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1.
ACS Omega ; 9(27): 29274-29281, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39005804

ABSTRACT

For antibacterial purposes, a photothermal and photodynamic antibacterial membrane was prepared through electrospinning. We used zein as the substrate and introduced Protoporphyrin IX (PpIX) into the protein structure. Then, we used electrospinning technology to weave the modified zein into a fiber structure. We finally introduced a metallic polyphenol network (MPN) coating on the fiber surface to form the final membrane: MPN@Zein-PpIX. Then, we investigated the photothermal and photodynamic properties of the membrane and assessed its antibacterial activity with in vitro agar plate counting methods. The MPN@Zein-PpIX membrane exhibited good singlet oxygen generation and excellent photothermal conversion. Additionally, it showed good antibacterial capacity in vitro, owing to the combination of photothermal and photodynamic properties. Our research provides a simple approach to prepare a multifunctional membrane with excellent antibacterial ability. We used the electrospinning technique to anchor PpIX onto zein to produce a fiber membrane (Zein-PpIX) that can be adhered in situ to improve the biocompatibility of PpIX, and the MPN makes the membrane surface more hydrophilic and more accessible to adhere to biological tissues. The MPN@Zein-PpIX membrane provided new ideas for combining PDT and PTT, and it had great potential for use in the antibacterial application field.

2.
Basic Clin Pharmacol Toxicol ; 135(2): 148-163, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38887973

ABSTRACT

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver. Here, we investigated the metabolism activity of CYP1A2, CYP3A1/2 and CYP2C6/11 during PXR activation-induced liver enlargement and regeneration in rats after cocktail dosing of CYP probe drugs. For PCN-induced hepatomegaly, a notable increase in the metabolic activity of CYP3A1/2 and CYP2C6/11, as evidenced by the plasma exposure of probe substrates and the AUC ratios of the characteristic metabolites to its corresponding probe substrates. The metabolic activity of CYP1A2, CYP3A1/2 and CYP2C6/11 decreased significantly after PHx. However, PCN treatment obviously enhanced the metabolic activity of CYP2C6/11 and CYP3A1/2 in PHx rats. Furthermore, the protein expression levels of CYP3A1/2 and CYP2C6/11 in liver were up-regulated. Taken together, this study demonstrates that PXR activation not only induces hepatomegaly and liver regeneration in rats, but also promotes the protein expression and metabolic activity of the PXR downstream metabolizing enzymes such as CYP3A1/2 and CYP2C6/11 in the body.


Subject(s)
Cytochrome P-450 CYP3A , Hepatomegaly , Liver Regeneration , Liver , Pregnane X Receptor , Pregnenolone Carbonitrile , Animals , Pregnane X Receptor/metabolism , Pregnane X Receptor/genetics , Liver Regeneration/drug effects , Male , Cytochrome P-450 CYP3A/metabolism , Pregnenolone Carbonitrile/pharmacology , Liver/metabolism , Liver/enzymology , Liver/drug effects , Rats , Hepatomegaly/metabolism , Hepatomegaly/pathology , Aryl Hydrocarbon Hydroxylases/metabolism , Aryl Hydrocarbon Hydroxylases/genetics , Cytochrome P450 Family 2/metabolism , Cytochrome P450 Family 2/genetics , Rats, Sprague-Dawley , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP1A2/genetics , Steroid 16-alpha-Hydroxylase/metabolism , Steroid 16-alpha-Hydroxylase/genetics , Steroid 12-alpha-Hydroxylase/metabolism , Steroid 12-alpha-Hydroxylase/genetics , Hepatectomy
3.
Drug Metab Dispos ; 52(7): 597-605, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38697851

ABSTRACT

Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist pregnenolone 16α-carbonitrile (PCN) for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbia. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP, and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiments further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly. SIGNIFICANCE STATEMENT: This work describes that the composition of gut microbiota is altered in mouse pregnane X receptor (PXR) agonist pregnenolone 16α-carbonitrile (PCN)-induced hepatomegaly. Treatment with an antibiotic cocktail depletes the intestinal microbiota, leading to the impairment of liver enlargement caused by PCN. Additionally, fecal microbiota transplantation from PCN-treated mice induces liver enlargement. Further study revealed that gut microbiota is involved in hepatomegaly via regulating PXR and yes-associated protein activation.


Subject(s)
Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Hepatomegaly , Mice, Inbred C57BL , Pregnane X Receptor , Pregnenolone Carbonitrile , YAP-Signaling Proteins , Animals , Hepatomegaly/chemically induced , Hepatomegaly/metabolism , Pregnane X Receptor/agonists , Pregnane X Receptor/metabolism , Gastrointestinal Microbiome/drug effects , Mice , Pregnenolone Carbonitrile/pharmacology , YAP-Signaling Proteins/metabolism , Male , Fecal Microbiota Transplantation/methods , Liver/drug effects , Liver/metabolism
4.
Opt Lett ; 49(6): 1595-1598, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489459

ABSTRACT

In the realm of metasurface-based polarimetry, well-known for its remarkable compactness and integration capabilities, previous attempts have been hindered by limitations such as the restricted choices of target polarization states and the inefficient focusing of light. To address these problems, this study introduces and harnesses a novel, to our knowledge, forward-solving model, grounded in the equivalence principle and dyadic Green's function, to inversely optimize the vectorial focusing patterns of metalenses. Leveraging this methodology, we develop and experimentally validate a single multi-foci metalens-based polarimeter, capable of simultaneously separating and concentrating four distinct elliptical polarization states at a wavelength of 10.6 µm. Rigorous experimental evaluations, involving the assessment of 18 scalar polarized beams, reveal an average error of 5.92% and a high contrast ratio of 0.92, which demonstrates the efficacy of the polarimeter. The results underscore the potential of our system in diverse sectors, including military defense, healthcare, and autonomous vehicle technology.

5.
Altern Ther Health Med ; 30(1): 160-166, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37773668

ABSTRACT

Objective: To investigate the long-term safety and efficacy of autologous peripheral blood stem cell transplantation (APBSCT) in treating decompensated hepatitis B cirrhosis. Methods: In this study, a retrospective analysis was conducted on a cohort of 84 patients diagnosed with decompensated hepatitis B cirrhosis between January 2011 and December 2012. The patients were categorized into two groups based on their treatment approach: the transplantation group, consisting of 34 cases who received APBSCT in addition to medical treatment, and the comprehensive medical treatment (CMT) group, comprising 50 cases who solely received CMT. EPI Data software was used for data input and verification. Survival curves were drawn by Kaplan-Meier method and analyzed by log-rank test. Paired t test and independent sample t test were used for intra-group and inter-group mean comparison of measurement data, respectively. The Mann-Whitney U test is used for non-normally distributed data. Results: After the ten-year follow-up period, it was found that overall survival (OS) in the transplantation group was markedly higher than that in the CMT (56% vs. 16%, P < .001). Albumin (ALB), prothrombin time (PT), and indocyanine green retention at 15 min (ICG R15) were significantly improved in sequence at 4 to 12 weeks of early treatment in APBSCT group; subsequently, the Acoustic radiation force impulse (ARFI) index and spleen length significantly decreased at 48 weeks. Compared with the CMT group, ALB and PT levels in the APBSCT group continued to recover and eventually stabilize at normal or low-risk levels at subsequent follow-ups up to 8 years. The ten-year prevalence of hepatocellular carcinoma (HCC) in the APBSCT group was markedly lower than that in the CMT group (26% vs. 62%; P = .025). Moreover, APBSCT significantly reduced ascites (χ2 = 6.997, P = .041) and was not associated with any significant adverse events during APBSCT. Based on clinical evidence, APBSCT is a safe and effective treatment for decompensated hepatitis B cirrhosis, resulting in a favorable long-term prognosis with no significant adverse events. Conclusions: APBSCT is a relatively safe and effective treatment for decompensated hepatitis B cirrhosis.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Peripheral Blood Stem Cell Transplantation , Humans , Peripheral Blood Stem Cell Transplantation/methods , Retrospective Studies , Hepatitis B/complications , Hepatitis B/diagnosis , Liver Cirrhosis/therapy , Liver Cirrhosis/diagnosis
7.
Article in English | MEDLINE | ID: mdl-37944965

ABSTRACT

Objective: In recent years, stem cell transplantation (SCT) has been applied to the clinical treatment of patients with cirrhosis. The specialist clinic of the SCT clinic provides regular and effective interventions for cirrhosis, helping to improve patient management and compliance. The aim of this study was to determine the efficacy and safety of SCT in the treatment of cirrhosis. Methods: This systematic review adhered to the guidelines outlined in the PRISMA statement. The National Library of Medicin (MEDLINE), Excerpt Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical Trials.gov databases were searched to screen liver cirrhosis-related articles with stem cell therapy from 2000 to 2022. The articles were then filtered and extracted for clinical outcomes including MELD score, Child-Pugh score, platelets, creatinine, bilirubin, albumin, international normalized ratio (INR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), α fetoprotein (AFP), prothrombin time (PT). The data were normalized and analyzed using the standardized mean difference (SMD) and 95% confidence interval (CI). Results: A total of 1209 articles were searched, and from these, ten studies were selected for analysis regarding the association between SCT and the clinical outcomes of liver cirrhosis. The findings revealed that SCT therapy, in comparison to conventional treatment, resulted in a reduction in MELD score and INR after 1 month, a decrease in Child-Pugh score at 3 months, an increase in platelet count at 3 months, and an elevation in ALB levels after 1 month. However, no significant beneficial effects were observed on creatinine, bilirubin, PT, ALT, AST, GGT, ALP, and ASP levels. Conclusion: This study suggested that SCT therapy could elevate the ALB levels and alleviate the MELD score and INR, short-term decreasing the Chile-Pugh score and increasing the platelet levels. It could be a potential therapeutic alternative for patients with cirrhosis.

8.
ACS Omega ; 7(38): 33821-33829, 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36188296

ABSTRACT

To reduce the drug resistance of bacteria and enhance the antibacterial ability in bacterial infection therapy, we designed a new antibacterial nanoagent. In this system, a photosensitizer (indocyanine green, ICG) was loaded in bovine serum albumin (BSA) through hydrophobic-interaction-induced self-assembly to form stable BSA@ICG nanoparticles. Furthermore, a positively charged antibacterial peptide bacitracin (Bac) was physically immobilized onto the surface of BSA@ICG to generate a bacterial-targeted nanomedicine BSA@ICG@Bac through electrostatic interactions. Afterward, its photodynamic and photothermal activities were intensely evaluated. Moreover, its bactericidal efficiency was assessed via in vitro antibacterial assays and bacterial biofilm destruction tests. First, the obtained BSA@ICG@Bac showed both good singlet oxygen generation property and high photothermal conversion efficiency. In addition, it showed enhanced photodynamic and photothermal antibacterial capacities and biofilm-removing ability in vitro due to Bac modification. To sum up, our research provided an economic and less-time-consuming approach to preparing antibacterial nanomedicines with excellent antibacterial ability. Therefore, the prepared antibacterial nanomedicines have great potential to be utilized in clinical trials in the future.

9.
BMC Geriatr ; 22(1): 632, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35915396

ABSTRACT

BACKGROUND: Falls are an important cause of injury and death of older people. Hence, analyzing the multifactorial risk of falls from past cases to develop multifactorial intervention programs is clinically significant. However, due to the small sample size, there are few studies on fall risk analysis of clinical characteristics of fallers, especially among older hospitalized patients. METHODS: We collected data on 153 inpatients who fell (age ≥ 60 years) from the hospital nursing adverse event reporting system during hospitalization at Shandong Provincial Hospital Affiliated to Shandong First Medical University, China, from January 2018 to December 2020. Patient characteristics at the time of the fall, surrounding environment, primary nurse, and adverse fall events were assessed. The enumeration data were expressed as frequency and percentage, and the chi-squared was performed between recurrent fallers and single fallers, and non-injurious and injurious fall groups. RESULTS: Cross-sectional data showed 18.3% of the 153 participants experienced an injurious fall. Compared with single fallers, a large proportion of older recurrent fallers more often experienced preexisting conditions such as cerebrovascular disease or taking hypoglycemic drugs. They were exposed to higher risks and could experience at least 3 fall times in 3 months. Besides, the credentials of their responsible nurses were often higher. Factors that increased the risk of a fall-related injury were hypoglycemic drugs (OR 2.751; 95% CI 1.114-6.795), and nursing adverse events (OR 47.571; 95% CI 14.392-157.247). Older inpatients with bed rails (OR 0.437; 95% CI 0.190-1.005) or falling at the edge of the bed (OR 0.365; 95% CI 0.138-0.964) were less likely to be injured than those without bed rails or not falling at the edge of the bed. Fall risks were significantly correlated with more severe fall-related injuries. Older patients with moderate (OR 5.517; CI 0.687-44.306) or high risk (OR 2.196; CI 0.251-19.219) were more likely to experience fall-related injuries than those with low risk. CONCLUSIONS: Older inpatient falls are an ongoing challenge in hospitals in China. Our study found that the incidence of fall-related injuries among inpatients aged ≥ 60 years remained at a minor level. However, complex patient characteristics and circumstances can contribute to fall-related injuries. This study provides new evidence on fall-related injuries of older inpatients in China. Based on the factors found in this study, regular fall-related injury epidemiological surveys that investigate the reasons associated with the injuries were crucial when considering intervention measures that could refine fall-related injuries. More prospective studies should be conducted with improved and updated multidisciplinary fall risk assessment and comprehensive geriatric assessment as part of a fall-related injury prevention protocol.


Subject(s)
Accidental Falls , Inpatients , Accidental Falls/prevention & control , Aged , Cross-Sectional Studies , Hospitals , Humans , Hypoglycemic Agents , Incidence , Prospective Studies , Risk Factors
12.
Mol Ther Nucleic Acids ; 19: 1134-1144, 2020 Mar 06.
Article in English | MEDLINE | ID: mdl-32059339

ABSTRACT

Circular RNAs (circRNAs) are a class of noncoding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. However, the molecular mechanisms that link circRNAs with progression of papillary thyroid carcinoma (PTC) are not well understood. In the present study, the function of circ_0006156 (circFNDC3B) was investigated in human PTC cells. First, we detected the expression of circFNDC3B in PTC tissues and PTC cell lines by RT-PCR. A luciferase reporter assay and AGO2-RNA immunoprecipitation (RIP) was used to confirm the relationship between circFNDC3B and microRNA (miR)-1178. PTC cells were stably transfected with small interfering RNA (siRNA) against circFNDC3B, and cell proliferation, migration, and invasion were detected to evaluate the effect of circFNDC3B in PTC, while tumorigenesis was assayed in nude mice. In this study, circFNDC3B was observed to be upregulated in PTC tissues and cell lines. Knockdown of circFNDC3B inhibited cell proliferation and promoted cell apoptosis in PTC cells. Bioinformatics analysis predicted that there is a circFNDC3B/miR-1178/Toll-like receptor 4 (TLR4) axis in PTC. The dual-luciferase reporter system validated the direct interaction of circFNDC3B, miR-1178, and TLR4. Furthermore, circFNDC3B facilitates PTC progression in vivo. Importantly, we demonstrated that circFNDC3B was upregulated in serum exosomes from PTC patients. In summary, our study demonstrated that circFNDC3B modulates PTC progression through the miR-1178/TLR4 pathway. Our findings indicated that circFNDC3B may serve as a promising therapeutic target for the treatment of PTC patients.

13.
Mol Ther Nucleic Acids ; 19: 1153-1163, 2020 Mar 06.
Article in English | MEDLINE | ID: mdl-32059341

ABSTRACT

Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with progression of papillary thyroid carcinoma (PTC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for PTC from the aspect of circRNA-miRNA-mRNA interaction. We investigated the expression of circRNAs in five paired PTC tissues and normal tissues by microarray analysis. The circRNA microarray assay followed by qRT-PCR was used to verify the differential expression of hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. The qRT-PCR analysis was to investigate the expression pattern of circRASSF2 in PTC tissues and cell lines. Then the effects of circRASSF2 on cell proliferation and apoptosis were assessed in PTC in vitro. Furthermore, bioinformatics online programs predicted and luciferase reporter assays were used to validate the association of circRASSF2 and miR-1178 in PTC cells. In this study, circRASSF2 was observed to be upregulated in PTC tissues and cell lines. Knockdown of circRASSF2 inhibited cell proliferation and promoted cell apoptosis in PTC cells. Bioinformatics analysis predicted that there is a circRASSF2/miR-1178/TLR4 axis in PTC. A dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-1178, and TLR4. Furthermore, circRASSF2 facilitates PTC progression in vivo. Importantly, we demonstrated that circRASSF2 was upregulated in serum exosomes from PTC patients. In summary, our study demonstrates that circRASSF2 modulates PTC progression through the miR-1178/TLR4 pathway. Our findings indicate that circRASSF2 may serve as a promising therapeutic target for the treatment of PTC patients.

14.
J Cell Biochem ; 120(2): 1860-1868, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30171715

ABSTRACT

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, and its incidence is on the rise. It has been reported that some matrix metalloproteinases (MMPs) are abnormally expressed in PTC and can be used as diagnostic markers. However, few studies have explored the underlying mechanisms by which MMPs promote tumor progression. In this study, we used microarray analysis to compare the variations of gene expression within the PTC cell populations and their adjacent normal tissues and found that MMP-11 was the most differentially expressed MMP. To investigate the role of MMP-11 in the mediation of thyroid cancer cell development, pEnter-MMP-11 plasmid, and MMP-11 small interfering RNA were applied to up- and downregulate MMP-11 expression of in cultured PTC cell lines K1 and BCPAP. The results suggested that the levels of proliferation and migration of cells transfected with MMP-11 siRNA were significantly reduced, while the levels in MMP-11-plasmid-transfected cells were increased. In terms of the mechanism, experimental data showed that the change in cyclin D1 is consistent with MMP-11 expression, which may explain the changes in proliferation. In addition, Western blot assay was conducted to analyze the p65 and activated (phospho-) p65 protein levels concomitant with MMP-11 adjustments. Variations in intracellular MMP-11 significantly altered the amount of phospho-p65 in thyroid cells, while p65 knockdown did not affect MMP-11 expression. These results suggest that MMP-11 is located upstream of p65 and regulates its activity. Interestingly, the data for the Transwell assay suggested that MMP-11 regulatory migration is also associated with the NF-κB p65 signaling pathway. In conclusion, this report describes the important role of MMP-11 in the regulation of thyroid cell proliferation and migration. Mechanistic studies have shown that cyclin D1 and p65 are important mediators in the processes, which provides a new way to study the mechanism of MMPs promoting the progression of thyroid cancer.

15.
Cell Physiol Biochem ; 47(5): 2077-2087, 2018.
Article in English | MEDLINE | ID: mdl-29975932

ABSTRACT

BACKGROUND/AIMS: Breast cancer (BC) is the most common cancer in women worldwide. Despite great advancements in cancer therapy in recent years, surgery and chemotherapy are still the mainstays of BC treatment. However, cancer cells usually develop mechanisms to evade cell death induced by chemotherapy. Thus, strategies are needed to reverse the chemoresistance of cancer cells. METHODS: We established cisplatin-resistant BC models in MDA-MB-231 and MCF-7 BC cell lines through long-term exposure to cisplatin. Quantitative reverse transcription PCR was used to examine the expression of microRNA (miR)-100. MTT cell viability assays were performed to determine cell viability. Regulation of hematopoietic cell-specific protein 1-associated protein X-l (HAX-1) targeted by miR-100 was confirmed by western blotting and luciferase reporter assays. The mitochondrial membrane potential and apoptosis were measured by flow cytometry. Release of cytochrome c from the mitochondria into the cytoplasm, HAX-1 expression, and activation of caspase-9 and caspase-3 were detected by western blotting. RESULTS: A clear decrease in miR-100 expression was observed in cisplatin-resistant MDA-MB-231 and MCF-7 cells (MDA-MB-231/R and MCF-7/R). Overexpression of miR-100 increased the sensitivity of MDA-MB-231/R and MCF-7/R cells to cisplatin treatment and promoted cisplatin-induced mitochondrial apoptosis by targeting HAX-1 gene. CONCLUSIONS: MiR-100 targeted HAX-1 to increase the chemosensitivity of BC by mediating the mitochondrial apoptosis pathway.


Subject(s)
Apoptosis/drug effects , Breast Neoplasms/drug therapy , Cisplatin/pharmacology , Drug Resistance, Neoplasm , MicroRNAs/biosynthesis , RNA, Neoplasm/biosynthesis , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans , MCF-7 Cells , Mice , Mice, Nude , MicroRNAs/genetics , Mitochondria/genetics , Mitochondria/metabolism , Mitochondria/pathology , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , RNA, Neoplasm/genetics
16.
Oncol Rep ; 38(2): 1287-1294, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28677753

ABSTRACT

Papillary thyroid carcinoma is the most common thyroid cancer and the incidence is increasing. Aberrant activation of the WNT/ß­catenin pathway plays an important role in carcinogenesis. In the present study, microarray analysis was employed to compare tissues from papillary thyroid cancer and adjacent normal tissues to determine candidate genes facilitating tumor invasion. The result demonstrated that genes involved in WNT/ß­catenin signaling pathway were activated in papillary thyroid cancer, WNT10A expression was found to be upregulated >4-fold. The variations in gene expression were verified in tissues obtained from other papillary thyroid cancer patients. Molecular mechanism exploration in thyroid cells showed that enhanced WNT10A/ß­catenin signaling pathway activation promoted cell proliferation and migration. The promotion was validated by RNA interference of WNT10A and LEF1 expression. Moreover, results from flow cytometry demonstrated that WNT/ß­catenin signaling pathway activation reduced the percentage of late apoptotic thyroid cells. Conclusively, the results suggest for the first time that WNT10A/ß­catenin signaling pathway plays a crucial role in human papillary thyroid cancer.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Papillary/pathology , Cell Transformation, Neoplastic/pathology , Lymphoid Enhancer-Binding Factor 1/metabolism , Thyroid Neoplasms/pathology , Wnt Proteins/metabolism , beta Catenin/metabolism , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Papillary/genetics , Carcinoma, Papillary/metabolism , Case-Control Studies , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Lymphoid Enhancer-Binding Factor 1/genetics , Prognosis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Tumor Cells, Cultured , Wnt Proteins/genetics , beta Catenin/genetics
17.
Kidney Blood Press Res ; 42(2): 294-303, 2017.
Article in English | MEDLINE | ID: mdl-28531894

ABSTRACT

BACKGROUND/AIMS: To assess the prognostic accuracy of absolute serum creatinine (sCr) changes ('Delta-sCr') on the long-term outcomes in cirrhotic patients, and evaluate the performance of the 'Delta-sCr' approach to stage acute kidney injury (AKI), compared with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. METHODS: We conducted a retrospective analysis of 333 hospitalized patients. We classified AKI stages using two methods: 1) KDIGO AKI criteria; 2) 'Delta-sCr' system, defined by the difference between the baseline and the peak sCr value during the hospitalization. The end point was the hazard of 1-year death. RESULTS: The prevalence of AKI in cirrhotic patients was 18.01% by the KDIGO criteria, and 25.22% by the 'Delta-sCr' system. On multivariable Cox hazard analysis, both of the two methods were independent predictive factors of death ('Delta-sCr' system: OR=2.911, p<0.001), (KDIGO criteria: OR=2.065, p<0.001). However, the 'Delta-sCr' system provided a modest improvement in classification over the KDIGO criteria with a net reclassification improvement (NRI) of 28.7% (p<0.001) and integrated discrimination improvement (IDI) of 7.5% (p=0.03). And the predictive value of the 'Delta-sCr' system could be significantly improved (p=0.006), when combined with age and MELD score. CONCLUSION: The Delta-sCr is associated with the 1-year mortality. And the 'Delta-sCr' system may optimize the discrimination of risk prediction.


Subject(s)
Acute Kidney Injury/pathology , Creatinine/blood , Fibrosis , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Adult , Aged , Female , Hospitalization , Humans , Male , Middle Aged , Patient Outcome Assessment , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment
18.
Oncotarget ; 8(7): 11621-11628, 2017 Feb 14.
Article in English | MEDLINE | ID: mdl-28086227

ABSTRACT

The aim of this study was to investigate the protective effects of matrine on lipopolysaccharide (LPS)-induced inflammation and oxidative stress in vivo and in vitro. The results showed that matrine improved intestinal inflammatory status and oxidative balance and enhanced chemokine receptor 7 (CCR7) expression. In LPS-challenged mice and Caco-2 cells, matrine alleviated LPS-induced inflammation and oxidative stress via downregulating pro-inflammatory cytokines (IL-1ß and IL-17) and malondialdehyde (MDA) production. CCR7-siRNA transfection blocked the protective effects of matrine on LPS-induced inflammation and oxidative stress and exacerbated LPS caused injury. In conclusion, matrine alleviates LPS-induced intestinal inflammation and oxidative stress in mice and Caco-2 cells, which may be associated with CCR7 signal.


Subject(s)
Alkaloids/pharmacology , Intestinal Mucosa/metabolism , Intestines/drug effects , Lipopolysaccharides/pharmacology , Oxidative Stress/drug effects , Quinolizines/pharmacology , Receptors, CCR7/metabolism , Animals , Anthelmintics/pharmacology , Caco-2 Cells , Drug Interactions , Female , Humans , Inflammation/metabolism , Inflammation/pathology , Intestines/pathology , Mice , Mice, Inbred BALB C , Random Allocation , Matrines
19.
Hepatol Res ; 47(4): 347-358, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27283374

ABSTRACT

AIM: Chronic hepatitis B-associated liver failure (CHB-LF) is associated with high mortality. Antiviral therapy with nucleoside and nucleotide analogs (NUCs) has been reported to improve the short-term prognosis of patients with CHB-LF. However, the long-term effects of the therapy remain unclear. We undertook a cohort study to investigate the long-term effect of NUC-based antiviral therapy in patients with CHB-LF. METHODS: A total of 976 patients with CHB-LF were enrolled between January 2001 and December 2009 at the Liver Disease Center of Ningbo No. 2 Hospital (Ningbo, China). The patients were divided into the NUC treatment group (n = 412) and control group (n = 564). The propensity score matching method was used to match the patients between the two groups to equilibrate the covariates. Survival analysis was carried out using the matched samples. The Cox proportional hazard model was used for the analysis of prognostic factors. RESULTS: After propensity matching, 262 pairs were successfully matched. No statistically significant difference was observed in the baseline characteristics of the matching pairs (P > 0.05). The long-term survival rate and survival duration of the NUC treatment group were higher than that of the control group (P < 0.05). Gender, age, Model for End-stage Liver Disease values, cholinesterase levels, white blood cell counts, hepatic encephalopathy, concomitant infection, and treatment with NUCs were found to be the independent factors associated with long-term prognosis. CONCLUSION: Antiviral therapy with NUCs may reduce the mortality rate and improve the long-term prognosis of patients with CHB-LF.

20.
J Sep Sci ; 39(21): 4136-4146, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27612098

ABSTRACT

A simple procedure for the synthesis of three new oxazolinyl-substituted ß-cyclodextrins (6-deoxy-6-R-(-)-4-phenyl-4,5-dihydrooxazolinyl-ß-cyclodextrin, 6-deoxy-6-S-(-)-4-phenyl-4,5-dihydrooxazolinyl-ß-cyclodextrin, and 6-deoxy-6-S-(-)-(4-pyridin-1-ium-4-methyl-benzenesulphonate)-4,5-dihy-drooxazolinyl-ß-cyclodextrin) and their covalent bonding to silica are reported. The ability of these chiral stationary phase columns for separating compounds is also presented and discussed. Twenty-eight compounds were examined in the polar-organic mobile phase mode, and 11 ß-nitroethanols were tested in the reversed-phase mode. Excellent enantioseparations were achieved for most of the analytes, even for several challenging compounds. The rigid and flexible structures of mono-substituted chiral groups and the fragments around the rim of the ß-cyclodextrin cavity played an important role in the separation process. Factors such as π-π stacking, dipole-dipole interactions, ion-pairing, and steric hindrance effects were found to affect the chromatographic performance. Moreover, the buffer composition, and percentages of organic modifiers in the mobile phase, were investigated and compared. The mechanisms involved in the separation were postulated based on the chromatographic data.

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