A comprehensive review of the anticancer effects of decursin.

Cancer is a globally complex disease with a plethora of genetic, physiological, metabolic, and environmental variations. With the increasing resistance to current anticancer drugs, efforts have been made to develop effective cancer treatments. Currently, natural products are considered promising cancer therapeutic agents due to their potent anticancer activity and low intrinsic toxicity. Decursin, a coumarin analog mainly derived from the roots of the medicinal plant Angelica sinensis, has a wide range of biological activities, including anti-inflammatory, antioxidant, neuroprotective, and especially anticancer activities. Existing studies indicate that decursin affects cell proliferation, apoptosis, autophagy, angiogenesis, and metastasis. It also indirectly affects the immune microenvironment and can act as a potential anticancer agent. Decursin can exert synergistic antitumor effects when used in combination with a number of common clinical anticancer drugs, enhancing chemotherapy sensitivity and reversing drug resistance in cancer cells, suggesting that decursin is a good drug combination. Second, decursin is also a promising lead compound, and compounds modifying its structure and formulation form also have good anticancer effects. In addition, decursin is not only a key ingredient in several natural herbs and dietary supplements but is also available through a biosynthetic pathway, with anticancer properties and a high degree of safety in cells, animals, and humans. Thus, it is evident that decursin is a promising natural compound, and its great potential for cancer prevention and treatment needs to be studied and explored in greater depth to support its move from the laboratory to the clinic.

Lower limit characterization of segregation degree for large-size low-alloy steel.

Based on the original position statistic distribution analysis technique, the characterization method of segregation for large-size metal materials gives significant guidance to the research of material properties and production. However, random errors are inevitably brought into the calculation of segregation degree for materials characterization by the Spark Mapping Analysis for Large Sample (SMALS) technique, resulting in a misguide of the segregation degree. In this paper, we present the lower limit of segregation degree (Ds(L)) method to distinguish the random error from metal material segregation for large-size samples over the SMALS method. The random error of standard material in the 95% confidence interval was utilized as Ds(L) and the method has been applied for macro-segregation quantitative analysis. The precision correlation between Spark Atomic Emission Spectrometry (Spark-AES) and SMALS was established. Furthermore, the functional relationship between the Ds(L) and element content C can be obtained in the SMALS method. The Ds(L) method as the criterion can be used to not only characterize the minimum limit of the segregation degree but also the segregation existence for large-size samples. Applying to low-alloy steel can illustrate the effective performance of the Ds(L) method. Results on both spark mapping analysis and Spark-AES verify the substantial consistency.

Obesity alters immunopathology in cancers and inflammatory diseases.

Obesity is characterized by chronic low-grade inflammation and is strongly associated with multiple immunological diseases, including cancer and inflammatory diseases. Recent animal studies revealed that obesity-induced immunological changes worsen immune-driven diseases and cause resistance to immunotherapy. Here, we discuss the role of obesity in the immunopathology and treatment responses of cancers, respiratory and allergic diseases, and IL-17-mediated inflammatory diseases. We summarize the unique features of the inflammatory state of these diseases, which are orchestrated by obesity. In particular, obesity alters the immune landscape in cancers with a reprogrammed metabolic profile of tumor-infiltrating immune cells. Obesity exacerbates airway inflammation by dysregulating multiple immune-cell subsets. Obesity also dysregulates Th17, IL-17-producing mucosal-associated invariant T (MAIT), and γδ T cells, which contribute to IL-17-mediated inflammatory response in multiple sclerosis, inflammatory bowel disease, psoriasis, atopic dermatitis, and rheumatoid arthritis. By identifying the effects of obesity on immunological diseases, new strategies could be devised to target immune dysregulation caused by obesity.

Analysis of Ti-inclusions in high carbon chromium bearing steel by laser-induced breakdown spectroscopy.

The presence of Ti-inclusions has a significant impact on the fatigue life of bearing steel. Laser-induced breakdown spectroscopy (LIBS) is a useful tool for analyzing Ti-inclusions, despite the fact that the effective excitation area of LIBS is actually larger than the pre-set spot diameter. The area affected by the LIBS spot ranges from 150 µm to 376.6 µm. A new parameter L has been introduced for better understanding the characterization of Ti-inclusions detected in SEM-EDS and LIBS measurements, When the L threshold falls below the value of 188.3 µm, the SEM-EDS and LIBS data are obtained from the same Ti-inclusion. The study demonstrates that there is a linear relationship between LIBS intensity and Ti-inclusions area, which was tested both theoretically and practically. The analysis of six samples of rolling GCr15 bearing steel with a Cr element content of 1.5% shows that one regression line is enough for analyzing the same type of inclusion processed under the same conditions. This method can significantly reduce the workload and analysis time during the actual analysis process.

Chaetocin exhibits anticancer effects in esophageal squamous cell carcinoma via activation of Hippo pathway.

Dysfunction of the Hippo pathway is common in esophageal squamous carcinoma (ESCC). Chaetocin, a small molecular compound isolated from the marine fungus, exhibits potent anticancer effects. However, the anticancer effects of chaetocin on ESCC and its potential relationship to Hippo pathway remain unclear. Here, we demonstrated that chaetocin dramatically inhibited the proliferation in ESCC cells by causing cycle arrest in the M phase and activating the caspase-dependent apoptosis signaling pathway in vitro, and we also found that chaetocin induced the accumulation cellular reactive oxygen species (ROS). The RNA-seq analysis indicated that the Hippo pathway is one of the most enriched pathways after chaetocin treatment. We further revealed that chaetocin triggered the activation of Hippo pathway in ESCC cells, which is characterized by elevated phosphorylation levels of almost all core proteins in Hippo pathway, such as MST1 (Thr183), MST2 (Thr180), MOB1 (Thr35), LAST1 (Thr1079 and Ser909) and YAP (Ser127), ultimately leading to decreased nuclear translocation of YAP. Moreover, the MST1/2 inhibitor XMU-MP-1 not only partially rescued the inhibitory effect chaetocin-induced proliferation, but also rescued the chaetocin-induced apoptosis in ESCC cells. Furthermore, in vivo results confirmed the antitumor effect of chaetocin and its relationship with Hippo pathway. Taken together, our study demonstrates that chaetocin exhibits anticancer effects in ESCC via activation of Hippo pathway. These results provide an important basis for further research of chaetocin as a potential candidate for ESCC treatment.

Advances in holliday junction recognition protein (HJURP): Structure, molecular functions, and roles in cancer.

Oncogenes are increasingly recognized as important factors in the development and progression of cancer. Holliday Junction Recognition Protein (HJURP) is a highly specialized mitogenic protein that is a chaperone protein of histone H3. The HJURP gene is located on chromosome 2q37.1 and is involved in nucleosome composition in the mitotic region, forming a three-dimensional crystal structure with Centromere Protein A (CENP-A) and the histone 4 complex. HJURP is involved in the recruitment and assembly of centromere and kinetochore and plays a key role in stabilizing the chromosome structure of tumor cells, and its dysfunction may contribute to tumorigenesis. In the available studies HJURP is upregulated in a variety of cancer tissues and cancer cell lines and is involved in tumor proliferation, invasion, metastasis and immune response. In an in vivo model, overexpression of HJURP in most cancer cell lines promotes cell proliferation and invasiveness, reduces susceptibility to apoptosis, and promotes tumor growth. In addition, upregulation of HJURP was associated with poorer prognosis in a variety of cancers. These properties suggest that HJURP may be a possible target for the treatment of certain cancers. Various studies targeting HJURP as a prognostic and therapeutic target for cancer are gradually attracting interest and attention. This paper reviews the functional and molecular mechanisms of HJURP in a variety of tumor types with the aim of providing new targets for future cancer therapy.

Sputum pathogen spectrum and clinical outcomes of upper respiratory tract infection in bronchiectasis exacerbation: a prospective cohort study.

Upper respiratory tract infection (URTI) is common in humans. We sought to profile sputum pathogen spectrum and impact of URTI on acute exacerbation of bronchiectasis (AE). Between March 2017 and December 2021, we prospectively collected sputum from adults with bronchiectasis. We stratified AEs into events related (URTI-AE) and unrelated to URTI (non-URTI-AE). We captured URTI without onset of AE (URTI-non-AE). We did bacterial culture and viral detection with polymerase chain reaction, and explored the pathogen spectrum and clinical impacts of URTI-AE via longitudinal follow-up. Finally, we collected 479 non-AE samples (113 collected at URTI-non-AE and 225 collected at clinically stable) and 170 AE samples (89 collected at URTI-AE and 81 collect at non-URTI-AE). The viral detection rate was significantly higher in URTI-AE (46.1%) than in non-URTI-AE (4.9%) and URTI-non-AE (11.5%) (both P < 0.01). Rhinovirus [odds ratio (OR): 5.00, 95% confidence interval (95%CI): 1.06-23.56, P = 0.03] detection was independently associated with URTI-AE compared with non-URTI-AE. URTI-AE tended to yield higher viral load and detection rate of rhinovirus, metapneumovirus and bacterial shifting compared with URTI-non-AE. URTI-AE was associated with higher initial viral loads (esp. rhinovirus, metapneumovirus), greater symptom burden (higher scores of three validated questionnaires) and prolonged recovery compared to those without. Having experienced URTI-AE predicted a greater risk of future URTI-AE (OR: 10.90, 95%CI: 3.60-33.05). In summary, URTI is associated with a distinct pathogen spectrum and aggravates bronchiectasis exacerbation, providing the scientific rationale for the prevention of URTI to hinder bronchiectasis progression.

Polyethylene glycol combined with lactulose has better efficacy than polyethylene glycol alone in bowel preparation before colonoscopy: A meta-analysis.

BACKGROUND: The accuracy of diagnosis and the safety of treatment in colonoscopy depends largely on the quality of bowel cleansing. This study aimed to compare the efficacy and adverse reactions of Polyethylene Glycol (PEG) combined with lactulose with that of PEG alone in bowel preparation before colonoscopy. METHODS: The authors searched a number of databases including EMBASE, MEDLINE, Cochrane Library, and China Academic Journals Full-text Database. The authors screened according to literature inclusion and exclusion criteria, assessed the quality of the included literature, and extracted the data. The meta-analysis of included literature used RevMan 5.3 and Stata 14.0 software. RESULTS: A total of 18 studies, including 2274 patients, were enrolled. The meta-analysis showed that PEG combined with lactulose had a better efficacy (OR = 3.87, 95% CI 3.07‒4.87, p = 0.000, and I2 = 36.2% in the efficiency group; WMD = 0.86, 95% CI 0.69‒1.03, p = 0.032 and I2 = 0% in the BBPS score group) in bowel preparation for patients with or without constipation. Moreover, PEG combined with lactulose had fewer adverse reactions, including abdominal pain (OR = 1.42, 95% CI 0.94‒2.14, p = 0.094), nausea (OR = 1.60, 95% CI 1.13‒2.28, p = 0.009) and vomiting (OR = 1.77, 95% CI 1.14‒2.74, p = 0.011), than PEG alone. No significant reduction in the incidence of abdominal distention was observed. CONCLUSION: PEG combined with lactulose may be a better choice for bowel preparation before colonoscopy compared with PEG alone.

Motile Ciliary Disorders of the Nasal Epithelium in Adults With Bronchiectasis.

BACKGROUND: Motile ciliary disorder (MCD) has been implicated in chronic inflammatory airway diseases such as asthma and COPD. RESEARCH QUESTION: What are the characteristics of MCD of the nasal epithelium and its association with disease severity and inflammatory endotypes in adults with bronchiectasis? STUDY DESIGN AND METHODS: In this observational study, we recruited 167 patients with bronchiectasis and 39 healthy control participants who underwent brushing of the nasal epithelium. A subgroup of patients underwent bronchoscopy for bronchial epithelium sampling (n = 13), elective surgery for bronchial epithelium biopsy (n = 18), and blood sampling for next-generation sequencing (n = 37). We characterized systemic and airway inflammatory endotypes in bronchiectasis. We conducted immunofluorescence assays to profile ultrastructural (dynein axonemal heavy chain 5 [DNAH5], dynein intermediate chain 1 [DNAI1], radial spoke head protein 9 [RSPH9]) and ciliogenesis marker expression (Ezrin). RESULTS: MCD was present in 89.8% of patients with bronchiectasis, 67.6% showed secondary MCD, and 16.2% showed primary plus secondary MCD. Compared with healthy control participants, patients with bronchiectasis yielded abnormal staining patterns of DNAH5, DNAI1, and RSPH9 (but not Ezrin) that were more prominent in moderate to severe bronchiectasis. MCD pattern scores largely were consistent between upper and lower airways and between large-to-medium and small airways in bronchiectasis. Coexisting nasal diseases and asthma did not confound nasal ciliary ultrastructural marker expression significantly. The propensity of MCD was unaffected by the airway or systemic inflammatory endotypes. MCD, particularly an ultrastructural abnormality, was notable in patients with mild bronchiectasis who showed blood or sputum eosinophilia. INTERPRETATION: Nasal ciliary markers profiling provides complimentary information to clinical endotyping of bronchiectasis.

Polyethylene glycol combined with lactulose has better efficacy than polyethylene glycol alone in bowel preparation before colonoscopy: A meta-analysis

Abstract Background: The accuracy of diagnosis and the safety of treatment in colonoscopy depends largely on the quality of bowel cleansing. This study aimed to compare the efficacy and adverse reactions of Polyethylene Glycol (PEG) combined with lactulose with that of PEG alone in bowel preparation before colonoscopy. Methods: The authors searched a number of databases including EMBASE, MEDLINE, Cochrane Library, and China Academic Journals Full-text Database. The authors screened according to literature inclusion and exclusion criteria, assessed the quality of the included literature, and extracted the data. The meta-analysis of included literature used RevMan 5.3 and Stata 14.0 software. Results: A total of 18 studies, including 2274 patients, were enrolled. The meta-analysis showed that PEG combined with lactulose had a better efficacy (OR = 3.87, 95% CI 3.07‒4.87, p = 0.000, and I2 = 36.2% in the efficiency group; WMD = 0.86, 95% CI 0.69‒1.03, p = 0.032 and I2 = 0% in the BBPS score group) in bowel preparation for patients with or without constipation. Moreover, PEG combined with lactulose had fewer adverse reactions, including abdominal pain (OR = 1.42, 95% CI 0.94‒2.14, p = 0.094), nausea (OR = 1.60, 95% CI 1.13‒2.28, p = 0.009) and vomiting (OR = 1.77, 95% CI 1.14‒2.74, p = 0.011), than PEG alone. No significant reduction in the incidence of abdominal distention was observed. Conclusion: PEG combined with lactulose may be a better choice for bowel preparation before colonoscopy compared with PEG alone.

Attenuated Salmonella Typhimurium with truncated LPS and outer membrane-displayed RGD peptide for cancer therapy.

Gram-negative, facultatively anaerobic bacteria Salmonella Typhimurium is a candidate agent or delivery vector for cancer therapy. Effective targeted therapies in addition to radiotherapy, chemotherapy and surgery have been urgently needed as an alternative or supplement. This study expected to further improve the tumor-targeting ability of Salmonella bacteria through genetic modifications. Based on an auxotrophic Salmonella bacterial strain (D2), we constructed Salmonella mutants with altered LPS length to facilitate displaying the RGD4C targeting peptide on the outer membrane surface of Salmonella. The expression of RGD4C peptide in fusion with OmpA was identified by outer membrane protein extraction and WB detection in different mutant strains. However, flow cytometry analysis following immunofluorescence staining demonstrated that the extracellular length of Salmonella LPS did affect the surface display of RGD4C peptide. The strain D2-RGD4C that synthesized intact LPS including lipid A, core oligosaccharides and O antigen polysaccharides could hardly display RGD4C peptide, showing the same fluorescence signal intensity as the strains not expressing RGD4C peptide. Among different strains, D2 ∆rfaJ-RGD4C that synthesized truncated LPS including lipid A and partial core oligosaccharides was capable of displaying RGD4C peptide most efficiently and showed the highest ability to target HUVECs expressing αV integrin and tumor tissue with abundant neovascularization. Animal experiments also demonstrated that this tumor-targeting attenuated Salmonella strain to simultaneously deliver endostatin and TRAIL, two agents with different anti-tumor activities, could significantly inhibit tumor growth and prolong mouse survival. Thus, our studies revealed that Salmonella could be genetically engineered to improve its tumor targeting via the truncation of LPS and surface display of targeting peptides, thereby eliciting superior anti-tumor effects through targeted delivery of drug molecules.

MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT.

BACKGROUND & AIMS: Excessive inflammatory responses and oxidative stress are considered the main characteristics of inflammatory bowel disease (IBD). Endogenous hydrogen sulfide (H2S) has been reported to show anti-inflammatory activity in IBD. The main aim of this study was to explore the role of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous H2S biosynthesis, in IBD. METHODS: Colonic MPST expression was evaluated in mice and patients with IBD. Various approaches were used to explore the concrete mechanism underlying MPST regulation of the progression of colitis through in vivo and in vitro models. RESULTS: MPST expression was markedly decreased in colonic samples from patients with ulcerative colitis (UC) or Crohn's disease (CD) and from mice treated with DSS. MPST deficiency significantly aggravated the symptoms of murine colitis, exacerbated inflammatory responses and apoptosis, and inhibited epithelium stem cell-derived organoid formation in an H2S-independent manner. Consistently, when HT29 cells were treated with TNF-α, inhibition of MPST significantly increased the expression of proinflammatory cytokines, the amount of ROS and the prevalence of apoptosis, whereas overexpression of MPST markedly improved these effects. RNA-seq analysis showed that MPST might play a role in regulating apoptosis through AKT signaling. Mechanistically, MPST directly interacted with AKT and reduced the phosphorylation of AKT. Additionally, MPST expression was positively correlated with AKT expression in human IBD samples. In addition, overexpression of AKT rescued IEC apoptosis caused by MPST deficiency, while inhibition of AKT significantly aggravated it. CONCLUSIONS: MPST protects the intestines from inflammation most likely by regulating the AKT/apoptosis axis in IECs. Our results may provide a novel therapeutic strategy for the treatment of colitis.

Profiles of Acetylation Regulation Genes Contribute to Malignant Progression and Have a Clinical Prognostic Impact on Liver Cancer.

Background: Several studies have demonstrated that acetylation was involved in the process of liver cancer. This study aimed to establish an effective predictive prognostic model using acetylation regulation genes in liver cancer. Methods: Two datasets were downloaded from the Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database. Differentially expressed acetylation regulation genes were identified in the TCGA-LIHC dataset, and then, Gene Ontology (GO) functional annotation analysis was used to investigate the molecular mechanism. After grouping the patients into clusters based on consensus clustering, we explored the correlation between clusters and clinical characteristics. A risk model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis to calculate the risk score. Patients were divided into high-risk and low-risk groups according to the risk score using the acetylation regulation genes. Data downloaded from LIRI-JP were used for external validation. Univariate and multivariate Cox regressions were performed to identify independent risk factors. A prognostic nomogram was constructed according to the TCGA-LIHC dataset. The effect of HDAC11 expression on the proliferation and migration of liver cancer was detected by the CCK-8 method and cell scratch test, respectively. Results: Eleven of 29 acetylation regulation genes were identified as upregulated differentially expressed genes. Go enrichment analysis showed that they were involved in "protein and histone deacylation and deacetylation." Patients were categorized into two clusters according to the expression of 29 acetylation regulation genes. Compared with cluster 2, cluster 1 correlated with shorter overall survival (OS) and higher expression. Stage, T stage, grade, gender, age, and follow-up state were significantly different between two clusters. Pathways involved in DNA repair were significantly enriched in cluster 1. The risk score was calculated by HDAC1, HDAC2, HDAC4, HDAC11, HAT1, and SIRT6. Patients in the high-risk group had a worse prognosis in both datasets. Risk score was not only an independent prognostic marker but could also predict the clinicopathological features of liver cancer. A nomogram containing risk score, T stage, and M stage was built to predict overall survival. After transfection with HDAC11 overexpression plasmid, the proliferation ability of HepG2 cells increased, while the migration ability had no change. Conclusions: Our findings suggested that acetylation regulation genes contribute to malignant progression and have a clinical prognostic impact on liver cancer.

Exogenous proline enhances susceptibility of NSCLC to cisplatin via metabolic reprogramming and PLK1-mediated cell cycle arrest.

The occurrence of cisplatin resistance is still the main factor limiting the therapeutic effect of non-small cell lung cancer (NSCLC). It is urgent to elucidate the resistance mechanism and develop novel treatment strategies. Targeted metabolomics was first performed to detect amino acids' content in cisplatin-resistant cancer cells considering the relationship between tumour metabolic rearrangement and chemotherapy resistance and chemotherapy resistance. We discovered that levels of most amino acids were significantly downregulated, whereas exogenous supplementation of proline could enhance the sensitivity of NSCLC cells to cisplatin, evidenced by inhibited cell viability and tumour growth in vitro and xenograft models. In addition, the combined treatment of proline and cisplatin suppressed ATP production through disruption of the TCA cycle and oxidative phosphorylation. Furthermore, transcriptomic analysis identified the cell cycle as the top enriched pathway in co-therapy cells, accompanied by significant down-regulation of PLK1, a serine/threonine-protein kinase. Mechanistic studies revealed that PLK1 inhibitor (BI2536) and CDDP have synergistic inhibitory effects on NSCLC cells, and cells transfected with lentivirus expressing shPLK1 showed significantly increased toxicity to cisplatin. Inhibition of PLK1 inactivated AMPK, a primary regulator of cellular energy homeostasis, ultimately leading to cell cycle arrest via FOXO3A-FOXM1 axis mediated transcriptional inhibition in cisplatin-resistant cells. In conclusion, our study demonstrates that exogenous proline exerts an adjuvant therapeutic effect on cisplatin resistance, and PLK1 may be considered an attractive target for the clinical treatment of cisplatin resistance in NSCLC.

Transcription factor KLF16 activates MAGT1 to regulate the tumorigenesis and progression of breast cancer.

Breast cancer is the most frequent cause of cancer­related mortality among women worldwide. The present study aimed to explore the role of magnesium transporter protein 1 (MAGT1) in breast cancer and to illustrate the potential underlying molecular mechanisms. Bioinformatic analysis was performed to explore the association between MAGT1 expression and patients with breast cancer. MTT, colony formation, wound healing and Transwell assays were performed to examine the proliferative, migratory and invasive abilities of MCF­7 cells. Western blot analysis was conducted to determine the corresponding protein expression. Chromatin immunoprecipitation and luciferase reporter assays were carried out to reveal the interaction between MAGT1 and the Kruppel­like factor 16 (KLF16). In addition, an experimental animal model was established by the subcutaneous injection of MCF­7 cells into BALB/c nude mice, and tumor weight and size were measured. The results revealed that MAGT1 expression was upregulated in breast cancer. MAGT1 knockdown significantly suppressed the MCF­7 cell proliferative, migratory and invasive abilities, and downregulated the protein expression of Ki67, proliferating cell nuclear antigen, MMP2 and MMP9. MAGT1 knockdown also markedly suppressed tumor growth in vivo. Moreover, KLF6 could bind to the MAGT1 promoter and positively regulate MAGT1 expression. The inhibitory effects of KLF6 knockdown on cell proliferation, migration and invasion in vitro, and tumor growth in vivo were partly abolished by MAGT1 overexpression. On the whole, the findings of the present study suggest that MAGT1 knockdown exerts notable inhibitory effects on the progression of breast cancer, providing a potential therapeutic target for the treatment of breast cancer.

The DEAD-box helicase DDX3x ameliorates non-alcoholic fatty liver disease via mTORC1 signalling pathway.

BACKGROUND & AIMS: The DEAD (Asp-Glu-Ala-Asp)-box helicase family member DDX3x has been proven to involve in hepatic lipid disruption during HCV infection. However, the role of DDX3x in non-alcoholic fatty liver disease (NAFLD), in which lipid homeostasis is severely disrupted, remains unclear. Here, we aimed to illustrate the potential role of DDX3x in NAFLD. METHODS: DDX3x protein levels were evaluated in NAFLD patients and NAFLD models via immunohistochemistry or western blotting. In vivo ubiquitin assay was performed to identify the ubiquitination levels of DDX3x in the progression of steatosis. DDX3x protein levels in mice livers were manipulated by adeno-associated virus-containing DDX3x short hairpin RNA or DDX3x overexpression plasmid. Hepatic or serum triglyceride and total cholesterol were evaluated and hepatic steatosis was confirmed by haematoxylin and eosin staining and oil red o staining. Western blotting was performed to identify the underlying mechanisms of DDX3x involving in the progression of NAFLD. RESULTS: DDX3x protein levels were significantly decreased in NAFLD patients and NAFLD models. DDX3x protein might be degraded via ubiquitin-proteasome system in the progression of steatosis. Knockdown of hepatic DDX3x exacerbated HFD-induced hepatic steatosis in mice, while overexpression of hepatic DDX3x alleviated HFD-induced hepatic steatosis in mice. Further explorative experiments revealed that knockdown of DDX3x could lead to the overactivation of mTORC1 signalling pathway which exacerbates NAFLD. CONCLUSIONS: DDX3x involved in the progression of NAFLD via affecting the mTORC1 signalling pathway. DDX3x might be a potential target for NAFLD treatment.

Young Children Allergic Rhinitis Questionnaire is a novel tool for allergy screening in children.

BACKGROUND: There are a limited number of validated questionnaires available for use in the clinical screening for allergic rhinitis (AR) in children ≤3 years old. We developed a novel self-reported questionnaire and assessed its accuracy and reliability. METHODS: After establishing a pool of items, which were screened by experts, the Young Children Allergic Rhinitis Questionnaire (YCAR-Q) was administered to a birth cohort in the Shunyi District (Beijing, China). The electronic version of the YCAR-Q was distributed through the online community. Children were invited to visit a physician for examination. The diagnostic criteria included symptoms, physical examination findings, and specific serum immunoglobulin E tests. Each item on the questionnaire was evaluated, and the questionnaire's internal consistency, content validity, criterion-related validity, and diagnostic accuracy were assessed. RESULTS: The six-item YCAR-Q was distributed to 7423 parents, and 3037 valid questionnaires were recovered. In total, 1521 children visited a physician for examination, of which 82 were found to have AR. In terms of internal consistency, Cronbach's coefficient was 0.777 and all six questionnaire items were retained. The average scale-level content validity index value was 1. The area under the curve was 0.759. The total scores ranged from 0 to 6, and the cutoff value for diagnosing AR was 3, with a sensitivity of 68.29% and a specificity of 76.58%. CONCLUSIONS: This cross-sectional study indicated that the YCAR-Q could detect AR in children ≤3 years old. This brief and simple test may be used effectively in clinical practice.

Extracellular ATP and cAMP signaling promote Piezo2-dependent mechanical allodynia after trigeminal nerve compression injury.

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, a mechanically gated ion channel that mediates tactile allodynia in neuropathic pain, can be potentiated by a cyclic adenosine monophosphate (cAMP)-dependent signaling pathway that involves the exchange protein directly activated by cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization in a rat model of TN after trigeminal nerve compression injury, the expression of Piezo2 and activation of cAMP signal-related molecules in the trigeminal ganglion (TG) were detected. Changes in purinergic P2 receptors in the TG were also studied by RNA-seq. The expression of Piezo2, cAMP, and Epac1 in the TG of the TN animals increased after chronic compression of the trigeminal nerve root (CCT) for 21 days, but Piezo2 knockdown by shRNA in the TG attenuated orofacial mechanical allodynia. Purinergic P2 receptors P2X4, P2X7, P2Y1, and P2Y2 were significantly up-regulated after CCT injury. In vitro, Piezo2 expression in TG neurons was significantly increased by exogenous adenosine 5'-triphosphate (ATP) and Ca2+ ionophore ionomycin. ATP pre-treated TG neurons displayed elevated [Ca2+ ]i and faster increase in responding to blockage of Na+ /Ca2+ exchanger by KB-R7943. Furthermore, mechanical stimulation of cultured TG neurons led to sustained elevation in [Ca2+ ]i in ATP pre-treated TG neurons, which is much less in naïve TG neurons, or is significantly reduced by Piezo2 inhibitor GsMTx4. These results indicated a pivotal role of Piezo2 in peripheral mechanical allodynia in the rat CCT model. Extracellular ATP, Ca2+ influx, and the cAMP-to-Epac1 signaling pathway synergistically contribute to the pathogenesis and the persistence of mechanical allodynia.

Intestinal ulcers in a patient with myelodysplastic syndrome: a case report.

BACKGROUND: Trisomy 8 positivity myelodysplastic syndrome with Behçet's disease is rare. Isolated trisomy 8 is a frequent cytogenetic abnormality in the MDS, but the characteristic of trisomy 8 and the association between trisomy 8 positivity myelodysplastic syndrome and Behçet's disease is unclear. CASE PRESENTATION: Here, we reported a 63-year-old man, who presented with fever, abdominal pain and hematochezia. Imaging studies revealed bowel wall thickening and mural hyperenhancement of terminal ileum and cecum. Colonoscopy found multiple round ulcers in terminal ileum, ileocecal valve and multiple yellow dotted pseudomembranous attachments throughout the colon. Capsule endoscopy also revealed multiple irregular ulcers in lower ileum. Serum C-reactive protein levels and fecal calprotectin were abnormally high. The clostridium difficile toxin A and B was positive. However, the patient's intestinal ulcers did not resolve after two weeks course of vancomycin. Considered that the patient was diagnosed as MDS-RAEB2 with a karyotype of 47 XX, + 8. And detailed inquiry of medical history revealed epifolliculitis and frequently recurrent oral ulcers 2 months before admission. A diagnosis of trisomy 8 positivity MDS with BD was made. Then he received glucocorticoid along with the 5th course of azacytidine. The follow-up endoscopy showed significantly improved intestinal ulcer 2 months after treatment. we report a rare disease and provide the diagnose and treatment ideas. CONCLUSIONS: We highlight the challenges and the process of thinking about of the diagnosis. This may provide a new idea for the diagnosis of intestinal ulcers.