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Propose: Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration-effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work. Methods: OBB-HP-ß-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-ß-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-ß-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers. Results: The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-ß-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-ß-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-ß-CD SDDS (10.882 µg/mL*h) was significantly higher than that of the raw OBB counterpart (0.701 µg/mL*h). The oral relative bioavailability of OBB-HP-ß-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-ß-CD SDDS was approximately 5-10 times higher than that of OBB raw material. Conclusion: Based on our findings above, OBB-HP-ß-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB.
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Berberina , Animales , Berberina/farmacocinética , Berberina/química , Berberina/administración & dosificación , Berberina/farmacología , Masculino , 2-Hidroxipropil-beta-Ciclodextrina/química , 2-Hidroxipropil-beta-Ciclodextrina/farmacocinética , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/sangre , Sistemas de Liberación de Medicamentos/métodos , Solubilidad , Nanopartículas/química , Ratas , Ratas Sprague-Dawley , Liberación de Fármacos , Tamaño de la Partícula , Disponibilidad Biológica , Ácido Úrico/química , Ácido Úrico/sangreRESUMEN
Porcine reproductive and respiratory syndrome (PRRS) is one of the most widespread illnesses in the world's swine business. To detect the antibodies against PRRSV-2, a blocking enzyme-linked immunosorbent assay (B-ELISA) was developed, utilizing a PRRSV-2 N protein monoclonal antibody as the detection antibody. A checkerboard titration test was used to determine the optimal detection antibody dilution, tested pig serum dilution and purified PRRSV coated antigen concentration. After analyzing 174 negative pig sera and 451 positive pig sera, a cutoff value of 40â¯% was selected to distinguish between positive and negative sera using receiver operating characteristic curve analysis. The specificity and sensitivity of the assay were evaluated to equal 99.8â¯% and 96â¯%, respectively. The method had no cross-reaction with PCV2, PRV, PPV, CSFV, PEDV, TGEV, and PRRSV-1 serum antibodies, and the coefficients of variation of intra-batch and inter-batch repeatability experiments were both <10â¯%. A total of 215 clinical serum samples were tested, and the relative coincidence rate with commercial ELISA kit was 99.06â¯%, and the kappa value was 0.989, indicating that these two detection results exhibited high consistency. Overall, the B-ELISA should serve as an ideal method for large-scale serological investigation of PRRSV-2 antibodies in domestic pigs.
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Anticuerpos Monoclonales , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Animales , Virus del Síndrome Respiratorio y Reproductivo Porcino/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Porcinos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Monoclonales/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/diagnóstico , Síndrome Respiratorio y de la Reproducción Porcina/sangre , Sensibilidad y Especificidad , Reproducibilidad de los Resultados , Proteínas de la Nucleocápside/inmunología , Curva ROCRESUMEN
RATIONALE: Most of the mature teratomas are found in the ovaries. Extragonadal teratomas are extremely rare. To date, there are only a handful of reports of uterine cervical teratomas documented in the English literature. PATIENT CONCERNS: Herein we describe a rare case of a 40-year-old patient who was presented to our hospital for a cervical polypoid mass, which was finally confirmed to be mature solid teratoma in uterine cervix. DIAGNOSES: Histological examination of the polypoid mass was found to consist of ciliated pseudostratified columnar respiratory epithelium, intestinal epithelium and smooth muscle tissue, adipose tissue and mature glial component, epidermis, and skin adnexa. Meanwhile, no history of abortion, dilatation, and curettage was present in this patient, so implantation of fetal tissue was excluded. Therefore, we make a diagnosis of uterine cervical mature teratoma. INTERVENTIONS: Tumorectomy was performed after discovering the cervical polypoid mass. OUTCOMES: The patient had been followed-up for next 3 months after surgery and no recurrence was documented until now. LESSONS: Though teratomas of the uterine cervix are extremely rare, more attention should be paid on this rare but possible tumor for appropriate treatment in these patients.
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Quiste Dermoide , Teratoma , Neoplasias del Cuello Uterino , Femenino , Embarazo , Humanos , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Teratoma/diagnóstico , Teratoma/cirugía , Teratoma/patología , Cuello del Útero/cirugía , Cuello del Útero/patología , Quiste Dermoide/patología , Útero/patologíaRESUMEN
OBJECTIVES: To investigate the correlations between physical activity (PA) and metabolic associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) within a substantial population-based survey, and to examine the association between PA and liver fibrosis (LF). METHODS: Data from the 2017-2020 NHANES cycle were utilized in this study. PA was divided into four types: leisure-time PA (LTPA), transportation-related PA (TPA), occupational PA (OPA) and total time PA (total PA, which is composed of OPA, TPA and LTPA). Weighted logistic regression models were performed to analyze the associations between PA and MAFLD/MASLD and LF. Mediation analysis was used to explore whether LTPA completely mediated the statistically significant relationship between total PA and MAFLD/MASLD or LF. RESULTS: The study encompassed a sample size of 5897 participants aged 20 years and above, among the total participants, 2568 individuals with MAFLD and 2588 individuals with MASLD. There was no statistically significant correlation observed between OPA/TPA and MAFLD/MASLD and LF; however, active LTPA demonstrated an inverse association with MAFLD/MASLD (OR: 0.548; 95% CI: 0.458, 0.656/OR: 0.543; 95% CI: 0.453, 0.650), as well as a negative correlation with significant/advanced LF (OR: 0.457; 95% CI: 0.334,0.625/OR: 0.427; 95% CI: 0.295,0.619). There was also a significant inverse association between total PA and MAFLD/MASLD or LF, but this association was carried by the difference in LTPA. CONCLUSION: Participation in active LTPA is associated with a reduced likelihood of MAFLD/MASLD and LF, while neither OPA nor TPA can replace these effects of LTPA.
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Ejercicio Físico , Hígado Graso , Enfermedad del Hígado Graso no Alcohólico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Hígado Graso/epidemiología , Actividades Recreativas , Cirrosis Hepática/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Encuestas Nutricionales , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
RATIONALE: As the third most common cancer in women, cervical cancer usually spreads to adjacent organs. Distant metastasis from the cervix to the gastrointestinal tract is an extremely rare occurrence. PATIENT CONCERNS: Herein, we present a rare case of a 57-year-old woman who was treated by hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy for squamous cell carcinoma (SCC) of the uterine cervix. A metastatic location in the sigmoid colon was revealed after 8 years causing an acute intestinal obstruction in this patient. DIAGNOSES: Final surgical pathology showed an invasive lesion with squamous differentiation in full thickness of the colon wall from mucosa to serosa. Meanwhile, the results of immunohistochemistry (IHC) showed the cancer cells were positive for CK5/6, P63, P40, and P16 confirming the diagnosis of metastatic sigmoid colonic carcinoma originating from SCC of the uterine cervix. INTERVENTIONS: Sigmoid colon resection with lymph node dissection followed by adjuvant chemotherapy (paclitaxel, carboplatin, and paprillizumab) was performed on the patient. OUTCOMES: The patient was disease-free 16 months after surgery. LESSONS SUBSECTIONS: SCC is one of the rare malignant tumors of the gastrointestinal tract occurring as either a primary or secondary lesion. However, the secondary SCC of the colon has a poorer prognosis compared with the primary SCC. Therefore, colonic metastasis must be considered in the differential diagnosis of acute intestinal obstruction, especially in patients with the medical history of SCC in other organs.
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Carcinoma de Células Escamosas , Obstrucción Intestinal , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Colon Sigmoide/cirugía , Colon Sigmoide/patología , Carcinoma de Células Escamosas/patología , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugíaRESUMEN
BACKGROUND: Colon cancer is a common malignant tumor in the gastrointestinal tract that is typically treated surgically. However, postradical surgery is prone to complications such as anastomotic fistulas. AIM: To investigate the risk factors for postoperative anastomotic fistulas and their impact on the prognosis of patients with colon cancer. METHODS: We conducted a retrospective analysis of 488 patients with colon cancer who underwent radical surgery. This study was performed between April 2016 and April 2019 at a tertiary hospital in Wuxi, Jiangsu Province, China. A t-test was used to compare laboratory indicators between patients with and those without postoperative anastomotic fistulas. Multiple logistic regression analysis was performed to identify independent risk factors for postoperative anastomotic fistulas. The Functional Assessment of Cancer Therapy-Colorectal Cancer was also used to assess postoperative recovery. RESULTS: Binary logistic regression analysis revealed that age [odds ratio (OR) = 1.043, P = 0.015], tumor, node, metastasis stage (OR = 2.337, P = 0.041), and surgical procedure were independent risk factors for postoperative anastomotic fistulas. Multiple linear regression analysis showed that the development of postoperative anastomotic fistula (P = 0.000), advanced age (P = 0.003), and the presence of diabetes mellitus (P = 0.015), among other factors, independently affected prognosis. CONCLUSION: Postoperative anastomotic fistulas significantly affect prognosis and survival rates. Therefore, focusing on the clinical characteristics and risk factors and immediately implementing individualized preventive measures are important to minimize their occurrence.
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RATIONALE: The majority of rectal malignancies are primary tumors, secondary tumors are unusual. The rectal metastasis of endometrial carcinoma is reported to be extremely rare, especially in the absence of endometriosis. PATIENT CONCERNS: Herein we present a rare case of a 68-year-old postmenopausal woman with a history of endometrial adenocarcinoma, metastasizing to the rectum 5 years after a hysterectomy and bilateral salpingo-oophorectomy treatments with pelvic lymphadenectomy were performed. DIAGNOSES: Histological examination of the rectal neoplasm revealed an invasive lesion in submucosal and muscular layers without definitely invaded evidence in the serous membrane and there was also no obvious endometriosis. The results of immunohistochemistry showed the cancer cells were positive for CK7, estrogen receptor, progesterone receptor, and negative for CK20, villin, confirming the diagnosis of metastatic rectal adenocarcinoma originating from uterine endometrial adenocarcinoma. Meanwhile, the results of immunohistochemical staining showed positive expression of MSH2, MSH6, and negative expression of MLH1 and PMS2, hinting at microsatellite instability which may be related to Lynch syndrome. INTERVENTIONS: The Dixon operation with lymph node dissection was performed. Chemotherapy was also performed on this patient for the next 6 months. OUTCOMES: The patient was followed up for the next 6 months after surgery and no recurrence was documented until now. LESSONS SUBSECTIONS: Though rectal and endometrial adenocarcinoma could share some similar morphologic features, different immunohistochemical profiles could be revealed between them. Most endometrial carcinoma in the colon or rectum develop from endometriosis. Secondary rectal cancer with endometrial origination in the absence of endometriosis and serosal implants was extremely rare. Therefore, we should pay more attention to this rare but possible presentation for appropriate diagnosis and treatment of these patients.
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Adenocarcinoma , Neoplasias Endometriales , Endometriosis , Neoplasias del Recto , Femenino , Humanos , Anciano , Endometriosis/patología , Neoplasias Endometriales/patología , Endometrio/patología , Adenocarcinoma/patología , Neoplasias del Recto/patologíaRESUMEN
OBJECTIVE: The current study evaluated the relationship between serum vitamin C and chronic kidney disease. METHODS: The database from the National Health and Nutrition Examination Survey (NHANES, 2017-2018) was used to perform a cross-sectional study. Multivariate logistic regression was performed to analyze the relationship between serum vitamin C and chronic kidney disease (CKD), and stratified analysis by sex was performed to assess whether there were sex differences in the association between serum vitamin C and CKD. RESULTS: Before stratified analysis, multivariate logistic regression showed that serum vitamin C was negatively associated with CKD in all models (All OR > 1, P< 0.05), the risk of CKD decreased by one quantile increase in serum vitamin C (P for trend< 0.001) and low vitamin C status was associated with a higher risk of CKD (All OR > 1, P< 0.05). Stratified analyses by sex showed that the association between serum vitamin C and CKD remained negative in men, but not in women. CONCLUSION: There were a negative correlation between serum vitamin C and CKD, low levels of vitamin C were associated with a higher risk of CKD, and these associations were only found in men, but not in women.
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Propose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application. Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators. Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR. Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.
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Berberina , Nanopartículas , Berberina/farmacología , Ácido Taurocólico , Liberación de Fármacos , SolubilidadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Coptidis (RC), the dried rhizome of Coptis Chinensis Franch., can dispel dampness and heat within the body and has been traditionally used for the treatment of cardiovascular disease (CVD)-associated problems including hyperlipidemia in China. Berberine (BBR) is the main active component of RC, which has been shown to possess significant therapeutic potential. However, only 0.14% of BBR is metabolized in the liver, and the extremely low bioavailability (<1%) and blood concentration of BBR in experimental and clinical settings is insufficient to achieve the effects as observed under in vitro conditions, which imposes challenges to explain its excellent pharmacological actions. Intense efforts are currently being devoted to defining its specific pharmacological molecular targets, while the exploration from the perspective of its pharmacokinetic disposition has rarely been reported to date, which could hardly make a comprehensive understanding of its hypolipidemic enigma. AIM OF THE STUDY: This study made a pioneering endeavor to unveil the hypolipidemic mechanism of BBR from RC focusing on its unique intestines-erythrocytes-mediated bio-disposition. MATERIALS AND METHODS: The fate of BBR in intestines and erythrocytes was probed by a rapid and sensitive LC/MS-IT-TOF method. To analyze the disposition of BBR, a reliable HPLC method was subsequently developed and validated for simultaneous determination of BBR and its key active metabolite oxyberberine (OBB) in whole blood, tissues, and excreta. Meanwhile, the enterohepatic circulation (BDC) of BBR and OBB was verified by bile duct catheterization rats. Finally, lipid overloading models of L02 and HepG2 cells were employed to probe the lipid-lowering activity of BBR and OBB at in vivo concentration. RESULTS: The results showed that BBR underwent biotransformation in both intestines and erythrocytes, and converted into the major metabolite oxyberberine (OBB). The AUC0-t ratio of total BBR to OBB was approximately 2:1 after oral administration. Besides, the AUC0-t ratio of bound BBR to its unbound counterpart was 4.6:1, and this ratio of OBB was 2.5:1, indicative of abundant binding-type form in the blood. Liver dominated over other organs in tissue distribution. BBR was excreted in bile, while the excretion of OBB in feces was significantly higher than that in bile. Furthermore, the bimodal phenomenon of both BBR and OBB disappeared in BDC rats and the AUC0-t was significantly lower than that in the sham-operated control rats. Interestingly, OBB significantly decreased triglycerides and cholesterol levels in lipid overloading models of L02 and HepG2 cells at in vivo-like concentration, which was superior to the prodrug BBR. CONCLUSIONS: Cumulatively, BBR underwent unique extrahepatic metabolism and disposition into OBB by virtue of intestines and erythrocytes. BBR and OBB were mainly presented and transported in the protein-bound form within the circulating erythrocytes, potentially resulting in hepatocyte targeting accompanied by obvious enterohepatic circulation. The unique extrahepatic disposition of BBR via intestines and erythrocytes conceivably contributed enormously to its hypolipidemic effect. OBB was the important material basis for the hypolipidemic effect of BBR and RC.
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Berberina , Ratas , Animales , Berberina/farmacología , Berberina/uso terapéutico , Extractos Vegetales/farmacología , Triglicéridos/metabolismo , Intestinos , Eritrocitos/metabolismoRESUMEN
INTRODUCTION: AS an uncommon neoplasm, goblet cell adenocarcinoma (GCA) is characterized by mixed endocrine-exocrine features. It is almost exclusively found in the appendix. Primary GCA of the anal canal is extremely rare. CASE PRESENTATION: Herein we describe a novel rare case of 74-year-old Chinese female who is diagnosed with GCA in the anal canal with perianal Paget disease, including a brief review of the literature. In the lesion of anal canal, the tumor was composed of signet-ring-like cells on confluent growth model and copious mucin was produced as well. Simultaneously, the results of immunohistochemistry showed signet-ring-like cells were positive for CK20, CDX2, synaptophysin (Syn), CD56, carcinoembryonic antigen (CEA) and Villin. Meanwhile, the Ki67-labeling index reached 40%. In the lesion of perianal Paget disease, the small groups of atypical neoplastic cells were present in the epidermis. Immunohistochemically, the neoplastic cells were positive for CK20, CDX2 and epithelial membrane antigen, but negative for CK7, GCDFP15, S100, HMB45, and P63. The Ki67-labeling index reached 60% in the most concentrated spot. CONCLUSIONS: Extra-appendiceal GCA was rare and easily under-recognizable. The diagnosis of GCA was seldom made preoperatively. Occasionally, GCA could occur in the anal canal accompanied by perianal Paget disease. So careful rectal examination was important in the patient with perianal Paget disease for avoid missing diagnosis of GCA on anal canal. GCA may show aggressive clinical behavior compared with typical well-differentiated neuroendocrine tumors. Therefore, we should pay more attention on the recognization of this rare disease.
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Adenocarcinoma , Enfermedades del Ano , Neoplasias del Ano , Neoplasias de la Mama , Enfermedad de Paget Extramamaria , Femenino , Humanos , Anciano , Canal Anal/patología , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/patología , Células Caliciformes/metabolismo , Células Caliciformes/patología , Antígeno Ki-67 , Adenocarcinoma/complicaciones , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Neoplasias del Ano/complicaciones , Neoplasias del Ano/diagnóstico , Neoplasias de la Mama/patologíaRESUMEN
Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The pneumocystis jiroveci pneumonia (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients. Patients with de novo AML were enrolled at two hospitals. Daily AQ at established PJP dosing was combined with standard AML therapy, based on the Medical Research Council backbone. AQ compliance, adverse events (AEs), ease of administration score (scale: 1 (very difficult)-5 (very easy)) and blood/marrow pharmacokinetics (PK) were collected during Induction 1. Correlative studies assessed AQ-induced apoptosis and effects on OXPHOS. PDX models were treated with AQ. A total of 26 patients enrolled (ages 7.2 months-19.7 years, median 12 years); 24 were evaluable. A total of 14 (58%) and 19 (79%) evaluable patients achieved plasma concentrations above the known anti-leukemia concentration (>10 µM) by day 11 and at the end of Induction, respectively. Seven (29%) patients achieved adequate concentrations for PJP prophylaxis (>40 µM). Mean ease of administration score was 3.8. Correlative studies with AQ in patient samples demonstrated robust apoptosis, OXPHOS suppression, and prolonged survival in PDX models. Combining AQ with chemotherapy for AML appears feasible and safe in pediatric patients during Induction 1 and shows single-agent anti-leukemic effects in PDX models. AQ appears to be an ideal concomitant AML therapeutic but may require intra-patient dose adjustment to achieve concentrations sufficient for PJP prophylaxis.
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Background and Aims: Histone deacetylase 1 (HDAC1) codes a protein that is a component of the histone deacetylase complex. The abnormal expression of HDAC1 is strongly correlated with cell proliferation, differentiation, transcription, and translation. Through continuous screening of genes associated with changes in lung adenocarcinoma (LUAD), gene networks are formed to explore tumor pathogenesis and new therapeutic targets. Methods: We evaluated HDAC1 gene survival analysis and its expression of LUAD using relevant websites and databases (TCGA and GEO databases). Through data mining, we determined the frequency and type of HDAC1 mutation, obtained the relevant heat map of the gene interaction network, completed the analysis of gene ontology and function enrichment, and understood the pharmaceutic of HDAC1. Results: We found that HDAC1 expression was associated with the prognosis of patients with LUAD. In gene expression analysis, HDAC1 was highly expressed in LUAD, and the HDAC1 interaction gene network (MARCKSL, eIF3I) was closely related to cellular gene expression. Functional network analysis shows that the expression of HDAC1 is related to the monitoring point of the G1-S phase of the cell cycle and the activation of the Notch signaling pathway (CSL transcription factor), which is involved in the process of cell proliferation and differentiation and gene expression associated with new therapeutic targets. Conclusion: Our data revealed the expression and potential regulatory factors of HDAC1 in LUAD of data mining, which laid a foundation for the study of the occurrence, development, and treatment of HDAC1 in LUAD.
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Background: Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC. Methods: The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed. Results: Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage. Conclusion: BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.
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Berberina , Ratones , Ratas , Animales , Distribución Tisular , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Macrófagos , EritrocitosRESUMEN
In this paper, we propose a reconfigurable metadevice with independent polarization control based on a 90° rotationally symmetric microstructure. Three functionalities of broadband high-efficiency transmission, broadband high-efficiency reflection, and perfect absorption are switched by the on-state and off-state PIN diodes. Coding metadevices designed with diversified lumped element combinations are further studied in detail. By controlling the two diodes on the top layer in opposite states, absorption bandwidth is significantly improved. Reasonable arrangements of coding sequences allow for reflected dual/multi-beam modulation. Electric field distribution, power loss, complex impedance functions, and equivalent circuit models are used to better analyze the physical mechanism of the design. A prototype of the microstructure has been fabricated, and the experimental results agree well with the simulation. Electronic components integrated microstructures with high degrees of freedom have potential applications in intelligent wireless communication, electronic detection, advanced sensors, and smart stealth radomes.
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Dye-containing wastewater discharge from the textile industry poses a serious pollution hazard that can be overcome by eliminating the washing step following the dyeing process. To study the washing-free printing of disperse dye ink, a number of water-borne polymers were selected and added to the ink, and the properties of the inks were discussed. By optimizing the ink formulation, printed fabrics with high color strength and color fastness were produced. The effects of the addition of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and polyethylene glycol (PEG) on the ink jetting performance and printing performance were intensively investigated. The migration-diffusion-fixation behavior of disperse dyes in inks on the polyester fiber was explored. The disperse dye ink with 0.075 wt.% PVA exhibited the strongest migration-diffusion effect. The PVA ink exhibited excellent jetting performance and printing color fastness, and the printing color strength was better than that of the PVP and PEG ink. The addition of PVA increased the difference between the solubility parameter of the disperse dyes and ink system, which improved the migration of disperse dyes from the ink system to the polyester fabric. Meanwhile, PVA could form a protective layer on printed fabrics because of its excellent film-forming properties at room temperature. The washing-free inkjet printing method developed in this study provides a theoretical basis for screening water-borne polymers and an environmentally friendly pathway for the printing of textiles.
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In this paper, a reconfigurable all-dielectric metasurface based on Ge2Sb2Se4Te1 (GSST) phase-change material is proposed. By changing GSST from amorphous state to crystalline state, the metasurface can achieve high circular dichroism (CD) and wideband polarization conversion for circularly polarized waves in the mid-infrared (MIR) band. The maximum CD value reaches 0.95 at 74 THz, and circular polarization conversion efficiency is more than 90% in the wideband range of 41 THz - 48 THz. In addition, based on Pancharatnam-Berry phase, three kinds of wavefront manipulation of light have been realized: abnormal refraction, orbital angular momentum vortex beam and orbital angular momentum vortex beam splitting. This work has potential applications in the future MIR optical integrated system.
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Background: Although emerging evidence supports the relationship between necroptosis (NEC) related genes and hepatocellular carcinoma (HCC), the contribution of these necroptosis-related genes to the development, prognosis, and immunotherapy of HCC is unclear. Methods: The expression of genes and relevant clinical information were downloaded from TCGA-LIHC, LIRI-JP, GSE14520/NCI, GSE36376, GSE76427, GSE20140, GSE27150, and IMvigor210 datasets. Next, we used an unsupervised clustering method to assign the samples into phenotype clusters base on 15 necroptosis-related genes. Subsequently, we constructed a NEC score based on NEC phenotype-related prognostic genes to quantify the necroptosis related subtypes of individual patients. Results: We divided the samples into the high and low NEC score groups, and the high NEC score showed a poor prognosis. Simultaneously, NEC score is an effective and stable model and had a good performance in predicting the prognosis of HCC patients. A high NEC score was characterized by activation of the stroma and increased levels of immune infiltration. A high NEC score was also related to low expression of immune checkpoint molecules (PD-1/PD-L1). Importantly, the established NEC score would contribute to predicting the response to anti-PD-1/L1 immunotherapy. Conclusions: Our study provide a comprehensive analysis of necroptosis-related genes in HCC. Stratification based on the NEC score may enable HCC patients to benefit more from immunotherapy and help identify new cancer treatment strategies.
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Silk, a natural protein fiber, is widely used in the textile industry and biomedical materials for its excellent properties. However, its application in some fields is seriously restricted due to its poor anti-wrinkle behavior. In this study, 2,4,6-trichloropyrimidine (TLP) was used in the production of anti-wrinkle silk fabrics. The optimum finishing conditions were as follows: 3-g/L 2,4,6-trichloropyrimidine, 6-g/L NaHCO3, 8-g/L Na2SO4, finishing temperature of 65 °C, and finishing time of 40 min. The crease recovery angle of the finished fabric is 16-20% higher than the unfinished fabric, and the finishing process has a small effect on the whiteness of silk while achieving some degree of washing resistance. The morphology and chemical structures of the finished silk fabric were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The K/S value of the finished silk fabric dyed with reactive dyes increased compared with the silk fabric only dyed, indicating that the dyeability of the finished fabric was improved. This technology provides a new method for fabricating silk color crease-resistant fabrics.