Clinical review and literature analysis of hepatic epithelioid angiomyolipoma in alcoholic cirrhosis: A case report.

BACKGROUND: Hepatic epithelioid angiomyolipoma (HEA) has a low incidence and both clinical manifestations and imaging lack specificity. Thus, it is easy to misdiagnose HEA as other tumors of the liver, especially in the presence of liver diseases such as hepatitis cirrhosis. This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis, and analyzed the literature, in order to improve the understanding of this disease. CASE SUMMARY: A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver. Based on the patient's history, laboratory examinations, and imaging examinations, a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed. Postoperative pathology showed HEA. During outpatient follow-up, the patient showed no sign of recurrence. CONCLUSION: HEA is difficult to make a definite diagnosis before surgery. HEA has the potential for malignant degeneration. If conditions permit, surgical treatment is recommended.

Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is the predominant type of thyroid cancer, with some patients experiencing relapse, distant metastases, or refractoriness, revealing limited treatment options. Chimeric antigen receptor (CAR)-modified Natural Killer (NK) cells are revolutionary therapeutic agents effective against various resistant cancers. Thyroid-stimulating hormone receptor (TSHR) expression in DTC provides a unique tumor-specific target for CAR therapy. Here, we developed an innovative strategy for treating DTC using modified NK-92 cells armed with a TSHR-targeted CAR. The modified cells showed enhanced cytotoxicity against TSHR-positive DTC cell lines and exhibited elevated degranulation and cytokine release. After undergoing irradiation, the cells effectively halted their proliferative capacity while maintaining potent targeted killing ability. Transfer of these irradiation-treated cells into NSG mice with DTC tumors resulted in profound tumor suppression. NK-92 cells modified with TSHR-CAR offer a promising, off-the-shelf option for advancing DTC immunotherapy.

A Novel Laryngopharyngeal Reflux Disease Model for Bama Pigs.

OBJECTIVE: To develop a novel Laryngopharyngeal Reflux Disease (LPRD) model in Bama pigs through endoscopic cricopharyngeal myotomy. METHODS: A total of eight 8-month-old Bama pigs were randomly assigned to either the control or surgery group. Prior to intervention, upper esophageal sphincter (UES) manometry and laryngopharyngeal Dx-pH monitoring were conducted to establish baseline physiological parameters for each pig. Subsequently, the surgery group underwent endoscopic cricopharyngeal myotomy, while the control group did not. Two weeks postintervention, these procedures were repeated to evaluate changes in UES contractility and the occurrence of reflux events. At week eight postsurgery, mucosal tissues from both groups were harvested for histological analysis. Hematoxylin and eosin (H&E) staining was used to assess inflammation, while transmission electron microscopy (TEM) examined alterations in intercellular spaces and desmosomes. RESULTS: The mean UES pressures in the control and surgery groups were 59 ± 9 mmHg and 68 ± 12 mmHg, respectively. In the surgery group, there was a significant decrease in UES pressure 2weeks after the operation compared to preoperative values (P = 0.005), whereas no significant change was observed in the control group (P = 0.488). Laryngopharyngeal reflux (LPR) was successfully induced in the surgery group as evidenced by reflux events with pH <5.0, which were not detected in the control group. HE staining revealed marked inflammatory cell infiltration and submucosal gland expansion in throat tissues of the surgery group Bama pigs. TEM further showed enlarged intercellular spaces and reduced desmosome numbers in the laryngopharyngeal epithelium compared to controls. CONCLUSION: Given analogous throat epithelial structures to humans, Bama pigs are an appropriate species for an LPRD animal model. Endoscopic cricopharyngeal myotomy effectively induces LPR and observable pathological changes in Bama pigs, providing a valuable platform for further research into LPRD pathophysiology.

Pathological features of gastric­type endocervical adenocarcinoma: A report of two cases.

Gastric-type endocervical adenocarcinoma (GEA) is an uncommon form of uterine cervical adenocarcinoma with an unfavorable prognosis. The tumor consists of glands exhibiting a morphological resemblance to gastric cells and occasionally manifests features akin to pancreaticobiliary mucinous adenocarcinoma. GEA differs from the typical cervical cancer, particularly in its lack of association with the human papillomavirus. Immunophenotypic analysis suggests intestinal differentiation. The present study reports two cases of GEA occurring in postmenopausal individuals who were diagnosed in Lishui Central Hospital (Lishui, China) between January 2015 and January 2023. Microscopic examination revealed cysts lined with mucinous cells within the tumors. Immunohistochemical assays confirmed the positivity of the tumors for cytokeratin 7, mucin (MUC)5AC, and mutant tumor protein p53, while the results were negative for tumor suppressor p16, and in one case for paired box protein 8, consistent with characteristics of mucinous adenocarcinoma originating from the gastrointestinal tract. Programmed death-ligand 1 expression was also negative. The proto-oncogene K-ras was identified using amplification refractory mutation system polymerase chain reaction. Both cases were negative for mutations in codons 12 and 13 of exon 2, codon 61 of exon 3 and codon 146 of exon 4, but were positive for wild-type K-ras. Clinical follow-up revealed a potential association between histopathological features and resistance to chemotherapeutic drugs. The infrequency of this tumor type may contribute to diagnostic challenges.

The effectiveness of E-health interventions promoting physical activity in cancer survivors: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to identify whether E-health interventions effectively improve physical activity (PA) in cancer survivors. METHODS: PubMed, Web of Science, and Cochrane Library databases were searched from inception to October 21, 2023. Randomized controlled trials reporting the effect of E-health interventions on PA among cancer survivors were included. Random-effect models were used to calculate standardized mean differences (SMD) and the 95% confidence interval (CI). RESULTS: In total, 15 trials with 2,291 cancer survivors were included in this meta-analysis. The results showed that E-health interventions improved moderate to vigorous physical activity (MVPA) among cancer survivors (SMD = 0.26, 95% CI 0.08, 0.43, N = 8, p < 0.001, I2 = 37%), as well as moderate physical activity (MPA) (SMD = 0.22, 95% CI 0.05, 0.38, N = 9, p < 0.001, I2 = 28%) and vigorous physical activity (VPA) (SMD = 0.34, 95% CI 0.15, 0.54, N = 6, p < 0.001, I2 = 11%). CONCLUSION: E-health interventions are effective at promoting PA among cancer survivors. As current research primarily focuses on immediate post-intervention measurements with limited follow-up data, further investigation is required to explore the long-term effects of E-health interventions on PA.

Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study.

AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.

In clinics, hepcidin levels are elevated in various anemia-related conditions, particularly in iron-refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron-refractory anemia, the potential effect of hypoxia and pharmacologically-mimetic drug FG-4592 (Roxadustat) are evaluated, a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor, on mouse models of iron-refractory iron-deficiency anemia (IRIDA), anemia of inflammation and 5-fluorouracil-induced chemotherapy-related anemia. The potent protective effects of both hypoxia and FG-4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG-4592 could stabilize duodenal Hif2α, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin-activated anemias. Moreover, duodenal Hif2α overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2α knockout in the gut significantly delays the recovery from 5-fluorouracil-induced anemia, which can not be rescued by FG-4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia-related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia.

The percentage of controlled chronic rhinosinusitis after treatment: a systematic review and meta-analysis.

PURPOSE: Chronic rhinosinusitis (CRS) is a chronic disease with a high recurrence rate, and the aim of treating CRS is to maintain disease control. Recently, a series of CRS control instruments have been developed to assess the control levels. We pooled existing studies to evaluate the percentage of controlled CRS after treatment in patients with CRS. METHODS: A systematic literature review and meta-analysis using PubMed, Google Scholar, Scopus, and Cochrane databases was conducted to identify studies assessing CRS control. Both comprehensive assessments and self-report of CRS control were included. RESULTS: 9 studies with 1931 patients after treatment and 295 patients before treatment were included. CRS control assessments of the 2012 European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2012), EPOS 2020, and Sinus Control Test (SCT) were comprehensive assessments utilized in the clinic practice. The self-report assessment included patient-reported global level of CRS control. These existing disease control instruments categorized patients into three (uncontrolled, partly controlled, and controlled) or five (not at all, a little, somewhat, very, and completely) control categories. Only 8% (95% CI 0.05-0.11) of patients with CRS stayed well controlled before treatment assessed by comprehensive assessments. About 35% (95% CI 0.22-0.49) of patients achieved well controlled after treatment when assessed by the comprehensive measures. Meanwhile, 40% (95% CI 0.28-0.52) of patients reported well controlled after treatment when using self-report. CONCLUSION: About 35-40% of patients with CRS showed well controlled after treatment, which stressed the importance of identifying these undertreated patients with CRS.

Investigation of manganese-iron oxide nanocomposite immobilized on powdered activated carbon as an efficient activator of peroxymonosulfate for antibiotics degradation: Conjunction of adsorption, radical and nonradical processes.

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) have gained considerable attention for their efficient oxidation of persistent pollutants. A two-step chemical co-precipitation method was used to prepare a bimetallic nanocomposite (MnOx@Fe3O4) consisting of manganese oxides and ferroferric oxides, supported by powdered activated carbon (PAC). The synthesis of MnOx@Fe3O4-PAC (MFP) was aimed to enhance the degradation efficiency of oxytetracycline (OTC) via the simultaneous adsorption and oxidation processes on the solid-liquid interface. The OTC degradation process in the MFP/PMS system could be well described by pseudo-first-order kinetics. A wide pH range (3-6) was acceptable for MFP to degrade OTC via PMS activation with the highest removal efficiency reaching up to 85.6% (OTC0 = 150 mg/L), while a 60.8% removal efficiency of total organic carbon (TOC) was also attained simultaneously. SO4•- and 1O2, which were bound to the surface, played a crucial role as reactive oxygen species in the degradation of OTC. The combination of PAC, Fe3O4, and MnOx of MFP could enhance the degradation efficiency of OTC and fetch up their defects of separate application. The deduced OTC degradation pathway relied on the findings from UPLC-MS analysis and density functional theory (DFT) calculations. Noteworthy, MFP maintained efficient catalysis performance in the five cycles of stability experiment with neglectable loss of manganese and iron. These results provide valuable understanding of the conjunction of adsorption, radical, and nonradical processes driven by MFP for OTC degradation.

Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients.

BACKGROUND: Tenofovir alafenamide (TAF) has a serum lipid-raising effect in patients with HIV; however, its effect on serum lipids and nonalcoholic fatty liver disease (NAFLD) risk in patients with chronic hepatitis B (CHB) is unclear. AIM: To compare the effects of TAF and entecavir (ETV) on serum lipid levels in patients with CHB. METHODS: In this retrospective cohort study, the data including the clinical features, serum lipids, and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed. We used propensity score-matched models to assess the effects on high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol (TCHO). RESULTS: A total of 336 patients (75.60% male) were included; 63.69% received TAF and 36.31% received ETV. Compared with the ETV group, the TAF group had significantly higher TCHO levels after treatment (4.67 ± 0.90 vs 4.36 ± 1.05, P = 0.006). In a propensity score-matched model for body mass index, age, sex, smoking, drinking, presence of comorbidities such as NAFLD, cirrhosis, diabetes mellitus, and hypertension, TAF-treated patients had significantly increased TCHO levels compared to that at baseline (P = 0.019). There was no difference for the ETV group. Body mass index, sex, hypertension, baseline TCHO, and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis. However, 1-year TAF treatment did not increase the incidence of NAFLD. CONCLUSION: A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV. However, TAF-induced dyslipidemia did not increase the incidence of NAFLD.

CT and PET/CT findings of primary pulmonary malignant melanoma: a case report and literature review.

Primary malignant melanoma of the lung (PMML) is an extremely rare and refractory tumor, and its diagnosis is a significant challenge. The current study presents the case of a 62-year-old man who presented to the Department of Cardiothoracic Surgery (Lishui Municipal Central Hospital, Lishui, China) with chest tightness and fatigue for 3 months. Chest computed tomography (CT) revealed a 1.5- × 1.9-cm mass with irregular borders and heterogenous density located in the right lower lung lobe. Contrast-enhanced CT revealed slight enhancement of the mass, but there was no clear evidence of malignancy. Positron emission tomography (PET)/CT revealed a defined-margin mass, with slightly high uptake (standardized uptake value [SUV]: 3.6). The patient underwent video-assisted thoracoscopic surgery (VATS), and the final diagnosis was PMML on the basis of the results of the pathological examination. The patient received four courses of immunotherapy after the operation, and eventually declined further immunotherapy owing to the high cost. The patient was followed-up for 1 year without metastasis or recurrence.

The crosstalk between anoikis and epithelial-mesenchymal transition and their synergistic roles in predicting prognosis in colon adenocarcinoma.

Anoikis and epithelial-mesenchymal transition (EMT) are significant phenomena occurring in distant metastasis of colon adenocarcinoma (COAD). A comprehensive understanding of their crosstalk and the identification of key genes are vital for treating the distant metastasis of COAD. The objective of this study was to design and validate accurate prognostic predictors for COAD patients based on the anoikis and EMT processes. We obtained gene signatures from various databases and performed univariate and multivariate Cox regression analyses, principal component analysis (PCA). The COAD patients were categorized into the worst prognosis group, the Anoikis Potential Index (API) Low + EMT Potential Index (EPI) High group and the others group. Then we utilized gene set enrichment analysis (GSEA) to identify differentially expressed genes and to establish a prognostic risk model. The model classified patients into high- or low-risk groups, with patients in the high-risk group displaying worse survival status. A nomogram was established to predict overall survival rates, demonstrating high specificity and sensitivity. Additionally, we connected the risk model to the tumor microenvironment (TME) using single-sample GSEA and the MCP counter tool, as well as evaluated the sensitivity to common chemotherapeutic drugs, such as Gefitinib and Gemcitabine. Lastly, cell and tissue experiments suggested a positive correlation among anoikis resistance, EMT, and liver/lung metastasis of COAD. This is the first study to comprehensively analyze the crosstalk between anoikis and EMT and offers new therapeutic targets for COAD metastasis patients.

Current understanding of disease control and its application in patients with chronic rhinosinusitis.

Background: Disease control is a primary treatment goal for patients with chronic rhinosinusitis (CRS). This study aims to summarize the evaluation parameters of disease control and then identify predictors of poorly controlled CRS. Methods: A systematic review of the literature was performed on PubMed, Google Scholar, Scopus, and Cochrane databases to identify studies relating to disease control in CRS. Results: The concept of disease control in patients with CRS involved the longitudinal assessment of the disease state and was also an important goal of treatment. As a metric of the disease state, the disease control reflected the ability to keep disease manifestations within certain limits, the efficacy after treatment, and the impact on quality of life. Validated measurements, such as EPOS2012 criteria, EPOS2020 criteria, Sinus Control Test, and patient/physician-reported global level of CRS control, have been utilized in clinical practice. These existing disease control instruments incorporated various disease manifestations and categorized patients into two (well-controlled and poor-controlled), three (uncontrolled, partly controlled, and controlled), or five (not at all, a little, somewhat, very, and completely) control categories. Eosinophilia, high computerized tomography score, bilateral sinonasal disease, asthma, allergic rhinitis, female gender, aspirin intolerance, revision surgery, low serum amyloid A, and specific T cell subtype would predict poorly controlled CRS. Conclusion: The concept of disease control and its application were gradually developed in patients with CRS. The existing disease control instruments demonstrated a lack of uniformity regarding the controlled criteria and included parameters.

Discourse-based psychological intervention alleviates perioperative anxiety in patients with adolescent idiopathic scoliosis in China: a retrospective propensity score matching analysis.

PURPOSE: To evaluate the effectiveness of a discourse-based psychological intervention on perioperative anxiety, pain and life satisfaction of patients with AIS. METHODS: Between April 2018 and February 2021, 116 consecutive patients with AIS undergoing corrective surgery were enrolled in this study, including 51 with personalized psychological intervention (intervention group, IG) and 65 without (control group, CG). After propensity score matching (PSM), patient characteristics, perioperative scores of anxiety and life satisfaction, measured by values of Generalized Anxiety Disorder 7-item Scale (GAD-7) and Life Satisfaction Index Z scale (LSIZ), were recorded. Mixed linear models were used to estimate the influence of intervention group and time of measurement, as well as their interactions, in anxiety and life satisfaction. Data on post-surgical pain in both groups was also collected and analyzed. RESULTS: After PSM, a total of 90 patients (IG, n = 45; CG, n = 45) were enrolled in this study, and the 2 groups were comparable in patients' demographic and baseline characteristics. There were no pre-intervention between-group differences in the degree of anxiety (IG: 3.98 ± 3.27 vs. CG: 3.93 ± 3.20, p = .948, Cohen's d = 0.015), and life satisfaction (IG: 6.56 ± 1.70 vs. CG: 6.67 ± 2.09, p = .783, Cohen's d = -0.058). After surgery, participants in both IG and CG showed improved the levels of anxiety (GAD-7: IG 2.18 ± 1.21; CG 2.87 ± 2.00) and life satisfaction (LSIZ: IG 9.84 ± 2.09; CG 9.02 ± 2.15). A stratified analysis of patients with generalized anxiety disorder showed improved anxiety (GAD-7: IG 3.50 ± 1.22 vs. CG 6.80 ± 2.05, p = .017, Cohen's d = -1.956) and lower pain level (VAS: IG 4.50 ± 1.76 vs. CG 7.00 ± 1.00, p = .017, Cohen's d = -1.747) in the IG than the CG after surgery. CONCLUSIONS: Discourse-based psychological intervention before surgery can improve perioperative anxiety and life satisfaction, and postoperative painful condition, especially for patients with high-leveled pre-surgical anxiety.

A novel UPLC-ESI-MS assay for fifteen portal estrogens and metabolites detection and application in hepatic fibrosis.

Estrogens and their metabolites (EMs) are involved in chronic liver disease and gut microbiota regulates estrogen metabolism, whereas the role of enterogenous EMs in liver disease is still elusive. Because of the extremely low level of EMs in portal serum and the EMs contain multiple pairs of isomers, an accurate determination of portal serum EMs is urgently needed. This study established a quantitative detection method for portal serum EMs and applied to non-alcoholic fatty liver disease (NAFLD) related hepatic fibrosis mice model. The serum was derived with a novel derivatization reagent 4-acetyl aminobenzene sulfonyl chloride, and a UPLC-ESI-MS system was used for quantification of 15 EMs in 120 min. Compared with normal group, the concentrations of E1, E2 in model group were significantly decreased by 4-8 times, all the C2 and C4 substitution products (2-OHE1, 2-OHE2, 2-MeOE1, 4-OHE1, 4-MeOE1, 4-OHE2, 4-MeOE2, 2-MeOE2) were significantly decreased by 2-22 times. However, the C16 and C17 substitution products (E3, 16-epiE3, 17-epiE3, 16-ketoE2) levels were increased by 3-5 times (P < 0.01). This study elucidated the changes of enterogenous EMs which entered the liver via portal vein in NAFLD - related hepatic fibrosis and provided methodological platform for other related studies on estrogen metabolism.

A generalizable strategy for crosslinkable albumin-based hydrogels and application as potential anti-tumor nanoplatform.

Albumin-based hydrogels have emerged as promising nanoparticle systems for the effective delivery of hydrophobic anticancer drugs. Anti-cancer drugs often cause some adverse effects, such as toxicity and rapid clearance by mononuclear phagocytic systems. Herein, a new strategy of synthesizing N-hydroxysuccinimide (NHS)-activated linker to form crosslinkable albumin-based hydrogels (CABH) is reported. The CABH favored physiochemical characteristics improvement of doxorubicin (Dox) and drug release. The CABH was constructed depending on the crosslinking reaction between NHS activated glycerol and albumin. The size of CABH was approximately 200 nm examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that the particle size and size distribution of the CABH remained stable in neutral PBS for 1 week. Dox loaded CABH would be controllably released in weak acidic environment verified by in vitro release and in vitro cell imaging. The Dox loaded hydrogel results in significant killing in the case of acidic culture medium. Our work provides a crosslinking method to formulate albumin nanoplatform and improve the size, stability, drug loading capacity and controlled release, which throws light on the potential application in drug delivery.

IL1RAP Knockdown in LPS-Stimulated Normal Human Astrocytes Suppresses LPS-Induced Reactive Astrogliosis and Promotes Neuronal Cell Proliferation.

The reactivation of astrocytes plays a critical role in spinal cord injury (SCI) repairment. In this study, IL1RAP expression has been found to be upregulated in SCI mice spinal cord, SCI astrocytes, and LPS-stimulated NHAs. Genes correlated with IL1RAP were significantly enriched in cell proliferation relative pathways. In LPS-stimulated NHAs, IL1RAP overexpression promoted NHA cell proliferation, decreased PTEN protein levels, and increased the phosphorylation of Akt and mTOR. IL1RAP overexpression promoted LPS-induced NHA activation and NF-κB signaling activation. Conditioned medium from IL1RAP-overexpressing NHAs inhibited SH-SY5Y cells viability but promoted cell apoptosis. Conclusively, IL1RAP knockdown in LPS-stimulated NHAs could partially suppress LPS-induced reactive astrogliosis, therefore promoting neuronal cell proliferation.

Acetyltransferase NAT10 regulates the Wnt/ß-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA.

BACKGROUND: N4-acetylcytidine (ac4C) as a significant RNA modification has been reported to maintain the stability of mRNA and to regulate the translation process. However, the roles of both ac4C and its 'writer' protein N-acetyltransferase 10 (NAT10) played in the disease especially colorectal cancer (CRC) are unclear. At this point, we discover the underlying mechanism of NAT10 modulating the progression of CRC via mRNA ac4C modification. METHODS: The clinical significance of NAT10 was explored based on the TCGA and GEO data sets and the 80 CRC patients cohort of our hospital. qRT-PCR, dot blot, WB, and IHC were performed to detect the level of NAT10 and ac4C modification in CRC tissues and matched adjacent tissues. CCK-8, colony formation, transwell assay, mouse xenograft, and other in vivo and in vitro experiments were conducted to probe the biological functions of NAT10. The potential mechanisms of NAT10 in CRC were clarified by RNA-seq, RIP-seq, acRIP-seq, luciferase reporter assays, etc. RESULTS: The levels of NAT10 and ac4C modification were significantly upregulated. Also, the high expression of NAT10 had important clinical values like poor prognosis, lymph node metastasis, distant metastasis, etc. Furthermore, the in vitro experiments showed that NAT10 could inhibit apoptosis and enhance the proliferation, migration, and invasion of CRC cells and also arrest them in the G2/M phase. The in vivo experiments discovered that NAT10 could promote tumor growth and liver/lung metastasis. In terms of mechanism, NAT10 could mediate the stability of KIF23 mRNA by binding to its mRNA 3'UTR region and up-regulating its mRNA ac4c modification. And then the protein level of KIF23 was elevated to activate the Wnt/ß-catenin pathway and more ß-catenin was transported into the nucleus which led to the CRC progression. Besides, the inhibitor of NAT10, remodelin, was applied in vitro and vivo which showed an inhibitory effect on the CRC cells. CONCLUSIONS: NAT10 promotes the CRC progression through the NAT10/KIF23/GSK-3ß/ß-catenin axis and its expression is mediated by GSK-3ß which forms a feedback loop. Our findings provide a potential prognosis or therapeutic target for CRC and remodelin deserves more attention.

Overexpression of estrogen receptor ß inhibits cellular functions of human hepatic stellate cells and promotes the anti-fibrosis effect of calycosin via inhibiting STAT3 phosphorylation.

BACKGROUND: Estrogen receptor ß (ERß) is the major ER subtype in hepatic stellate cells (HSCs). Previously we reported phytoestrogen calycosin suppressed liver fibrosis progression and inhibited HSC-T6 cell functions, suggesting the effects may be related to ERß. Here, we explore the effect of overexpressed ERß on human HSCs and the role of ERß in pharmacological action of calycosin. METHODS: LX-2 cells were transfected with lentivirus to overexpress ERß. In the presence or absence of overexpressed ERß, the effects of ERß and calycosin on proliferation, migration, activation, collagen production and degradation of TGF-ß1-induced LX-2 cells and the role of ERß in the inhibition effect of calycosin were investigated. LX-2 cells overexpressed with ERß or treated with ER non-selective antagonist ICI182,780 were used to investigate the regulation of ERß on JAK2/STAT3 signaling pathway. CCK-8 method was used to screen effective doses of calycosin and investigate cell proliferation. The cell migration was detected by transwell chamber assay. The expression of α-SMA was detected by immunofluorescence and western blot. The protein expressions of Col-I, MMP1, TIMP1, JAK2, p-JAK2, STAT3 and p-STAT3 were detected by western blot. RESULTS: ERß overexpressed lentivirus was successfully transfected into LX-2 cells with high efficiency. Overexpressed ERß or calycosin alone inhibited the TGF-ß1-induced LX-2 cell proliferation and migration, downregulated the protein expressions of α-SMA, Col-I, TIMP-1, p-STAT3 and upregulated MMP-1. Both overexpressed ERß and calycosin had no significant effect on JAK2, p-JAK2 and STAT3 expressions. ERß overexpression further enhanced the above effects of calycosin. However, after the cells were treated with ICI182,780, downregulation of STAT3 phosphorylation induced by calycosin was reversed. CONCLUSIONS: ERß mediated the inhibition of major functions of LX-2 cell possibly by inhibiting the phosphorylation of STAT3, and was an important pathway through which calycosin exerted anti-liver fibrosis effect.

Effect of color protection treatment on the browning and enzyme activity of Lentinus edodes during processing.

Fresh Lentinus edodes (L. edodes) are prone to browning (including enzymatic and nonenzymatic browning), which affects their quality and leads to economic losses during later processing. This study explored various effective color protection methods (color protection reagent and/or blanching) for inhibiting the browning of L. edodes. First, a single-factor experiment and a response surface method were used to optimize the concentration of the color retention reagent. The compound color retention reagent (comprising 0.1% phytic acid, 0.8% sodium citrate, and 0.5% d-sodium erythorbate) had the smallest total color difference (ΔE) value, suggesting that the compound color reagent had a better inhibiting effect than the single agent. Following this, the blanching conditions were studied; the polyphenol oxidase (PPO) activity was the lowest when the blanching temperature was 90°C and blanching time 180 s, indicating that browning is likely to be minimal. Finally, comparing the oxidase activity and total color difference (ΔE) revealed that combining the two color protection methods inhibits browning better than using a single method (color protection reagent or blanching). In addition, the polysaccharide and vitamin C (VC) contents of L. edodes under optimal color protection conditions were determined, which were 0.96 and 2.54 g/100 g fresh weight (FW), respectively. The results demonstrated that this color protection method effectively inhibits browning, reduces the nutritional loss, and improves the quality of L. edodes.