, immunostimulatory effects of porcine IL-28B on the CSF virus (CSFV) E2 subunit vaccine were evaluated in the present study. We expressed recombinant proteins E2-IL28B, E2, and IL-28B using CHO-S mammalian cells as an antigen expression platform, and three types of CSFV E2 subunit vaccines based on antigens E2-IL28B, E2 + IL-28B, and E2 were prepared, respectively. We found that both E2-IL28B and E2 + IL-28B antigens exhibited superior immunogenicity with dramatically induced antibody titers and neutralizing antibody levels than the E2 alone. Moreover, E2-IL28B or E2 + IL-28B, instead of E2, boosted cellular immune responses via obviously increasing the percentages of CD3+CD4+ T lymphocytes, promoting the lymphocyte proliferations, and enhancing the release of Th1-type cytokines. All results revealed that the inclusion of IL-28B, whether fused or mixed with E2, significantly elevated E2-induced immune potencies, suggesting that IL-28B could be used as a molecular adjuvant to optimize the design of E2 subunit vaccine for more effective controls of the CSF disease. • New CSF E2 subunit vaccine candidates were developed in which IL-28B was an immunoadjuvant • IL-28B significantly elevated the E2-induced immune potency whether it was fused or mixed with E2 • This study provided novel insights into the immunoregulatory properties of IL-28B used for the optimized subunit vaccine design

BackgroundDiabetic nephropathy (DN) is a complication of systemic microvascular disease in diabetes mellitus. Abnormal glycolysis has emerged as a potential factor for chronic renal dysfunction in DN. The current lack of reliable predictive biomarkers hinders early diagnosis and personalized therapy.MethodsTranscriptomic profiles of DN samples and controls were extracted from GEO databases. Differentially expressed genes (DEGs) and their functional enrichments were identified. Glycolysis-related genes (GRGs) were selected by combining DEGs, weighted gene co-expression network, and glycolysis candidate genes. We established a diagnostic signature termed GScore via integrative machine learning framework. The diagnostic efficacy was evaluated by decision curve and calibration curve. Single-cell RNA sequence data was used to identify cell subtypes and interactive signals. The cMAP database was used to find potential therapeutic agents targeting GScore for DN. The expression levels of diagnostic signatures were verified in vitro.ResultsThrough the 108 combinations of machine learning algorithms, we selected 12 diagnostic signatures, including CD163, CYBB, ELF3, FCN1, PROM1, GPR65, LCN2, LTF, S100A4, SOX4, TGFB1 and TNFAIP8. Based on them, an integrative model named GScore was established for predicting DN onset and stratifying clinical risk. We observed distinct biological characteristics and immunological microenvironment states between the high-risk and low-risk groups. GScore was significantly associated with neutrophils and non-classical monocytes. Potential agents including esmolol, estradiol, ganciclovir, and felbamate, targeting the 12 diagnostic signatures were identified. In vitro, ELF3, LCN2 and CD163 were induced in high glucose-induced HK-2 cell lines.ConclusionAn integrative machine learning frame established a novel diagnostic signature using glycolysis-related genes. This study provides a new direction for the early diagnosis and treatment of DN.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and the main cause of end-stage renal disease around the world. Mitochondria are the main organelles responsible for producing energy in cells and are closely involved in maintaining normal organ function. Studies have found that a high-sugar environment can damage glomeruli and tubules and trigger mitochondrial dysfunction. Meanwhile, animal experiments have shown that DKD symptoms are alleviated when mitochondrial damage is targeted, suggesting that mitochondrial dysfunction is inextricably linked to the development of DKD. This article describes the mechanisms of mitochondrial dysfunction and the progression and onset of DKD. The relationship between DKD and mitochondrial dysfunction is discussed. At the same time, the progress of DKD treatment targeting mitochondrial dysfunction is summarized. We hope to provide new insights into the progress and treatment of DKD.

Exosomes, as pivotal entities within the tumor microenvironment, orchestrate intercellular communication through the transfer of diverse molecules, among which non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs play a crucial role. These ncRNAs, endowed with regulatory functions, are selectively incorporated into exosomes. Emerging evidence underscores the significance of exosomal ncRNAs in modulating key oncogenic processes in thyroid cancer (TC), including proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunoediting. The unique composition of exosomes shields their cargo from enzymatic and chemical degradation, ensuring their integrity and facilitating their specific expression in plasma. This positions exosomal ncRNAs as promising candidates for novel diagnostic and prognostic biomarkers in TC. Moreover, the potential of exosomes in the therapeutic landscape of TC is increasingly recognized. This review aims to elucidate the intricate relationship between exosomal ncRNAs and TC, fostering a deeper comprehension of their mechanistic involvement. By doing so, it endeavors to propel forward the exploration of exosomal ncRNAs in TC, ultimately paving the way for innovative diagnostic and therapeutic strategies predicated on exosomes and their ncRNA content.

Liver injury during arsenic treatment for acute promyelocytic leukemia was previously reported in adults, but not comprehensively in children until now. This study aims to investigate liver injury in pediatric patients with APL, changes in liver function during treatment, and compare the effects of Arsenic trioxide (ATO) and Realgar-Indigo naturalis formula (RIF) on liver function. One hundred and eighty-six patients with 3076 patient tests were analyzed, who were enrolled in the Chinese Children’s Leukemia Group (CCLG)-APL2016 Protocol database between November 2016 and November 2018 in 38 hospitals across China(ChiCTR-OIN-17011227). Twenty of 164 patients (12.2

Diabetic retinopathy (DR) is a common diabetic microvascular complication and the main cause of vision loss in working-aged people. The NLRP3 inflammasome is a cytosolic multimeric complex that plays a significant role in innate immunity. After sensing injury, the NLRP3 inflammasome induces inflammatory mediator secretion and triggers a form of inflammatory cell death known as pyroptosis. Studies over the past five years have shown increased expression of NLRP3 and related inflammatory mediators in vitreous samples from DR patients at different clinical stages. Many NLRP3-targeted inhibitors have shown great antiangiogenic and antiinflammatory effects in diabetes mellitus models, suggesting that the NLRP3 inflammasome is involved in the progression of DR. This review covers the molecular mechanisms of NLRP3 inflammasome activation. Furthermore, we discuss the implications of the NLRP3 inflammasome in DR, including the induction of pyroptosis and inflammation and the promotion of microangiopathy and retinal neurodegeneration. We also summarize the research progress on targeting the NLRP3 inflammasome in DR therapeutics with the expectation of providing new insights into DR progression and treatment.

Osteoarthritis (OA) is one of the most common chronic joint diseases and is gradually becoming the main cause of disability and joint pain in the elderly worldwide. Pyroptosis is a regulated programmed cell death triggered by inflammasomes. It leads to cell swelling, lysis, and bioactive molecule secretion. Studies found that the damaged chondrocytes in OA joints had morphological characteristics of pyroptosis, and the cytokines associated with pyroptosis in synovial fluid increased, indicating that pyroptosis may have certain impacts on the pathological progression of OA. This review briefly summarizes the molecular mechanisms of pyroptosis and the epidemiology and pathogenesis of OA. Furthermore, we discussed the role of pyroptosis in articular cartilage and synovium during OA and reviewed the progress of pyroptosis-related molecules in the targeted therapy of OA joints, hoping to provide feasible directions for the diversified treatment of OA.

Bias in healthcare negatively impacts disparities in care, treatment, and outcomes, especially among minority populations. A scoping review of the literature was performed to provide a deeper understanding of how bias influences musculoskeletal pain and potential effects of bias-targeted interventions on reducing pain disparities, as well as identify gaps and make suggestions for further research in this area. Publications from peer-reviewed journals were searched using the databases PubMed/MEDLINE, PsycINFO, CINAHL, and Scopus, with 18 studies identified. The literature review revealed that clinician-based bias and discrimination worsen pain and disability by reducing access to treatment and increasing patient pain-related injustice, catastrophizing, depression, and perceived stress. In contrast, clinician education and perspective-taking, patient decision tools, and community outreach interventions can help reduce bias and disparities in musculoskeletal pain outcomes. Increasing the diversity of the healthcare workforce should also be a priority. Models of care focused on health equity may provide an ideal framework to reduce bias and provide sustainable improvement in musculoskeletal pain management.

Intervertebral disc degeneration (IDD), a progressive and multifactorial pathological process, is predominantly associated with low back pain and permanent disability. Pyroptosis is a type of lytic programmed cell death triggered by the activation of inflammasomes and caspases. Unlike apoptosis, pyroptosis is characterized by the rupture of the plasma membrane and the release of inflammatory mediators, accelerating the destruction of the extracellular matrix (ECM). Recent studies have shown that pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis in nucleus pulposus (NP) cells is activated in the progression of IDD. Furthermore, targeting pyroptosis in IDD demonstrates the excellent capacity of ECM remodeling and its anti-inflammatory properties, suggesting that pyroptosis is involved in the IDD process. In this review, we briefly summarize the molecular mechanism of pyroptosis and the pathogenesis of IDD. We also focus on the role of pyroptosis in the pathological progress of IDD and its targeted therapeutic application.

Introduction Yoga has been shown to reduce pain and improve function in populations with chronic low back pain (cLBP), yet the underlying molecular mechanisms remain elusive. This study examined the feasibility and acceptability of a yoga research protocol, including recruitment, retention, and data collection, and investigated the preliminary effects of yoga on psychological and neurophysiological functions, including gene expression and DNA methylation profiles, in participants with cLBP. Methods A one-arm trial was conducted with 11 participants with cLBP who enrolled in a 12-week yoga intervention. Data on subjective pain characteristics, quantitative sensory testing, and blood for analysis of differentially expressed genes and CpG methylation was collected prior to the start of the intervention and at study completion. Results Based on pre-determined feasibility and acceptability criteria, the yoga intervention was found to be feasible and highly acceptable to participants. There was a reduction in pain severity, interference, and mechanical pain sensitivity post-yoga and an increase in emotion regulation and self-efficacy. No adverse reactions were reported. Differential expression analysis demonstrated that the yoga intervention induced increased expression of antisense genes, some of which serve as antisense to known pain genes. In addition, there were 33 differentially hypomethylated positions after yoga (log2 fold change ≥ 1), with enrichment of genes involved in NIK/NF-kB signaling, a major pathway that modulates immune function and inflammation. Discussion/conclusions The study supports the feasibility and acceptability of the proposed protocol to test a specific mechanism of action for yoga in individuals with cLBP. These results also support the notion that yoga may operate through our identified psychological and neurophysiologic pathways to influence reduced pain severity and interference.

BACKGROUND:Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. METHODS:Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade. RESULTS:A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. CONCLUSION:The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.

Mental health conditions ranging from minor depressive symptoms to major depression, loneliness and poor quality of life are significant concerns in long-term care communities. Reminiscence is one intervention that has shown to reduce depressive symptoms and improve quality of life. The purpose of this scoping review was to determine the extent of reminiscence research undertaken in long-term care communities. Arksley and O'Malley's six stage method provided the framework for the review. Studies published in peer reviewed literature were identified based on searches in three databases (CINAHL, PUBMED, PsycINFO). Thirty-two studies met inclusion criteria. Of the 32 articles examined, 2 studies were conducted in the United States. Twenty-five health outcomes were examined, including twenty-three psychological outcomes and two physiological outcomes. Depression and cognitive functions were the most frequently measured outcomes. Lack of theoretical frameworks underpinning the studies, inadequate sample sizes, and weak methodology were noted in this review. Recommendations for future reminiscence research in long-term care communities are discussed.

OBJECTIVE:To synthesize the impact of health literacy on pain self-management contexts, processes, and outcomes. METHODS:This systematic review employed a narrative synthesis. We used databases, including PubMed and PsycINFO, and handsearching of the reference lists to identify articles published before December 2020. Pain self-management variables were chosen based on the Individual and Family Self-Management Theory. Quality was assessed using the National Institute of Health quality assessment tool for observational and cross-sectional studies. RESULTS:Twenty studies that included 6173 participants were used. Most studies measured functional domains of the health literacy concept. Twelve studies reported small to large associations between health literacy and pain knowledge, medication regimen adherence, or pain. Thirteen studies considered health literacy clinical risks in tailoring education, while seven viewed it as personal assets developed via education. CONCLUSIONS:Limited information on the contribution of health literacy to pain self-management context factors and processes exists. Current evidence was limited by a lack of temporality, theoretical basis, and a priori sample estimation. PRACTICE IMPLICATIONS:Using brief functional literacy scales in the clinical environment can be more practical. Identifying patients' literacy levels helps clinicians personalize education, which then promotes patients' knowledge of pain, medication regimen adherence, and pain control.