Change of function and brain activity in patients of right spastic arm paralysis combined with aphasia after contralateral cervical seventh nerve transfer surgery.

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.

Methylcellulose improves dissociation quality of adult human primary cardiomyocytes.

Obtaining high-quality adult human primary cardiomyocytes (hPCM) have been technically challenging due to isolation-induced biochemical and mechanical stress. Building upon a previous tissue slicing-assisted digestion method, we introduced polymers into the digestion solution to reduce mechanical damage to cells. We found that low-viscosity methylcellulose (MC) significantly improved hPCM viability and yield. Mechanistically, it protected cells from membrane damage, which led to decreased apoptosis and mitochondrial reactive oxygen species production. MC also improved the electrophysiological properties of hPCMs by maintaining the density of sodium channels. The effects on cell viability and cell yield effects were not recapitulated by MC of larger viscosities, other cellulose derivatives, nor shear protectants polyethylene glycol and polyvinyl alcohol. Finally, MC also enhanced the isolation efficiency and the culture quality of hPCMs from diseased ventricular myocardium, expanding its potential applications. Our findings showed that the isolation quality of hPCMs can be further improved through the addition of a polymer, rendering hPCMs a more reliable cellular model for cardiac research.

Prediction models for amputation after diabetic foot: systematic review and critical appraisal.

BACKGROUND: Numerous studies have developed or validated prediction models aimed at estimating the likelihood of amputation in diabetic foot (DF) patients. However, the quality and applicability of these models in clinical practice and future research remain uncertain. This study conducts a systematic review and assessment of the risk of bias and applicability of amputation prediction models among individuals with DF. METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, EBSCO CINAHL Plus, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedical Literature Database (CBM), and Weipu (VIP) from their inception to December 24, 2023. Two investigators independently screened the literature and extracted data using the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies. The Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist was employed to evaluate both the risk of bias and applicability. RESULTS: A total of 20 studies were included in this analysis, comprising 17 development studies and three validation studies, encompassing 20 prediction models and 11 classification systems. The incidence of amputation in patients with DF ranged from 5.9 to 58.5%. Machine learning-based methods were employed in more than half of the studies. The reported area under the curve (AUC) varied from 0.560 to 0.939. Independent predictors consistently identified by multivariate models included age, gender, HbA1c, hemoglobin, white blood cell count, low-density lipoprotein cholesterol, diabetes duration, and Wagner's Classification. All studies were found to exhibit a high risk of bias, primarily attributed to inadequate handling of outcome events and missing data, lack of model performance assessment, and overfitting. CONCLUSIONS: The assessment using PROBAST revealed a notable risk of bias in the existing prediction models for amputation in patients with DF. It is imperative for future studies to concentrate on enhancing the robustness of current prediction models or constructing new models with stringent methodologies.

Unraveling Estrogen and PCSK9's Roles in Lipid Metabolism Disorders among Ovariectomized Mice.

We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein receptor levels. Utilizing both animal and cellular models, including ovariectomized mice and HepG2 cell lines, we demonstrate that estrogen deficiency leads to a disruption in lipid metabolism, characterized by elevated levels of total cholesterol and LDL-C. The study commences with mice undergoing ovariectomy, followed by a diet regimen comprising either high-fat diet or normal feed for a four-week duration. Key assessments include analyzing lipid metabolism, measuring PCSK9 levels in the bloodstream, and evaluating hepatic low-density lipoprotein receptor expression. We will also conduct correlation analyses to understand the relationship between PCSK9 and various lipid profiles. Further, a subset of ovariectomized mice on high-fat diet will undergo treatment with either estrogen or PCSK9 inhibitor for two weeks, with a subsequent re-evaluation of the earlier mentioned parameters. Our findings reveal that estrogen inhibits PCSK9-mediated degradation of low-density lipoprotein receptor, a process crucial for maintaining lipid homeostasis. Through a series of experiments, including immunohistochemistry and western blot analysis, we establish that PCSK9 is involved in lipid metabolism disorders caused by estrogen deficiency and that estrogen regulates PCSK9 and low-density lipoprotein receptor at post-transcriptional level. The study provides a mechanism for the involvement of PCSK9 in elucidating the disorders of lipid metabolism caused by estrogen deficiency due to perimenopause and ovarian decline.

Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice.

OBJECTIVES: The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm) mice. METHODS: The CthΔskm mice and littermate Cth-floxed (Cthf/f) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle. RESULTS: Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cthf/f mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm+HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm+HFD mice compared to Cthf/f+HFD mice. DISCUSSION: Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.

The recent advancements in protein nanoparticles for immunotherapy.

In recent years, the advancement of nanoparticle-based immunotherapy has introduced an innovative strategy for combatting diseases. Compared with other types of nanoparticles, protein nanoparticles have obtained substantial attention owing to their remarkable biocompatibility, biodegradability, ease of modification, and finely designed spatial structures. Nature provides several protein nanoparticle platforms, including viral capsids, ferritin, and albumin, which hold significant potential for disease treatment. These naturally occurring protein nanoparticles not only serve as effective drug delivery platforms but also augment antigen delivery and targeting capabilities through techniques like genetic modification and covalent conjugation. Motivated by nature's originality and driven by progress in computational methodologies, scientists have crafted numerous protein nanoparticles with intricate assembly structures, showing significant potential in the development of multivalent vaccines. Consequently, both naturally occurring and de novo designed protein nanoparticles are anticipated to enhance the effectiveness of immunotherapy. This review consolidates the advancements in protein nanoparticles for immunotherapy across diseases including cancer and other diseases like influenza, pneumonia, and hepatitis.

Advances in therapeutic cancer vaccines: Harnessing immune adjuvants for enhanced efficacy and future perspectives.

Preventive cancer vaccines are highly effective in preventing viral infection-induced cancer, but advances in therapeutic cancer vaccines with a focus on eliminating cancer cells through immunotherapy are limited. To develop therapeutic cancer vaccines, the integration of optimal adjuvants is a potential strategy to enhance or complement existing therapeutic approaches. However, conventional adjuvants do not satisfy the criteria of clinical trials for therapeutic cancer vaccines. To improve the effects of adjuvants in therapeutic cancer vaccines, effective vaccination strategies must be formulated and novel adjuvants must be identified. This review offers an overview of the current advancements in therapeutic cancer vaccines and highlights in situ vaccination approaches that can be synergistically combined with other immunotherapies by harnessing the adjuvant effects. Additionally, the refinement of adjuvant systems using cutting-edge technologies and the elucidation of molecular mechanisms underlying immunogenic cell death to facilitate the development of innovative adjuvants have been discussed.

Incidence of dreaming during ciprofol anesthesia for painless gastroscopy.

BACKGROUND: Dreaming is often reported by patients who undergo propofol-based sedation, but there have not been any studies to date focused on the incidence of dreaming and factors associated therewith following the administration of ciprofol anesthesia in patients undergoing painless gastroscopy. The present study was thus developed with the goal of assessing the incidence of dreaming. METHODS: In total, this study enrolled 200 patients undergoing painless gastroscopy. During the procedure, patients' electroencephalographic Bispectral Index (BIS), blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO2), and PETCO2 were monitored. When their MOAA/S score reached five after the procedure, patients were administered questionnaires including the Brice questionnaire and a five-point Likert Scale, and the content of any recalled dreams was also recorded. RESULTS: Overall, 27.5% of the participants in this study reported dreaming during the procedure, with most having experienced simple, pleasant dreams about everyday life. Identified predictors of dreaming during painless gastroscopy included lower ASA grade, preoperative knowledge of painless examination, a higher frequency of dreams in the month before the procedure, poor sleep quality during the month before the procedure, and shorter awakening time. Dreamers showed significantly lower BIS values at 2 min after endoscope insertion and following endoscope removal, and also showed lower minimum BIS values compared with non-dreamers. CONCLUSIONS: The postoperative dream recall incidence in this study was 27.5% among patients undergoing painless gastroscopy under ciprofol sedation anesthesia.

Pembrolizumab in patients from China with microsatellite instability-high/mismatch repair deficient tumors: KEYNOTE-158.

Aim: To evaluate pembrolizumab in patients of Chinese descent with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors enrolled in KEYNOTE-158 (Cohort L). Methods: Patients with MSI-H/dMMR advanced tumors received pembrolizumab 200 mg IV Q3W. Primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: 24 patients were enrolled (20 were evaluable for efficacy). With median follow-up of 12.4 months, the ORR was 70%. DOR, PFS and OS were all not reached. A total of 19 (79%) patients had a treatment-related adverse event (AE; grade ≥3 in 4 [17%]), and 8 (33%) had an immune-mediated AE (grade ≥3 in (4 [17%]). Conclusion: Pembrolizumab provided meaningful and durable responses with manageable safety. These results are consistent with those reported for the global trial.

Discovery of potent PROTAC degraders of Pin1 for the treatment of acute myeloid leukemia.

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is overexpressed and/or overactivated in many human cancers and has been shown to play a critical role during oncogenesis. Despite the potential of Pin1 as a drug target, its successful targeting has proved to be challenging. We speculate that only blocking the enzymatic function of Pin1 with inhibitors may not be sufficient to lead to a total loss-of-function. Here, we report the discovery of P1D-34, a first-in-class and potent PROTAC degrader of Pin1, which induced Pin1 degradation with a DC50 value of 177 nM and exhibited potent degradation-dependent anti-proliferative activities in a panel of acute myeloid leukemia (AML) cell lines. In contrast, Pin1 inhibitor Sulfopin did not show activity. More significantly, P1D-34 could sensitize Bcl-2 inhibitor ABT-199 in Bcl-2 inhibitor-resistant AML cells, highlighting the potential therapeutic value of targeted Pin1 degradation for Bcl-2 inhibitor-resistant AML treatment. Further mechanism study revealed that P1D-34 led to the up-regulation of ROS pathway and down-regulation of UPR pathway to induce cell DNA damage and apoptosis. Notably, we further demonstrated that treatment with the combination formula of glucose metabolism inhibitor 2-DG and P1D-34 led to a notable synergistic anti-proliferative effect, further expanding its applicability. These data clearly reveal the practicality and importance of PROTAC as a preliminary tool compound suitable for assessment of Pin1-dependent pharmacology and a promising strategy for AML treatment.

Distinct cellular microenvironment with cytotypic effects regulates orderly regeneration of vascular tissues.

Regeneration of the architecturally complex blood vascular system requires precise temporal and spatial control of cell behaviours. Additional components must be integrated into the structure to achieve clinical success for in situ tissue engineering. Consequently, this study proposed a universal method for including any substrate type in vascular cell extracellular matrices (VCEM) via regulating selective adhesion to promote vascular tissue regeneration. The results uncovered that the VCEM worked as cell adhesion substrates, exhibited cell type specificity, and functioned as an address signal for recognition by vascular cells, which resulted in matching with the determined cells. The qPCR and immunofluorescence results revealed that a cell type-specific VCEM could be designed to promote or inhibit cell adhesion, consistenting with the expression patterns of eyes absent 3 (Eya3). In addition, a 3D vascular graft combined with VCEM which could recapitulate the vascular cell-like microenvironment was fabricated. The vascular graft revealed a prospective role for cellular microenvironment in the establishment of vascular cell distribution and tissue architecture, and potentiated the orderly regeneration and functional recovery of vascular tissues in vivo. The findings demonstrate that differential adhesion between cell types due to the cellular microenvironment is sufficient to drive the complex assembly of engineered blood vessel functional units, and underlies hierarchical organization during vascular regeneration.

Adipose tissue reconstruction facilitated with low immunogenicity decellularized adipose tissue scaffolds.

There is currently an urgent need to develop engineered scaffolds to support new adipose tissue formation and facilitate long-term maintenance of function and defect repair to further generate prospective bioactive filler materials capable of fulfilling surgical needs. Herein, adipose regeneration methods were optimized and decellularized adipose tissue (DAT) scaffolds with good biocompatibility were fabricated. Adipose-like tissues were reconstructed using the DAT and 3T3-L1 preadipocytes, which have certain differentiation potential, and the regenerative effects of the engineered adipose tissuesin vitroandin vivowere explored. The method improved the efficiency of adipose removal from tissues, and significantly shortened the time for degreasing. Thus, the DAT not only provided a suitable space for cell growth but also promoted the proliferation, migration, and differentiation of preadipocytes within it. Following implantation of the constructed adipose tissuesin vivo, the DAT showed gradual degradation and integration with surrounding tissues, accompanied by the generation of new adipose tissue analogs. Overall, the combination of adipose-derived extracellular matrix and preadipocytes for adipose tissue reconstruction will be of benefit in the artificial construction of biomimetic implant structures for adipose tissue reconstruction, providing a practical guideline for the initial integration of adipose tissue engineering into clinical medicine.

Establishment of a risk prediction model for bowel preparation failure prior to colonoscopy.

BACKGROUND: This study aimed to determine the factors that contribute to the failure of bowel preparation in patients undergoing colonoscopy and to develop a risk prediction model. METHODS: A total of 1115 outpatients were included. Patients were randomly divided into two groups: the modeling group (669 patients) and the validation group (446 patients). In the modeling group, patients were further divided into two groups based on their success and failure in bowel preparation using the Boston Bowel Preparation Scale. A logistic regression analysis model was used to determine the risk factors of bowel preparation failure, which was subsequently visualized using an alignment diagram. RESULTS: After controlling for relevant confounders, multifactorial logistic regression results showed that age ≥ 60 years (OR = 2.246), male (OR = 2.449), body mass index ≥ 24 (OR = 2.311), smoking (OR = 2.467), chronic constipation (OR = 5.199), diabetes mellitus (OR = 5.396) and history of colorectal surgery (OR = 5.170) were influencing factors of bowel preparation failure. The area under the ROC curve was 0.732 in the modeling group and 0.713 in the validation group. According to the calibration plot, the predictive effect of the model and the actual results were in good agreement. CONCLUSIONS: Age ≥ 60 years, male, body mass index ≥ 24, smoking, chronic constipation, diabetes mellitus, and history of colorectal surgery are independent risk factors for bowel preparation failure. The established prediction model has a good predictive efficacy and can be used as a simple and effective tool for screening patients at high risk for bowel preparation failure.

tiRNA-Gly-GCC-001 in major depressive disorder: Promising diagnostic and therapeutic biomarker.

BACKGROUND AND PURPOSE: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA-derived small ribonucleic acids (tsRNAs) have been established as promising non-invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development. EXPERIMENTAL APPROACH: Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA-Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed. KEY RESULTS: In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up-regulated and 4 down-regulated). qRT-PCR was used to validate the expression of six tsRNAs that were up-regulated in MDD (tiRNA-1:20-chrM.Ser-GCT, tiRNA-1:33-Gly-GCC-1, tRF-1:22-chrM.Ser-GCT, tRF-1:31-Ala-AGC-4-M6, tRF-1:31-Pro-TGG-2 and tRF-1:32-chrM.Gln-TTG). Interestingly, serum tiRNA-Gly-GCC-001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA-Gly-GCC-001 is predicted to suppress brain-derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA-Gly-GCC-001 down-regulation was evident following an 8-week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy. CONCLUSION AND IMPLICATIONS: Our current work reports for the first time that tiRNA-Gly-GCC-001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy.

ANKRD22 promotes resolution of psoriasiform skin inflammation by antagonizing NIK-mediated IL-23 production.

Inflammation resolution is an essential process for preventing the development of chronic inflammatory diseases. However, the mechanisms that regulate inflammation resolution in psoriasis are not well understood. Here, we report that ANKRD22 is an endogenous negative orchestrator of psoriasiform inflammation because ANKRD22-deficient mice are more susceptible to IMQ-induced psoriasiform inflammation. Mechanistically, ANKRD22 deficiency leads to excessive activation of the TNFRII-NIK-mediated noncanonical NF-κB signaling pathway, resulting in the hyperproduction of IL-23 in DCs. This is due to ANKRD22 being a negative feedback regulator for NIK because it physically binds to and assists in the degradation of accumulated NIK. Clinically, ANKRD22 is negatively associated with IL-23A expression and psoriasis severity. Of greater significance, subcutaneous administration of an AAV carrying ANKRD22-overexpression vector effectively hastens the resolution of psoriasiform skin inflammation. Our findings suggest ANKRD22, an endogenous supervisor of NIK, is responsible for inflammation resolution in psoriasis, and may be explored in the context of psoriasis therapy.

Neuroprotective effects of a novel peptide through the Rho-integrin-Tie2 and PI3K/Akt pathways in experimental autoimmune encephalomyelitis model.

Purpose: The interaction between inflammatory cells and integrin in the endothelium plays a key role during infiltration. Previous evidence has shown that synthetic C16 peptide selectively binds to integrins αvß3 and α5ß1 and exhibits a neuroprotective effect. It has also been reported to inhibit the differentiation of microglia into the M1 (pro-inflammatory) phenotype while promoting its differentiation to the M2 (anti-inflammatory) phenotype. This study aimed to investigate the mechanisms of action of the C16 peptide in multiple sclerosis using a rodent model. Methods: Molecular, morphological, and neurophysiological assays were used to investigate the neuroprotective effects of C16 peptide and related signaling pathways in a model of EAE. Results: The results showed that C16 significantly improved the clinical score and cortical somatosensory/motor evoked potential. It also alleviated inflammatory responses, including microglial activation and leukocyte infiltration, relieved the impairment of the brain blood barrier and edema, and reduced neuronal apoptosis, axonal loss, and demyelination induced by EAE. The C16 peptide increased the expressions of pTie-2 and Tie-2, integrin αvß3, and α5ß1 and activated the PI3K/Akt signal pathway but decreased the expression of Rho. Co-treatment of C16 with Tie-2 inhibitor and PI3K inhibitor LY294002 attenuated these effects of C16. Conclusion: The C16 peptide demonstrated neuroprotection in the EAE model through the integrin, Tie-2, and PI3K/Akt signaling pathways, and it could be a potential strategy for treating inflammation-related diseases in the central nervous system.

Deciphering PDH1's role in mung bean domestication: a genomic perspective on pod dehiscence.

Mung bean (Vigna radiata) stands as a crucial legume crop in Asia, contributing to food security. However, our understanding of the underlying genetic foundation governing domesticated agronomic traits, especially those linked to pod architecture, remains largely unexplored. In this study, we delved into the genomic divergence between wild and domesticated mung bean varieties, leveraging germplasm obtained from diverse sources. Our findings unveiled pronounced variation in promoter regions (35%) between the two mung bean subpopulations, suggesting substantial changes in gene expression patterns during domestication. Leveraging transcriptome analysis using distinct reproductive stage pods and subpopulations, we identified candidate genes responsible for pod and seed architecture development, along with Genome-Wide Association Studies (GWAS) and Quantitative Trait Locus (QTL) analysis. Notably, our research conclusively confirmed PDH1 as a parallel domesticated gene governing pod dehiscence in legumes. This study imparts valuable insights into the genetic underpinnings of domesticated agronomic traits in mung bean, and simultaneously highlighting the parallel domestication of pivotal traits within the realm of legume crops.

The regulatory role of CD36 in hematopoiesis beyond fatty acid uptake.

CD36 is a transmembrane glycoprotein, located on surface of numerous cell types. This review is aimed to explore regulatory role of CD36 in hematopoiesis beyond fatty acid uptake. CD36 acts as a pattern recognition receptor, regulates cellular fatty acid homeostasis, and negatively monitors angiogenesis. CD36 also mediates free fatty acid transportation to hematopoietic stem cells in response to infections. During normal physiology and pathophysiology, CD36 significantly participates in the activation and metabolic needs of platelets, macrophages, monocytes, T cells, B cells, and dendritic cells. CD36 has shown a unique relationship with Plasmodium falciparum-infected erythrocytes (PfIEs) as a beneficiary for both parasite and host. CD36 actively participates in pathogenesis of various hematological cancers as a significant prognostic biomarker including AML, HL, and NHL. CD36-targeting antibodies, CD36 antagonists (small molecules), and CD36 expression inhibitors/modulators are used to target CD36, depicting its therapeutic potential. Many preclinical studies or clinical trials were performed to assess CD36 as a therapeutic target; some are still under investigation. This review reflects the role of CD36 in hematopoiesis which requires more consideration in future research.

Anti-Toxoplasma gondii antibodies as a risk factor for the prevalence and severity of systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. METHODS: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. RESULTS: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70-3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14-2.70, P = 0.011) compared to ATxA-IgG- patients. Relative to ATxA-IgG- patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. CONCLUSIONS: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations.

AEBP1 promotes papillary thyroid cancer progression by activating BMP4 signaling.

Papillary thyroid cancer (PTC) is the most prevalent endocrine cancer worldwide. Approximately 30 % of PTC patients will progress into the advanced or metastatic stage and have a relatively poor prognosis. It is well known that epithelial-mesenchymal transition (EMT) plays a pivotal role in thyroid cancer metastasis, resistance to therapy, and recurrence. Clarifying the molecular mechanisms of EMT in PTC progression will help develop the targeted therapy of PTC. The aberrant expression of some transcription factors (TFs) participated in many pathological processes of cancers including EMT. In this study, by performing bioinformatics analysis, adipocyte enhancer-binding protein 1 (AEBP1) was screened as a pivotal TF that promoted EMT and tumor progression in PTC. In vitro experiments indicated that knockout of AEBP1 can inhibit the growth and invasion of PTC cells and reduce the expression of EMT markers including N-cadherin, TWIST1, and ZEB2. In the xenograft model, knockout of AEBP1 inhibited the growth and lung metastasis of PTC cells. By performing RNA-sequencing, dual-luciferase reporter assay, and chromatin immunoprecipitation assay, Bone morphogenetic protein 4 (BMP4) was identified as a downstream target of AEBP1. Over-expression of BMP4 can rescue the inhibitory effects of AEBP1 knockout on the growth, invasion, and EMT phenotype of PTC cells. In conclusion, these findings demonstrated that AEBP1 plays a critical role in PTC progression by regulating BMP4 expression and the AEBP1-BMP4 axis may present novel therapeutic targets for PTC treatment.