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1.
Immunology ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38618976

ABSTRACT

Despite progress in cancer immunotherapy, ovarian cancer (OC) prognosis continues to be disappointing. Recent studies have shed light on how not just tumour cells, but also the complex tumour microenvironment, contribute to this unfavourable outcome of OC immunotherapy. The complexities of the immune microenvironment categorize OC as a 'cold tumour'. Nonetheless, understanding the precise mechanisms through which the microenvironment influences the effectiveness of OC immunotherapy remains an ongoing scientific endeavour. This review primarily aims to dissect the inherent characteristics and behaviours of diverse cells within the immune microenvironment, along with an exploration into its reprogramming and metabolic changes. It is expected that these insights will elucidate the operational dynamics of the immune microenvironment in OC and lay a theoretical groundwork for improving the efficacy of immunotherapy in OC management.

2.
Angew Chem Int Ed Engl ; 63(12): e202315222, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38299697

ABSTRACT

A new electrochemical transformation is presented that enables chemists to couple simple alkyl carboxylic acid derivatives with an electrophilic amine reagent to construct C(sp3 )-N bond. The success of this reaction hinges on the merging of cooperative electrochemical reduction with nickel catalysis. The chemistry exhibits a high degree of practicality, showcasing its wide applicability with 1°, 2°, 3° carboxylic acids and remarkable compatibility with diverse functional groups, even in the realm of late-stage functionalization. Furthermore, extensive mechanistic studies have unveiled the engagement of alkyl radicals and iminyl radicals; and elucidated the multifaceted roles played by i Pr2 O, Ni catalyst, and electricity.

3.
Clin Cosmet Investig Dermatol ; 17: 147-158, 2024.
Article in English | MEDLINE | ID: mdl-38283796

ABSTRACT

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p<0.01), cutaneous inflammatory infiltration (p<0.01), and CD8α-positive expression (p<0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p<0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p<0.05, p<0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p<0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p<0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.

4.
Talanta ; 270: 125567, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38171237

ABSTRACT

Water in organic solvents is a prevalent impurity that significantly influences chemical reactions and industrial processes. Carbon dots (CDs) gained attention as promising tools for chemosensing due to their advantageous characteristics, including easy synthesis, cost-effectiveness, and excellent adjustability and stability. However, limited solubility in water and turn off fluorescence response mode hinder the practical utilization of CDs for water sensing. To tackle such dilemma, a highly water-soluble CDs with distinctive hydrogen-bond-induced emission (HBIE) was rationally designed through introducing sulfone group into the widely employed p-phenylenediamine precursor. The inclusion of sulfone group imparts the CDs with notable water solubility, as well as distinctive ratiometric fluorescent response towards water content, exhibiting high sensitivity and selectivity. Upon exposure to water, the emission color of CDs undergoes a real-time transition from blue to yellow-green, which can be readily discerned by naked eyes. The CDs have been successfully applied in detecting water in commercially available alcohol. This study presents a straightforward yet efficacious approach for rationally design of CDs with unique HBIE characteristics and ratiometric fluorescent response, offering great potential for practical chemosensing applications.

5.
Technol Health Care ; 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-38073344

ABSTRACT

BACKGROUND: Despite the advancement of new screening strategies and the advances in pharmacological therapies, the cancerization rates of familial adenomatous polyposis (FAP) are stable and even increased in the last years. Therefore, it necessitates additional research to characterize and understand the underlying mechanisms of FAP. OBJECTIVE: To determine the genes that drive the pathogenesis of familial adenomatous polyposis (FAP). METHODS: We performed on a cohort (GSE111156) gene profile, which consist of four group of gene expressions (the gene expressions of cancer, adenoma and normal tissue of duodenal cancer from patients with FAP were defined as Case N, Case A and Case C respectively, while that of adenoma tissue from patients with FAP who did not have duodenal cancer was Ctrl A). Tracking Tumor Immunophenotype (TIP) website was applied to reveal immune infiltration profile and signature genes of FAP. We merged the genes of key module (pink and midnight module) with signature genes to obtained the biomarkers related with FAP pathogenesis. The expression of these five biomarkers in FAP intratumoral region (IT) and tumor rim (TR) was detected with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: In total, 220, 23 and 63 DEGs were determined in Cases C, A and N, in comparison to Ctrl A. In total, 196 and 10 DEGs were determined in Cases C and A, separately, as compared to Case N. A total of four biomarkers including CCL5, CD3G, CD2 and TLR3 were finally identified associated with pink module, while only one biomarker (KLF2) associated with midnight module was identified. All biomarkers were evidently raised in FAP IT tissues utilizing qRT-PCR. CONCLUSION: We identified five potential biomarkers for pathogenesis of FAP to understand the fundamental mechanisms of FAP progression and revealed some probable targets for the diagnosis or treatment of FAP.

6.
Mol Immunol ; 161: 33-43, 2023 09.
Article in English | MEDLINE | ID: mdl-37481827

ABSTRACT

Psychological stress triggers onset and development of vitiligo in humans. However, the mechanism of psychological stress on vitiligo remains unclear. The study aims to investigate whether psychological stress promotes vitiligo and explore the underlying mechanism. A depigmentation mouse model induced by applying a skin-bleaching reagent monobenzone to dorsal skin and an in vitro HaCaT keratinocyte death model induced by monobenzone were employed to explore the effect of restraint stress, which mimics psychological stress, on depigmentation. The results indicated that restraint stress promoted vitiligo-related depigmentation, vacuolisation, spongiosis, CD8+ T lymphocyte infiltration, and loss of melanocytes in the skin. Restraint stress activated cutaneous NLR family containing pyrin domain protein 3 (NLRP3) inflammasome. In addition, restraint stress aggravated anxiety-like behaviors and increased levels of macrophage migration inhibitory factor (MIF) and corticosterone in the circulation, accompanied with decreasing the expression of cutaneous 8-oxoguanine DNA glycosylase (OGG1) in depigmentation mice. In vitro experiments demonstrated that activation of glucocorticoid receptor (GR) by cortisol upregulated NLRP3 expression dependent on MIF, and directly decreased the transcription of OGG1. Blockade of MIF reversed the NLRP3 signal in restraint stress-induced depigmentation mice. In conclusion, restraint stress promotes vitiligo-related depigmentation in mice via the activation of GR/MIF signaling pathway. The findings provide a theoretical basis for prevention and treatments of vitiligo with therapies of targeting GR, MIF, and OGG1.


Subject(s)
Hypopigmentation , Macrophage Migration-Inhibitory Factors , Vitiligo , Animals , Mice , NLR Family, Pyrin Domain-Containing 3 Protein , Receptors, Glucocorticoid , Signal Transduction , Vitiligo/chemically induced , Vitiligo/metabolism
7.
PeerJ ; 11: e15261, 2023.
Article in English | MEDLINE | ID: mdl-37151285

ABSTRACT

The status of human epidermal growth factor receptor 2 (HER2) for the prognosis in colorectal cancer (CRC) is controversial, and the characteristics of the somatic mutation spectrum, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein are unknown in HER2-amplified colorectal cancer (HACC). In order to explore these characteristics along with their correlation with clinicopathological factors and prognosis in HACC. Samples of 812 CRC patients was collected. After immunohistochemistry (IHC), 59 of 812 were found to be HER2-positive, then 26 of 59 samples were further determined to be HER2 amplification by fluorescence in situ hybridization (FISH). Somatic mutation profiling of HACC was analysed using whole exome sequencing (WES). Multiplex fluorescence immunohistochemistry (mIHC) was used for tumor-infiltrating leukocytes and tertiary lymphoid structures (TLSs), while PD-L1 protein was detected by IHC. Our results indicate that the detection rates of HER2 positivity by IHC and FISH were 7.3% and 3.2% respectively, and HER2 amplification is correlated with distant tumour metastasis. The somatic mutation profiling revealed no differences between HACC and HER2-negative CRC. However, TP 53 strongly correlated with poor prognosis in HACC. Furthermore, tumor-infiltrating T cells and TLSs in the tumor immune microenvironment, as well as PD-L1 expression, were higher in HACC than in HER2-negative controls. However, none of them were associated with the prognosis of HACC. In all, HER2 amplification is correlated with distant metastasis and TP53 gene mutation may be a potential protective mechanism of HACC.


Subject(s)
Colorectal Neoplasms , Tertiary Lymphoid Structures , Humans , B7-H1 Antigen/genetics , In Situ Hybridization, Fluorescence , Tertiary Lymphoid Structures/genetics , Colorectal Neoplasms/genetics , Mutation , Tumor Microenvironment
8.
Photodermatol Photoimmunol Photomed ; 39(5): 478-486, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37147870

ABSTRACT

PURPOSE: Ultraviolet-induced skin photoaging was involved in DNA oxidative damage. Specnuezhenide, one of the secoiridoids extracted from Ligustri Lucidi Fructus, possesses antioxidant and anti-inflammatory effects. Whether specnuezhenide ameliorates skin photoaging remains unclear. This study aimed to investigate the effect of specnuezhenide on skin photoaging induced by ultraviolet and explore the underlying mechanism. METHODS: Mice were employed to treat with ultraviolet to induce skin photoaging, then administrated 10 and 20 mg/kg of specnuezhenide. Histological analysis, protein expression, network pharmacology, and autodock analysis were conducted. RESULTS: Specnuezhenide ameliorated ultraviolet-induced skin photoaging in mice via the increase in collagen contents, and decrease in epidermal thickness, malondialdehyde content, and ß-galactosidase expression in the skin. Specnuezhenide reduced cutaneous apoptosis and inflammation in mice with skin photoaging. In addition, network pharmacology data indicated that specnuezhenide possessed potential targets on the NOD-like receptor signaling pathway. Validation experiment found that specnuezhenide inhibited the expression of NOD-like receptor family pyrin domain-containing 3, gasdermin D-C1, and Caspase 1. Furthermore, the expression of 8-Oxoguanine DNA glycosylase (OGG1), sirtuin 3 (SIRT3), and superoxide dismutase 2 was increased in specnuezhenide-treated mice with photoaging. CONCLUSION: Specnuezhenide protected against ultraviolet-induced skin photoaging in mice via a probable activation of SIRT3/OGG1 signal.


Subject(s)
Sirtuin 3 , Skin Aging , Mice , Animals , Sirtuin 3/metabolism , Sirtuin 3/pharmacology , Skin/pathology , Ultraviolet Rays/adverse effects
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(1): 274-279, 2023 Feb.
Article in Chinese | MEDLINE | ID: mdl-36765511

ABSTRACT

OBJECTIVE: To analyze the distribution and drug resistance of pathogens in oral mucositis associated with chemotherapy in hospitalized patients with malignant hematopathy, so as to provide scientific evidences for rational selection of antibiotics and infection prevention and control. METHODS: From July 2020 to June 2022, 167 patients with malignant hematopathy were treated with chemical drugs in the Department of Hematology, Hainan Hospital, and secretions from oral mucosal infected wounds were collected. VITEK2 COMPECT automatic microbial identification system (BioMerieux, France) and bacterial susceptibility card (BioMerieux) were used for bacterial identification and drug susceptibility tests. RESULTS: A total of 352 strains of pathogens were isolated from 167 patients, among which 220 strains of Gram-positive bacteria, 118 strains of Gram-negative bacteria and 14 strains of fungi, accounted for 62.50%, 33.52% and 3.98%, respectively. The Gram-positive bacteria was mainly Staphylococcus and Streptococcus, while Gram-negative bacteria was mainly Klebsiella and Proteus. The resistance of main Gram-positive bacteria to vancomycin, ciprofloxacin and gentamicin was low, and the resistance to penicillin, cefuroxime, ampicillin, cefotaxime, erythromycin and levofloxacin was high. The main Gram-negative bacteria had low resistance to gentamicin, imipenem and penicillin, but high resistance to levofloxacin, cefotaxime, cefuroxime, ampicillin and vancomycin. The clinical data of oral mucositis patients with oral ulcer (severe) and without oral ulcer (mild) were compared, and it was found that there were statistically significant differences in poor oral hygiene, diabetes, sleep duration less than 8 hours per night between two groups (P<0.05). CONCLUSION: Gram-positive bacteria is the main pathogen of oral mucositis in patients with malignant hematopathy after chemotherapy. It is sensitive to glycopeptide antibiotics and aminoglycosides antibiotics. Poor oral hygiene, diabetes and sleep duration less than 8 hours per night are risk factors for oral mucositis with oral ulcer (severe).


Subject(s)
Oral Ulcer , Stomatitis , Humans , Vancomycin/therapeutic use , Cefuroxime , Levofloxacin , Oral Ulcer/drug therapy , Drug Resistance, Bacterial , Anti-Bacterial Agents/adverse effects , Ampicillin , Penicillins , Cefotaxime , Gram-Positive Bacteria , Gram-Negative Bacteria , Gentamicins , Stomatitis/drug therapy
10.
Natl Sci Rev ; 9(8): nwab222, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36105943

ABSTRACT

Thermally activated delayed fluorescence (TADF) was achieved when electron-rich triphenylene (Tpl) donors were confined to a cage-based porous metal-organic framework (MOF) host (NKU-111) composed of electron-deficient 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (Tpt) acceptor as the ligand. The spatially separated donor and acceptor molecules in a face-to-face stacking pattern generated strong through-space charge transfer (CT) interactions with a small energy splitting between the singlet and triplet excited states (∼0.1 eV), which enabled TADF. The resulting Tpl@NKU-111 exhibited an uncommon enhanced emission intensity as the temperature increased. Extensive steady-state and time-resolved spectroscopic measurements and first-principles simulations revealed the chemical and electronic structure of this compound in both the ground and low-lying excited states. A double-channel (T1, T2) intersystem crossing mechanism with S1 was found and explained as single-directional CT from the degenerate HOMO-1/HOMO of the guest donor to the LUMO+1 of one of the nearest acceptors. The rigid skeleton of the compound and effective through-space CT enhanced the photoluminescence quantum yield (PLQY). A maximum PLQY of 57.36% was achieved by optimizing the Tpl loading ratio in the host framework. These results indicate the potential of the MOFs for the targeted construction and optimization of TADF materials.

11.
J Food Biochem ; 46(12): e14428, 2022 12.
Article in English | MEDLINE | ID: mdl-36125796

ABSTRACT

Biochanin A (Bio-A), an isoflavone abundant in chickpeas, possesses hypoglycemic, hypolipidemic, and anti-inflammatory effects. However, whether Bio-A has antihepatosteatosis effect remains unclear. This study aimed to evaluate the antihepatosteatosis effect of Bio-A on oleate (OA)-treated hepatocytes, and explore the underlying mechanism. When incubated with OA for 24 h, HepG2 cells were treated with various concentrations of Bio-A for 24 h to obtain an optimal antihepatosteatosis dose. HepG2 cells were treated with the AMP-activated protein kinase (AMPK) inhibitor Compound C, or the sirtuin-3 (SIRT3) inhibitor 3-TYP, and incubated with 50 µM Bio-A. The results indicated that 12.6% of lipid content, particularly 11.0% of triglyceride content, and the expression of adipocyte differentiation-related protein were significantly decreased in Bio-A-treated hepatosteatosis cells, followed by an increase in the expression of Beclin 1, phosphorylation of Unc-51-like kinase 1 (ULK-1), the microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I ratio, and a decrease in expression of p62. The results indicated that Bio-A upregulated autophagosome formation and autophagy flux. In addition, Bio-A increased SIRT3 expression and AMPK phosphorylation in OA-treated HepG2 cells. Blockade of AMPK and SIRT3 blocked the antihepatosteatosis effect and ULK-1 activation by Bio-A. AMPK inhibition did not eliminate the activation of SIRT3 by Bio-A. AutoDock analysis demonstrated that interaction might exist between Bio-A and SIRT3. In conclusion, Bio-A reduced fat accumulation in OA-treated HepG2 cells by activating SIRT3/AMPK/ULK-1-mediated autophagy. The findings provide a theoretical basis for the effect of Bio-A on hepatic steatosis-related diseases. PRACTICAL APPLICATIONS: This study highlights the antihepatosteatosis effects of biochanin A (Bio-A) on oleate (OA)-treated hepatocytes. Bio-A, one of the isoflavones in Cicer arietinum Linn., possesses multiple bioactivities such as antiobesity, anti-inflammation, and hypoglycemic and hypolipidemic effects. This study provides a new application of Bio-A to treat hepatic steatosis, and revealed the underlying mechanism of Bio-A involved in the activation of the SIRT3/AMPK/ULK-1-mediated autophagy. The findings provide a theoretical basis for the application of Bio-A to hepatic steatosis-related diseases.


Subject(s)
Fatty Liver , Sirtuin 3 , Humans , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/pharmacology , Hep G2 Cells , Oleic Acid/pharmacology , Signal Transduction , Sirtuin 3/genetics , Sirtuin 3/metabolism , Sirtuin 3/pharmacology
12.
Chem Biol Interact ; 364: 110051, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35872049

ABSTRACT

Formulations against liver fibrosis (LF) mitigate the progression of hepatitis to cirrhosis. However, notable toxicity of the currently available anti-LF drugs limits their long-term use. In the study, we aimed to investigate the anti-LF effects of theacrine, a purine alkaloid without obvious toxicity, on high-fat diet-, alcohol-, and carbon tetrachloride-induced LF in rats. The results indicated that 10 and 20 mg/kg of theacrine ameliorated hepatic fibrosis, steatosis, and inflammation in LF rats. Mechanistically, theacrine reduced hepatic stellate cell (HSC)-related α-smooth muscle actin expression, and decreased cholesterol accumulation, followed by decreased expression of transforming growth factor-ß1, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α. In addition, theacrine upregulated the phosphorylation of AMP-activated protein kinase, accompanied by decreased expression of ß-catenin and stearoyl-CoA desaturase 1, and increased the expression of sirtuin 3 (SIRT3). Further investigation revealed that the theacrine-mediated decrease in cholesterol was independent of cholesterol synthesis or low-density lipoprotein (LDL) uptake in hyperlipidemia mice. However, theacrine activated farnesoid X receptor (FXR), a ß-catenin conjugated protein, accompanied with decreased expression of cholesterol 7α-hydroxylase and sterol 12α-hydroxylase. In conclusion, theacrine alleviated experimental LF in rats by lowering cholesterol storage and decreasing cholesterol-related HSC activation. A plausible mechanism of theacrine on cholesterol metabolism may involve activation of SIRT3-FXR signaling pathway followed by decreased intestinal cholesterol absorption.


Subject(s)
Sirtuin 3 , Animals , Cholesterol/metabolism , Liver , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Mice , Rats , Signal Transduction , Sirtuin 3/metabolism , Uric Acid/analogs & derivatives , beta Catenin/metabolism
13.
World J Clin Cases ; 10(10): 3088-3100, 2022 Apr 06.
Article in English | MEDLINE | ID: mdl-35647131

ABSTRACT

BACKGROUND: Pleural effusions occur for various reasons, and their diagnosis remains challenging despite the availability of different diagnostic modalities. Medical thoracoscopy (MT) can be used for both diagnostic and therapeutic purposes, especially in patients with undiagnosed pleural effusion. AIM: To assess the diagnostic efficacy and safety of MT in patients with pleural effusion of different causes. METHODS: Between January 1, 2012 and April 30, 2021, patients with pleural effusion underwent MT in the Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Shaanxi, China). According to the discharge diagnosis, patients were divided into malignant pleural effusion (MPE), tuberculous pleural effusion (TBPE), and inflammatory pleural effusion (IPE) groups. General information, and tuberculosis- and effusion-related indices of the three groups were analyzed. The diagnostic yield, diagnostic accuracy, performance under thoracoscopy, and complications of patients were compared among the three groups. Then, the significant predictive factors for diagnosis between the MPE and TBPE groups were analyzed. RESULTS: Of the 106 patients enrolled in this 10-year study, 67 were male and 39 female, with mean age of 57.1 ± 14.184 years. Among the 74 thoracoscopy-confirmed patients, 41 (38.7%) had MPE, 21 had (19.8%) TBPE, and 32 (30.2%) were undiagnosed. Overall diagnostic yield of MT was 69.8% (MPE: 75.9%, TBPE: 48.8%, and IPE: 75.0%, with diagnostic accuracies of 100%, 87.5%, and 75.0%, respectively). Under thoracoscopy, single or multiple pleural nodules were observed in 81.1% and pleural adhesions in 34.0% with pleural effusions. The most common complication was chest pain (41.5%), followed by chest tightness (11.3%) and fever (10.4%). Multivariate logistic regression analyses showed effusion appearance [odds ratio (OR): 0.001, 95%CI: 0.000-0.204; P = 0.010] and carcinoembryonic antigen (OR: 0.243, 95%CI: 0.081-0.728; P = 0.011) as significant for differentiating MPE and TBPE, with area under the receiver operating characteristic curve of 0.977 (95%CI: 0.953-1.000; P < 0.001). CONCLUSION: MT is an effective, safe, and minimally invasive procedure with high diagnostic yield for pleural effusion of different causes.

14.
Eur J Surg Oncol ; 48(1): 211-217, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34483031

ABSTRACT

BACKGROUND: Microsatellite instability, programmed death-ligand 1 and tumor-infiltrating leukocytes are prognostic biomarkers in colorectal cancer but unknown toward familial adenomatous polyposis. AIM: To investigate the prognostic and clinicopathological roles of microsatellite instability, programmed death-ligand 1 and tumor-infiltrating leukocytes in familial adenomatous polyposis. METHODS: Clinical data and paraffin embedded tissues from 45 familial adenomatous polyposis patients were collected. Microsatellite instability was detected by immunohistochemistry and polymerase chain reaction. Programmed death-ligand 1 was detected by immunohistochemistry. Tumor-infiltrating leukocytes comprising CD8+ T cells, M1 and M2 tumor associated macrophages, CD56bright and CD56dim natural killer cells were analyzed using multiple fluorescence immunohistochemistry. RESULTS: Microsatellite instability high was noted in 6 samples but not associated with overall survival or progression-free survival. Programmed death-ligand 1 is negative on tumor cells but positive on tumor-infiltrating leukocytes, and positive programmed death-ligand 1 expression on tumor-infiltrating leucocytes is associated with overall survival. Low CD56bright natural killer cell infiltration was associated with longer progression-free survival and was an independent prognostic factor in FAP. CONCLUSION: For familial adenomatous polyposis, microsatellite instability high can be found but has no correlation with prognosis; programmed death-ligand 1 on tumor-infiltrating leukocytes is related with overall survival; CD56bright natural killer cell is an independent prognostic factor associating with longer progression-free survival.


Subject(s)
Adenocarcinoma/genetics , Adenomatous Polyposis Coli/genetics , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes/metabolism , Killer Cells, Natural/metabolism , Lymphocytes, Tumor-Infiltrating/metabolism , Microsatellite Instability , Tumor-Associated Macrophages/metabolism , Adenocarcinoma/immunology , Adenocarcinoma/metabolism , Adenomatous Polyposis Coli/immunology , Adenomatous Polyposis Coli/metabolism , Adult , Aged , CD56 Antigen/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/immunology , Colorectal Neoplasms/metabolism , Female , Humans , Male , Middle Aged , Prognosis , Progression-Free Survival , Young Adult
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 306-310, 2021 Feb.
Article in Chinese | MEDLINE | ID: mdl-33554840

ABSTRACT

In recent years, it is found that the classical IKKα and IKKß pathway were closely relates with hematological tumors, except the classical pathogenesis, moreover the classical IKKß pathway is deeply studied. The studies indicated that the IKKßis activated to phosphorylate the NF-κB through multiple cascades under the effect of extracellular IL-6, TNF-α and other stimulating factors. At the cellular level, the classical IKKßcan promote the tumor cell survival and proliferation, reduce the cell apoptosis, and promote the angiogenesis and cell transfer. Although the classical IKKα plays a role in regulating IKKß activity, but its role in non-classical pathway is more prominent. This review briefly summarizes the latest advance of researches on the pathogenesis of hematological malignancies in term of IKKα and IKKßpathway, so as to provide the theoretic basis for deeply understanding and studying the pathogenesis of hematologic tumors. At present, blocking the classical IKKα and IKKß pathway has become a new target for treatment of hematological tumors, moreover, some specific inhibitor for IKKα and IKKßpathway have been developed, for example, LY2409881, BMS 345541 and so on. Most of these drugs are in clinical trials and display some good anti-tumor effects.


Subject(s)
Hematologic Neoplasms , Signal Transduction , Cell Survival , Humans , I-kappa B Kinase/metabolism , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha
16.
PLoS One ; 15(6): e0234261, 2020.
Article in English | MEDLINE | ID: mdl-32516318

ABSTRACT

The aims of this study were to investigate the prevalence and proportion of laboratory-confirmed urethral Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections that were asymptomatic among individuals presenting to clinics in Shenzhen and the risk factors related to asymptomatic CT infection. In a cross-sectional study, eligible individuals were invited to participate in the questionnaire, and urine specimens were collected to identify CT and NG infections using a nucleic acid amplification test (NAAT). Considering the differences in the presentation of symptoms between men and women, this study was stratified by gender. Corresponding outcomes were analyzed by Chi-square test and multivariate logistic regression. A total of 2,871 participants were asymptomatic and included in our analyses: 1120 (39.0%) men and 1751 (61.0%) women. The prevalence of asymptomatic NG and CT infections was 0.9% and 6.2% in men, and 0.4% and 7.9% in women, respectively. The proportion of asymptomatic urethral CT among men with urethral CT was 28.3%; for women, it was 34.2%. For asymptomatic men with CT, 3 independent risk factors were identified: (1) men under the age of 30 (aOR, 1.83; 95% CI, 1.11-3.03); (2) being employed in the commercial service work (2.82; 1.36-5.84); and (3) being recruited through the urological department (2.12; 1.19-3.79). For asymptomatic women with urethral CT, age less than 30 years was a risk factor. In conclusion, a substantial prevalence of asymptomatic CT infections was found among men and women presenting to clinics in Shenzhen. The significant correlation between asymptomatic CT infection and these risk factors could help identify high-risk populations and guide screening.


Subject(s)
Ambulatory Care Facilities/statistics & numerical data , Asymptomatic Infections/epidemiology , Chlamydia Infections/epidemiology , Chlamydia trachomatis/physiology , Gonorrhea/epidemiology , Neisseria gonorrhoeae/physiology , Adult , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Risk Factors , Sex Distribution
17.
Inorg Chem ; 59(13): 9005-9013, 2020 Jul 06.
Article in English | MEDLINE | ID: mdl-32526144

ABSTRACT

In spite of the attractive potential application of the dynamic behavior and defect of metal-organic framework (MOF), the achievement of these features is a challenging goal in the MOF research field. Herein, we report a Co(II) MOF, namely, [Co3(L)2(4-PTZ)2(H2O)2]n·solvent (H2L = 5-(isonicotinamido)isophthalic acid, 4-PTZ = 5-(4-pyridyl)-1H-tetrazole), that features dynamic structural transformation behaviors. By varying the coordination configuration of metal center through the removal of coordinated water molecules, the porous compound could undergo structural transformation to give a new crystalline phase with larger pore dimension. Moreover, the new phase features a mesoporous structure originating from the spatial defect that formed with the transformation process, which indicates that the modulation of dynamic behavior of the MOF could be a potential method for the engineering of a spatial defect. In addition, the gas sorption investigation results reveal that the new phase has enhanced selectivity for CO2/N2, CO2/CH4, and C2H2/C2H4 systems compared with that of the pristine phase, suggesting the potential of spatial defect engineering for the tuning of MOF gas sorption properties.

18.
Zhen Ci Yan Jiu ; 44(12): 906-10, 2019 Dec 25.
Article in Chinese | MEDLINE | ID: mdl-31867911

ABSTRACT

OBJECTIVE: To observe the effect of acupoint application at bilateral "Tianshu" (ST25) on intestinal mobility and immunoactivity of vasoactive intestinal peptide (VIP) and substance P (SP) in colonic myenteric plexus of rats with functional constipation (FC), so as to analyze its mechanisms underlying improving FC. METHODS: Forty male SD rats were randomly divided into 4 groups, namely normal control, model, acupoint application and medication, with 10 rats in each group. The FC model was established by gavage of Loperamide Hydrochloride suspension fluid (0.5 mg/mL, 3 mg·kg-1·d-1) for 7 days. Herbal medicine paste (composed of Rheum Officinale, Sodium Sulfate, Mangnolia Officinalis, etc.) was applied to bilateral ST25 for 6 h, once daily for 4 weeks. Rats of the medication group were treated by gavage of Mosapride suspension fluid (0.15 mg/mL, 1.58 mg·kg-1·d-1) for 4 weeks. After the treatment, the rats were deprived of water for 12 hours, and then treated by gavage of 2 mL of activated carbon suspension, followed by recording the first black defecation time and the number of fecal particles and water content of feces within 6 h so as to assess the intestinal mobility. The immunoactivity and average surface density of VIP and SP positive granules in the colonic myenteric plexus were detected by immunohistochemistry. RESULTS: Compared with the normal control group, the first black defecation time was significantly prolonged, and the number and water content of fecal particles within 6 h, and the expression and the average surface density of VIP and SP were significantly reduced in the model group (P<0.01). After the treatment and compared with the model group, the first black defecation time was shortened, and the fecal water content and fecal particle number within 6 h, as well as the expression and the average surface density of VIP and SP were considerably increased in both acupoint application and medication groups (P<0.01). There were no significant differences between the acupoint application and medication groups in all the indexes mentioned above after the interventions (P>0.05). CONCLUSION: Acupoint application may improve the intestinal motility in FC rats, which may be asso-ciated with its effects in up-regulating the immunoactivity of VIP and SP in colonic myenteric plexus of the large intestine.


Subject(s)
Myenteric Plexus , Vasoactive Intestinal Peptide , Acupuncture Points , Animals , Constipation , Herbal Medicine , Male , Rats , Rats, Sprague-Dawley , Substance P
19.
Math Biosci Eng ; 16(5): 5947-5971, 2019 06 27.
Article in English | MEDLINE | ID: mdl-31499747

ABSTRACT

Osteoporosis is the most common bone metabolic disease. Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Recent researches have greatly broaden our understanding of molecular mechanisms of osteoporosis. However, the molecular mechanisms of key mRNAs and lncRNAs, and their interactions leading to osteoporosis are still not entirely clear. The purpose of this work is to study the key mRNAs and lncRNAs, and their interactions involved in bone mineral homeostasis and osteoclastogenesis. Systematic analyses such as differential expression analysis, GO and KEGG analysis, and PPI network construction revealed that up-regulated mRNAs were significantly enriched in inflammation-related pathways. Moreover, we observed that the down-regulated proteins, including JDP2, HADC4, HDAC5, CDYL2, ACADVL, ACSL1 and BRD4, were key components in the down-regulated PPI network, indicating that the downregulation of histone deacetylases and cofactors, such as, HDAC4, HDAC5 and JDP2 may be critical regulators in osteoclastogenesis. In addition, we also highlighted one lncRNA, RP11-498C9.17, was highly correlated with epigenetic regulators, such as HDAC4, MORF4L1, HMGA1 and DND1, indicating that the lncRNA RP11-498C9.17 may also be an epigenetic regulator. In conclusion, our integrative analysis reveals key mRNAs and lncRNAs, involved in bone mineral homeostasis and osteoclastogenesis, which not only broaden our insights into lncRNAs in bone mineral homeostasis and osteoclastogenesis, but also improve our understanding of molecular mechanism.


Subject(s)
Epigenesis, Genetic , Gene Expression Regulation , Monocytes/metabolism , Osteoporosis/metabolism , RNA, Long Noncoding/metabolism , RNA, Messenger/metabolism , Autophagy , Bone Remodeling , Gene Expression Profiling , Homeostasis , Humans , Inflammation , Osteoblasts/metabolism , Osteoclasts/metabolism , Protein Interaction Mapping , Signal Transduction , Up-Regulation
20.
Angew Chem Int Ed Engl ; 58(39): 13890-13896, 2019 Sep 23.
Article in English | MEDLINE | ID: mdl-31231920

ABSTRACT

Photonic materials use photons as information carriers and offer the potential for unprecedented applications in optical and optoelectronic devices. In this study, we introduce a new strategy for photonic materials using metal-organic frameworks (MOFs) as the host for the rational construction of donor-acceptor (D-A) heterostructure crystals. We have engineered a rich library of heterostructure crystals using the MOF NKU-111 as a host. NKU-111 is based upon an electron-deficient tridentate ligand (acceptor) that can bind to various electron-rich guests (donors). The resulting heterocrystals exhibit spatially segregated multi-color emission resulting from the guest-dependent charge-transfer (CT) emission. Spatially effective mono-directional energy transfer results from tuning the energy gradient between adjacent domains through the selection of donor guest molecules, which suggests potential applications in integrated optical circuit devices, for example, photonic diodes, on-chip signal processing, optical logic gates.

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