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1.
Neuroimmunomodulation ; : 1-9, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32062665

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is a complex demyelinating disease involving central nervous system (CNS). It is still a challenge to secure an effective therapeutic strategy against this disease. Carbenoxolone (CBX) is a derivative of glycyrrhetinic acid, which is widely used in brain research for its gap-junction inhibition effects. Many researchers have observed CBX-mediated suppression of CNS inflammation in their studies. OBJECTIVE: We want to further examine its anti-inflammation effects in CNS demyelinating disease like MS. METHODS: Thus, our study applied an experimental autoimmune encephalomyelitis (EAE) mouse model and examined the effects of CBX on it. RESULTS AND CONCLUSIONS: We found that CBX significantly reversed the EAE severity and pathology in EAE. IL-17-secreting and IFN-γ-secreting CD4+ T lymphocytes were remarkably lower in the spleen of CBX-treated mice. Production of IL-23 and IL-17 from cortex in EAE animals was markedly reduced by CBX. Furthermore, CBX treatment increased the expression of brain-derived neurotrophic factor. This study provides evidence for the protective role of CBX against EAE.

2.
Thorac Cancer ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017466

RESUMO

Immune checkpoint inhibitors (ICIs) are able to reactivate the immune system, thereby enhancing the anti-tumor effects. However, over-activated T cells may induce immune-related adverse events (irAEs). Hematological irAEs are rarely reported which mainly represent monolineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even life-threatening diseases such as hemophagocytic lymphohistiocytosis. Here, the clinical manifestations of hematological irAEs are summarized and recommendations for diagnosis and treatment proposed. KEY POINTS: Significant findings of the study • Hematological immune-related adverse events (irAEs) caused by checkpoint inhibitors are rare and may sometimes be life-threatening. This study summarizes the manifestations of hematological irAEs and proposes preliminary recommendations for diagnosis and treatment. What this study adds • Much still remains unknown regarding hematological irAEs caused by checkpoint inhibitors. This study delineates the overview of hematological irAEs, and provides practical treatment suggestions, in particular addressing the issue of rechallenge.

3.
Reprod Sci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046379

RESUMO

Obesity is closely related to reproductive disorders, which may eventually lead to infertility in both males and females. Ovarian granulosa cells play a critical role during the maintenance of oocyte development through the generation of sex steroids (mainly estradiol and progesterone) and different kinds of growth factors. However, the molecular mechanism of obesity-induced granulosa cell dysfunction remains poorly investigated. In our current study, we observed that high-fat diet feeding significantly increased the level of glucose-regulated protein 78 kDa (GRP78) protein expression in mouse granulosa cells; testosterone-induced estradiol generation was impaired accordingly. To further evaluate the precise mechanism of lipotoxicity-induced granulosa cell dysfunction, mouse primary granulosa cells were treated with palmitate, and the expression levels of ER stress markers were evaluated by real-time PCR and western blot. Lipotoxicity significantly increased ER stress but impaired the mRNA expression of granulosa cell function-related makers, including androgen receptor (Ar), cytochrome P450 family 19 subfamily A member 1 (Cyp19a1), hydroxysteroid 17-beta dehydrogenase 1 (Hsd17b1), and insulin receptor substrate 1 (Irs1). Impaired testosterone-induced estradiol generation was also observed in cultured mouse granulosa cells after palmitate treatment. Insulin augmented testosterone induced estradiol generation through activation of the AKT pathway. However, palmitate treatment abolished insulin-promoted aromatase expression and estradiol generation by the stimulation of ER stress. Overexpression of IRS1 significantly ameliorated palmitate- or tunicamycin-induced impairment of aromatase expression and estradiol generation. Taken together, our current study demonstrated that lipotoxicity impaired insulin-stimulated estradiol generation through activated ER stress and inhibited IRS1 pathway.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(2): 106-111, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32051075

RESUMO

OBJECTIVE: To study the clinical features of influenza with plastic bronchitis (PB) in children, and to improve the awareness of the diagnosis and treatment of PB caused by influenza virus. METHODS: A retrospective analysis was performed for the clinical data of 70 children with lower respiratory influenza virus infection from October 2018 to October 2019. According to the presence or absence of PB, they were divided into an influenza+PB group with 12 children and a non-PB influenza group with 58 children. Related clinical data were collected for the retrospective analysis, including general information, clinical manifestations, laboratory examination, imaging findings, treatment, and prognosis. RESULTS: In the influenza+PB group, most children experienced disease onset at the age of 1-5 years, with the peak months of January, February, July, and September. Major clinical manifestations in the influenza+PB group included fever, cough, and shortness of breath. The influenza+PB group had significantly higher incidence rates of shortness of breath and allergic diseases such as asthma than the non-PB influenza group (P<0.05). Of the 12 children in the influenza+PB group, 7(58%) had influenza A virus infection and 5 (42%) had influenza B virus infection, among whom 1 had nephrotic syndrome. For the children in the influenza+PB group, major imaging findings included pulmonary consolidation with atelectasis, high-density infiltration, pleural effusion, and mediastinal emphysema. Compared with the non-PB influenza group, the influenza+PB group had a significantly higher proportion of children who were admitted to the pediatric intensive care unit (P<0.05). Bronchoscopic lavage was performed within 1 week after admission, and all children were improved and discharged after anti-infective therapy and symptomatic/supportive treatment. CONCLUSIONS: Influenza with PB tends to have acute onset and rapid progression, and it is important to perform bronchoscopy as early as possible. The possibility of PB should be considered when the presence of shortness of breath, allergic diseases such as asthma or nephrotic syndrome in children with influenza.

5.
DNA Cell Biol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999483

RESUMO

Clear cell renal cell carcinoma is the most common in all of the renal cancers; however, it lacks ideal molecular target for treatment. In the present study, we identified that ufmylation, a novel ubiquitin-like modification, was significantly upregulated in renal cancer tissues. Ufmylation is known to be closely associated with endoplasmic reticulum (ER) stress and protein quality control. To explore the relation between ufmylation and protein degradation pathways in renal cancer cells, we pharmacologically altered the ubiquitin-proteasome (UPS) and autophagy pathways. We found that the ufmylation levels were not varied by autophagy activation or inhibition. Consistently, the LC3 conversion, as an important biomarker of autophagy, was comparable between renal caner tissues and para-cancer tissues, indicating that the increase of ufmylation in renal cancer may be not related with autophagy. In contrast, blocking UPS with MG132 activated ufmylation in renal cancer cells, suggesting that the activation of ufmylation in renal cancer may be associated with the UPS activity. However, the ufmylation levels were not associated with mutations of the von Hippel-Lindau (VHL) gene, a specific E3 ligase of the UPS and has high mutation rate in renal cancer. Besides, we found that sunitinib, a multi-targeted tyrosine kinase inhibitor, could significantly inhibit ufmylation, whereas overexpression of active Ufm1 partially inhibited the antitumor effects of sunitinib. These results highlight that ufmylation might be a novel molecular candidate for renal cancer.

6.
Water Res ; 172: 115504, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31981901

RESUMO

Activation of persulfates (i.e., peroxydisulfate (PDS) and peroxymonosulfate (PMS)) by nanoscale zero-valent iron (nZVI) is reported to be effective in oxidative treatment of environmental contaminants. It has been widely accepted in numerous literature that sulfate radical (SO4•-) formed from the decomposition of persulfates activated by aqueous Fe(II) released from nZVI corrosion is responsible for the oxidative performance in nZVI/persulfates systems. In this work, by employing methyl phenyl sulfoxide (PMSO) as a probe, we demonstrated that the activation of persulfates by nZVI through electron transfer led to SO4•- formation, while the homogeneous activation of persulfate by the released Fe(II) resulted in ferryl ion species (Fe(IV)) generation in nZVI/persulfates systems. Similarly, nanoscale zero-valent aluminum (nZVAl) and zinc (nZVZn) were also demonstrated to be able to donate electron to persulfates leading to SO4•- formation. However, the insulative aluminum oxide shell hindered the electron transfer leading to the poor persulfates decomposition, while the conductive iron and zinc oxide shell enabled the electron transfer process resulting in a continuous generation of SO4•-. Further, it was obtained that the relative contribution of SO4•- and Fe(IV) in nZVI/persulfates systems was independent of the initial concentration of nZVI and PDS, but was positively correlated with PMS concentration. In addition, the increase of pH from 3 to 7 led to the decrease of the relative contribution of Fe(IV), which was rationalized by the decrease of availability of aqueous Fe(II) at higher pH. Our findings not only shed lights on the nature of the reactive intermediate formed in the nZVI/persulfates systems, but also unprecedentedly distinguished the surface activation of persulfates from the homogeneous catalysis process.

7.
Transl Stroke Res ; 11(1): 108-121, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30847778

RESUMO

Neutrophils are forerunners to brain lesions after ischemic stroke and exert elaborate functions. However, temporal alterations of cell count, polarity, extracellular trap formation, and clearance of neutrophils remain poorly understood. The current study was aimed at providing basic information of neutrophil function throughout a time course following stroke onset in patients and animal subjects. We found that neutrophil constitution in peripheral blood increased soon after stroke onset of patients, and higher neutrophil count indicated detrimental stroke outcomes. Comparably, neutrophil count in peripheral blood of stroke mice peaked at 12 h after cerebral ischemia, followed by a 1-2-day spike in brain lesions. In stroke lesion, clearance of neutrophils peaked at 2 days after stroke and extracellular traps were mostly detected at 2-3 days after stroke. In neutrophil infiltrated into stroke lesion, expression of the N2 marker CD206 was relatively stable. We found that the N2 phenotype facilitated neutrophil clearance by macrophage and did not further induce neuronal death after ischemic injury compared with N0 or N1 neutrophils. Skewing neutrophil toward the N2 phenotype before stroke reduced infarct volumes at 1 day after tMCAO. Conditioned medium of ischemic neurons drove neutrophils away from the protective N2 phenotype and increased the formation of extracellular traps. Conclusively, neutrophil function has an important impact on stroke outcomes. Neutrophil frequency in the peripheral blood could be an early indicator of stroke outcomes. N2 neutrophils facilitate macrophage phagocytosis and are less harmful to ischemic neurons. Directing neutrophils toward the N2 phenotype could be a promising therapeutic approach for ischemic stroke.

8.
J Cell Mol Med ; 24(1): 605-617, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657881

RESUMO

The transition from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is detrimental to bladder cancer (BLCA) patients. Here, we aimed to study the underlying mechanism of the subtype transition. Gene set variation analysis (GSVA) revealed the epithelial-mesenchymal transition (EMT) signalling pathway with the most positive correlation in this transition. Then, we built a LASSO Cox regression model of an EMT-related gene signature in BLCA. The patients with high risk scores had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low risk scores. The EMT-related gene signature also performed favourably in the accuracy of prognosis and in the subtype survival analysis. Univariate and multivariate Cox regression analyses demonstrated that the EMT-related gene signature, pathological N stage and age were independent prognostic factors for predicting survival in BLCA patients. Furthermore, the predictive nomogram model was able to effectively predict the outcome of BLCA patients by appropriately stratifying the risk score. In conclusion, we developed a novel EMT-related gene signature that has tumour-promoting effects, acts as a negative independent prognostic factor and might facilitate personalized counselling and treatment in BLCA.

9.
Oncogene ; 39(2): 428-442, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31485019

RESUMO

Exosomes are emerging as important elements that participate in intercellular communication and tumor microenvironment modulation, but the exact mechanisms by which tumor exosomes facilitate the generation of the immunosuppressive microenvironment remain unclear. Here we investigated the effects of glioma-derived exosomes (GDEs) on macrophage polarization and glioma progression. We also performed microRNA sequencing analysis of GDEs to identify the microRNA that mediated macrophage polarization. The microRNA-associated intracellular signaling pathway in macrophages was further investigated. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly induced M2 macrophage polarization, which subsequently promoted glioma proliferation, migration and invasion in vitro and in vivo. MicroRNA sequencing analysis identified miR-1246 as the most enriched microRNA in H-GDEs. Moreover, miR-1246 was enriched in the CSF of GBM patients and decreased after tumor resection. Further investigation determined that miR-1246 mediated H-GDE-induced M2 macrophage polarization by targeting TERF2IP to activate the STAT3 signaling pathway and inhibit the NF-κB signaling pathway. Our study elucidated a mechanism by which hypoxia and glioma influence M2 macrophage polarization via exosomes, which could facilitate the formation of the immunosuppressive microenvironment. Moreover, our results suggested that miR-1246 in the CSF of GBM patients may be a novel biomarker for GBM diagnosis and that treatment targeting microRNA-1246 may contribute to antitumor immunotherapy.

10.
J Sci Food Agric ; 100(1): 92-101, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31435952

RESUMO

BACKGROUND: Oyster polypeptides have various biofunctions, such as anti-cancer and anti-oxidative stress, but whether it has the protective effects to primary ovarian failure (POF) remains poorly understand. To address this issue, daily gavage of oyster polypeptides was performed to investigate their protective effect, basing on d-galactose-induced POF model in C57BL/6 female mice. RESULTS: Oyster polypeptides restored the irregular estrous cycles and the abnormal serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone (P) levels as well as the decreased mRNA expression level of Amh that were induced by d-galactose. The follicle development of POF mice was improved by increasing the primordial follicle ratio and decreasing the atretic follicle number after oral administration of oyster polypeptides. Moreover, in the oyster polypeptides treated mice, the total superoxide dismutase (T-SOD) activity was significantly increased, while the malondialdehyde levels were significantly decreased. The mRNA expression levels of stress-related genes (SOD2, SIRT1 and FOXO3a) were remarkably up-regulated after d-galactose induction, but the up-regulation was weakened or disappeared by the gavage of oyster polypeptides. In addition, oyster polypeptides treatment also reduced the apoptosis of the ovarian granulosa cells and down-regulated the mRNA expression levels of apoptosis-related genes (p53 and Bad but not Bcl-2). CONCLUSION: This study reveals that oyster polypeptides may protect ovary against d-galactose-induced POF by their anti-oxidative stress activity to rescue d-galactose-induced ovarian oxidative damage and therefore to prevent ovarian cells apoptosis, thereby tipping the abnormality trigged by POF to get close to the normal levels. © 2019 Society of Chemical Industry.


Assuntos
Ostreidae/química , Peptídeos/administração & dosagem , Insuficiência Ovariana Primária/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Feminino , Galactose/efeitos adversos , Humanos , Hormônio Luteinizante/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/metabolismo , Progesterona/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
11.
Mol Oncol ; 14(2): 407-425, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31856384

RESUMO

Gliomas are the most common primary malignant tumours of the central nervous system, and new molecular biomarkers are urgently needed for diagnosis and targeted therapy. Here, we report that increased beta-site APP-cleaving enzyme 2 (BACE2) expression is associated with increases in the grade of human glioma, the incidence of the mesenchymal molecular glioblastoma multiforme subtype and the likelihood of poor prognoses for patients. BACE2 knockdown suppressed cell invasion, cell migration and tumour growth both in vitro and in vivo, while BACE2 overexpression promoted the mesenchymal transition and cell proliferation. Furthermore, TGFß1 stimulated BACE2 expression through Smad-dependent signalling, which modulated TNF-α-induced NF-κB activity through the PP1A/IKK pathway to promote tumorigenesis in both U87MG and U251 cells. Our study indicated that BACE2 plays a significant role in glioma development. Therefore, BACE2 is a potential therapeutic target for human gliomas due to its function and ability to be regulated.

13.
Mult Scler Relat Disord ; 39: 101888, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31869599

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and MS are the most common autoimmune inflammatory demyelinating diseases of the CNS. However, the mechanisms of pathogenesis are still unclear. nucleotide-binding leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3), an important protein of the innate immune system that is activated by mitochondrial DNA (mtDNA), has been reported to be associated with various autoimmune disorders. OBJECTIVE: To assess the levels of cerebrospinal fluid (CSF) NLRP3, mtDNA and inflammation-associated cytokines (IL-1ß, IL-6 and IL-17) in patients with NMOSD and MS, and to examine the correlations between these factors. METHODS: 28 NMOSD patients, 15 MS patients, and 16 controls with non-inflammatory neurological diseases were recruited. NLRP3 inflammasome, IL-1ß, IL-6 and IL-17 were measured by ELISA. CSF extracellular mtDNA was measured by qPCR. The severity of clinical presentation was evaluated by EDSS score. RESULTS: CSF levels of NLRP3, mtDNA, IL-1ß, IL-6 and IL-17 were higher in NMOSD patients than in controls. Elevated CSF NLRP3, mtDNA and IL-6 were found in MS patients compared with controls. CSF NLRP3 and IL-6 levels were significantly higher in NMOSD patients than in MS patients. The EDSS scores of NMOSD patients during relapse were positively correlated with CSF NLRP3 and mtDNA. CONCLUSION: Our findings suggest that CSF levels of the NLRP3 inflammasome may serve as a diagnostic biomarker for distinguishing NMOSD and MS. Pyroptosis mediated by the NLRP3 inflammasome following mitochondrial damage may play an important role in the pathogenesis of these neuroinflammatory disorders, especially NMOSD.

14.
J Neuroinflammation ; 16(1): 242, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779652

RESUMO

BACKGROUND: Preserving the integrity of the blood-brain barrier (BBB) is beneficial to avoid further brain damage after acute ischemic stroke (AIS). Astrocytes, an important component of the BBB, promote BBB breakdown in subjects with AIS by secreting inflammatory factors. The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) protects the BBB and reduces brain inflammation from cerebral ischemia, and GLP-1R is expressed on astrocytes. However, the effect of Ex-4 on astrocytes in subjects with AIS remains unclear. METHODS: In the present study, we investigated the effect of Ex-4 on astrocytes cultured under oxygen-glucose deprivation (OGD) plus reoxygenation conditions and determined whether the effect influences bEnd.3 cells. We used various methods, including permeability assays, western blotting, immunofluorescence staining, and gelatin zymography, in vitro and in vivo. RESULTS: Ex-4 reduced OGD-induced astrocyte-derived vascular endothelial growth factor (VEGF-A), matrix metalloproteinase-9 (MMP-9), chemokine monocyte chemoattractant protein-1 (MCP-1), and chemokine C-X-C motif ligand 1 (CXCL-1). The reduction in astrocyte-derived VEGF-A and MMP-9 was related to the increased expression of tight junction proteins (TJPs) in bEnd.3 cells. Ex-4 improved neurologic deficit scores, reduced the infarct area, and ameliorated BBB breakdown as well as decreased astrocyte-derived VEGF-A, MMP-9, CXCL-1, and MCP-1 levels in ischemic brain tissues from rats subjected to middle cerebral artery occlusion. Ex-4 reduced the activation of the JAK2/STAT3 signaling pathway in astrocytes following OGD. CONCLUSION: Based on these findings, ischemia-induced inflammation and BBB breakdown can be improved by Ex-4 through an astrocyte-dependent manner.

15.
Biomed Res Int ; 2019: 1950790, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781595

RESUMO

The present study aimed at investigating the influence of norspermidine on the formation of dual-species biofilms composed of Streptococcus mutans (S. mutans) and Streptococcus sanguinis (S. sanguinis). Crystal violet assay was conducted to assess the formation of single-species biofilms of S. mutans and S. sanguinis, and the growth curve was carefully observed to monitor the growth of these two species of bacteria. Fluorescence in situ hybridization (FISH) and MTT array were used to analyze the composition and metabolic activity of the dual-species biofilms, respectively. Extracellular polysaccharides (EPS)/bacteria staining, anthrone method, and scanning electron microscopy (SEM) imaging were conducted to study the synthesis of EPS by dual-species biofilms. Lactic acid assay and pH were measured to detect dual-species biofilm acid production. We found that norspermidine had different effects on S. mutans and S. sanguinis including their growth and biofilm formation. Norspermidine regulated the composition of the dual-species biofilms, decreased the ratio of S. mutans in dual-species biofilms, and reduced the metabolic activity, EPS synthesis, and acid production of dual-species biofilms. Norspermidine regulated dual-species biofilms in an ecological way, suggesting that it may be a potent reagent for controlling dental biofilms and managing dental caries.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31772596

RESUMO

Spleen-deficiency syndrome and damp-heat syndrome are the two most common syndromes of vaginitis in traditional Chinese medicine (TCM). Although it is known that the vaginal microbiota is closely associated with vaginitis, present studies have not fully elucidated the relationship between the composition of the vaginal microbiome and type of TCM syndrome because of the limitations in the present reductionist approaches. Samples of vaginal secretions were collected from patients with bacterial vaginitis and healthy subjects with spleen-deficiency syndrome and damp-heat syndrome, in order to analyze the constitution of the vaginal microflora using 16S rRNA sequencing methods that encompass taxonomic units, alpha diversity rarefaction curves, and principal component analyses. This prospective study indicated that there was a statistically significant difference in the composition of the vaginal microbiome between patients with spleen-deficiency syndrome and patients with damp-heat syndrome. Streptococcus was the dominant microbiota in patients with spleen-deficiency syndrome. This can serve as a biomarker for differentiating spleen-deficiency syndrome and damp-heat syndrome. In addition, as indicated by the findings on the samples, patients with bacterial vaginitis of dominant abundance in Pseudomonadaceae might be prone to manifest spleen-deficiency syndrome, while patients with bacterial vaginitis of dominant abundance in Prevotella might be prone to manifest damp-heat syndrome. These present findings can provide a new approach to acquire a scientific understanding of the syndromes of TCM, which in turn would benefit the development of personalized medicine, in terms of ancient medicine and complex biological systems.

17.
J Asian Nat Prod Res ; : 1-8, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755312

RESUMO

A new series of C-3'-N-sulfonyl paclitaxel analogs were designed and synthesized from 1-deoxybaccatin VI and their structures were confirmed by 1H NMR, 13C NMR and high resolution MS. The synthesized compounds were evaluated for their in vitro anti-Hepatocellular carcinoma (HCC) activity against human hepatoma (HepG2) cell line. Bioassay results showed that compounds 17c, 17d and 17f exhibited more potent inhibitory activity against HepG2 cell line in comparison with paclitaxel. It is suggested that paclitaxel analogs containing the C-3'-N-sulfonyl could be considered as a precursor structure for further synthesis of more potent analogues.

18.
Nanomedicine ; 24: 102118, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678180

RESUMO

The benefit of chemotherapy as a constituent of transcatheter arterial chemoembolization (TACE) is still in debate. Recently we have developed arsenic trioxide nanoparticle prodrug (ATONP) as a new anticancer drug, but its systemic toxicity is a big issue. In this preclinical TACE study, ATONP emulsified in lipiodol behaved as drug-eluting bead manner. Sustained release of arsenic from ATONP within occluded tumor caused very low arsenic level in plasma, avoiding the "rushing out" effect as ATO did. Correspondingly, intratumoral arsenic accumulation and inorganic phosphate deprivation were simultaneously observed, and arsenic concentration was much higher as ATONP was transarterially administered than ATO, or intravenously injected. Tumor necrosis and apoptosis were remarkably more severe in ATONP group than ATO, but no significant hepatic and renal toxicity was perceived. In brief, ATONP alleviated arsenic toxicity and boosted the therapeutic effect of TACE via Pi-activated drug sustainable release.

19.
Am J Transl Res ; 11(9): 5673-5688, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632539

RESUMO

Multiple sclerosis (MS), one of the autoimmune and inflammatory diseases, is a major cause of neurological disability worldwide. The existing clinical treatments are not curable, and better treatments are urgently needed. Mesenchymal stromal cells (MSCs) have shown promise for treating MS, but the favorable effects and mechanism of MSC therapy on MS are still not fully understood. In this study, we analyzed the phenotypic feature of peripheral blood mononuclear cells (PBMCs) in MS patients and found that the patients exhibited an increase in the frequency of B cells, but a markedly decrease in frequency of CD5+ and IL-10+ B cells compared to healthy controls. Infusion of MSCs exhibited a significant therapeutic effect on the experimental autoimmune encephalomyelitis (EAE) mice, infiltration of mononuclear cells and demyelination of the spinal cords were both reduced in CNS of the mice, the frequency of CD5+ IL-10+ B cells in the mice was significantly increased. Additionally, when PBMCs or B cells from MS patients were co-cultured with MSCs, the frequency of CD5+ IL-10+ B cells also increased, the proliferative and immunosuppressive capacity of CD5+ B cells were significantly enhanced while the apoptosis ratio of this cellular subset significantly decreased. Moreover, those effects could be eliminated while the indoleamine 2,3-dioxygenase (IDO) inhibitor, D/L-1MT, was added to the co-cultured cells. In summary, this study suggests that MSCs can control EAE via IDO pathway to promote the proportion and function of CD5+ IL-10+ B cells, providing a promise to treat patients with MS in the clinical setting.

20.
Zhongguo Fei Ai Za Zhi ; 22(10): 645-648, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31650947

RESUMO

Immune checkpoint inhibitors (ICIs) have been used more and more Increasingly in clinical oncology treatment, which has significantly improved the prognosis of cancer patients. Over-activation of T cells and related signaling pathways may cause immune-related adverse effects. Renal immune side-effects are relatively rare, but some of them are serious and fatal. This review analyses of the Incidence, clinical and pathological manifestations of ICIs-induced renal injury, and focuses on the differential diagnosis and treatment. Because there are many secondary factors that need to be differentiated from immune mechanism, renal biopsy should be performed if necessary to determine the important decision.

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