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1.
J Hazard Mater ; 402: 123563, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745876

RESUMO

Ingestion of nanoparticles may cause various damages to human body. However, how such ingestion by pregnant mother influences fetal development is not known because, presumably, ingested nanoparticles have to cross multiple biological barriers (such as intestinal and placental) to reach fetus. To answer this crucial question, here we investigated how a relatively biocompatible zirconia nanoparticles (ZrO2 NPs, 16 nm) were translocated to fetal brains in three exposure models of pregnant mice: Model 1, oral exposure of nanoparticles before maternal blood-placental barrier (BPB) was fully developed; Model 2, exposures after BPB was developed, but before fetal blood-brain-barrier (BBB) was fully developed; Model 3, exposures after both maternal BPB and fetal BBB were fully developed. Our experimental results showed that translocation of ZrO2 NPs into fetal brains was 55 % higher in Model 2 and 96 % higher in Model 1 compared with that in Model 3 after nanoparticles (50 mg/kg) were orally exposed to pregnant mice. Therefore, nanoparticles are able to cross multiple biological barriers and nanotoxicity to fetus is highly dependent on stages of pregnancy and fetal development or the maturity of multiple biological barriers. Oral exposures to nanoparticles during pregnancy are dangerous to fetal brain development, especially in early pregnancy.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 247: 119147, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33189982

RESUMO

In this paper, we have carried out high-level ab initio calculations on the electronic states of GeH+ with the configuration interaction method. The spin-orbit coupling (SOC), core-valence correlation (CV), scalar relativistic effects and Davidson correction (+Q) are included. The potential energy curves (PECs) of 13 Λ-S correlated with the four lowest dissociation limits and 32 Ω electronic states generated from those Λ-S states are obtained. Our results indicate that the first 3Σ- and second 3Π states are adiabatically correlated with the dissociation limit Ge(3Pg) + H+(1S), which is different from the previously reported Ge+(4Pg) + H(2Sg). From the computed PECs, the spectroscopic constants of the Λ-S and Ω states are determined, which are in good agreement with previous experiments. The dipole moments (DMs) for Λ-S electronic states are also investigated. With the help of spin-orbit coupling matrix involving the 13Σ- and 23Π states, the intricate couplings related with the crossing states are revealed, and the weak predissociation for ν' ≥0 vibrational levels of 13Σ- and the perturbations for vibrational levels of 21Σ+ (ν' ≥1) and 11Δ (ν' ≥0) states are analyzed. Finally, the transition properties of five transitions are predicted, including the Franck-Condon Factors (FCFs), transition dipole moments (TDMs), and the spontaneous radiative lifetimes of lower vibrational states. This study will improve our comprehension on the detailed electronic structure and spectroscopy of GeH+ radical cation.

3.
Mol Neurobiol ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219486

RESUMO

Recent genetic studies clearly indicate that variants in several lysosomal genes act as risk factors for idiopathic Parkinson's disease (PD). Variants in the co-activator of glucocerebrosidase gene (GBA) and the four active saposins (Sap A-D) which are encoded by the prosaposin gene (PSAP) are of particular interest; however, their genetic roles in PD are unknown. Whole-exome sequencing and Sanger sequencing were used to assess the genetic etiology of 400 autosomal dominant inherited PD (ADPD) and 300 sporadic PD (SPD) patients. Variants from public databases, including Genome Aggregation Database-East Asian (GnomAD_EAS) and Chinese Millionome Database (CMDB), were used as control groups. Burden analysis based on gene and domains level were performed to investigate the role of rare PSAP variants in PD. Six rare and likely pathogenic variants, located in the Sap A-D domains, were identified and accounted for 0.75% (3/400) of ADPD and 1.33% (4/300) of SPD in the Chinese population. Based on the gene or domain, burden analysis showed that damaging missense variants in SapC had statistical significance on the risk of developing PD. Interestingly, rs4747203, an intronic variant potentially linked to PSAP expression, was associated with reduced risk for PD (p = 8.6e-7 in GnomAD EAS and p = 0.002 in Chinese). Clinically, patients carrying the likely pathogenic variants presented typical PD motor symptoms and responded well to levodopa treatment. Six out of seven patients carrying the likely pathogenic variants of PSAP presented slow disease progression, and none of the patients developed cognitive impairment. Our study expands the spectrum of mutations associated with the risk of developing PD and enhances the understanding of the relationship of the clinical phenotype of PD with PSAP variants.

4.
PLoS One ; 15(11): e0239119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33137133

RESUMO

Autophagy is an important factor in liver ischemia-reperfusion injury. In the current study we investigate the function of interferon regulatory factor-1 (IRF1) in regulating autophagy to promote hepatic ischemia reperfusion injury (IR). The high expression of IRF1 during hepatic IR exhibited increased liver damage and was associated with activation of autophagy shown by Western blot markers, as well as immunofluorescent staining for autophagosomes. These effects were diminished by IRF1 deficiency in IRF1 knock out (KO) mice. Moreover, the autophagy inhibitor 3-MA decreased IR-induced liver necrosis and markedly abrogated the rise in liver injury tests (AST/ALT). ß-catenin expression decreased during liver IR and was increased in the IRF1 KO mice. Immunoprecipitation assay showed the binding between IRF1 and ß-catenin. Overexpression of IRF1 induced autophagy and also inhibited the expression of ß-catenin. ß-catenin inhibitor increased autophagy while ß-catenin agonist suppressed autophagy in primary mouse hepatocytes. These results indicate that IRF1 induced autophagy aggravates hepatic IR injury in part by inhibiting ß-catenin and suggests that targeting IRF1 may be an effective strategy in reducing hepatic IR injury.

6.
Dalton Trans ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146210

RESUMO

Three oxalate-bridging lanthanide-based polyoxometalates (Ln-POMs) K17Na2H5[{(As2W19O67(H2O))Ln(H2O)2}2(C2O4)]·50H2O. [Ln = Sm3+ (1), Pr3+ (2), and Ce3+ (3)] were successfully synthesized. The structures were further characterized by single-crystal X-ray diffraction analyses, Raman spectroscopy, elemental analyses, powder X-ray diffraction (PXRD), IR spectra, UV/vis diffuse reflectance spectroscopy, and thermogravimetric analysis (TGA). The structural characterization study reveals that Ln-POMs 1-3 crystallize in the form of the triclinic space group P1[combining macron] and consist of an oxalate bridging di-Ln3+-incorporated H-shaped dimer, which can also be viewed as a combination of two half-units {Ln(As2W19O67(H2O))(H2O)2}222- related by an inversion center. It is worth noting that the opening angle (33.01°) from the [As2W19O67(H2O)]14- fragment in 1-3 is less than that of the [As2W19O67(H2O)]14- precursor (40.99°). Furthermore, the stability of 1-3 in aqueous solution and their solid-state photoluminescence properties have also been investigated in this work.

7.
Dalton Trans ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146643

RESUMO

In this work, a series of transparent luminescent MOF thin films are designed and prepared by assembling lanthanide functionalized UiO-67 (Ln(TTA/TAA)@UMOF, Ln = Eu, Tb, Er, Nd, TTA = 2-thenoyltrifluoroacetone, TAA = 1,1,1-trifluoropentane-2,4-dione) on organosilane linker (L) modified Al2O3 (A) using lanthanide ions as the bridge. Notably, Ln(TTA/TAA)@UMOF is synthesized by introducing lanthanide ions and TTA/TAA into the framework of the UMOF via a facile and non-destructive post-synthesis modification (PSM) strategy. Because there are multiple antennas including L, the ligand of UMOF, and ß-diketone (TTA/TAA) transferring energy to lanthanide ions, these thin films exhibit excellent luminescence properties. Interestingly, the Eu@UMOF-Eu-LA film can selectively recognize ammonia without the interference of other indoor pollutant gases. Further investigation reveals that the Eu@UMOF-Eu-LA film sensor shows superior performances including quick response, outstanding selectivity and high sensitivity (LOD = 9 ppm) towards ammonia. These results illustrate that the Eu@UMOF-Eu-LA film has enormous potential to detect ammonia practically.

8.
Bioorg Chem ; 105: 104353, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33096311

RESUMO

Eleven undescribed schinortriterpenoids (SNTs) and one known analogue (12) were isolated from the stems and leaves of Schisandra henryi. Their diverse structures included preschisanartane (1), 18-norschiartane (2-5, 12), schiartane (6 and 7), and schisanartane (8-11) skeletons, which were elucidated by comprehensive NMR, MS, electronic circular dichroism analyses, single crystal X-ray diffraction and biogenetic considerations. 1 was the first case of preschisanartane-type SNT with six-membered lactone ring, and 2 was one of the most highly oxygenated 18-norschiartane SNTs. Three types of the highly oxygenated SNTs, 1, 4, 10 and 11, effectively prevent apoptosis induced by corticosterone in PC12 cells. In addition, 11 showed neurite outgrowth-promoting activity.

9.
J Periodontol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33094479

RESUMO

BACKGROUND: Occlusal trauma can aggravate periodontitis, but the mechanism remains unclear. Yes-associated protein (YAP), a mechanical stressor protein, may play an important role in this process. METHODS: Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect the expression of YAP and inflammatory factors in patients with periodontitis accompanied with or without occlusal trauma. Through local administration of Porphyromonas gingivalis and composite resin bonding on maxillary molars in mice, we established periodontitis and occlusal trauma models. Treatment with or without XAV939, to inhibit YAP activation, was performed in these models. Micro-computed tomography, immunofluorescence (IF), and qRT-PCR were used to explore the YAP pathway in periodontitis with occlusal trauma. Cyclic stress and lipopolysaccharide (LPS) stimuli were applied to the L929 mouse fibroblast cell line with or without XAV939. Western blot, IF, and qRT-PCR were used to verify the in vivo results. RESULTS: Activated dephosphorylated YAP and increased expression of inflammatory factors were observed in patients with periodontitis accompanied with occlusal trauma. In the mouse model of periodontitis with occlusal trauma, YAP transferred into the nucleus, resulting in Jun N-terminal kinases (JNK) related pro-inflammatory pathway up-regulation. L929 cell cyclic stress and LPS stimulation results confirmed the in vivo results. Application of XAV939 inhibited YAP protein dephosphorylation and reduced JNK pro-inflammatory pathway factor expression in vivo and in vitro. CONCLUSIONS: Occlusal trauma can activate YAP nuclear transfer, resulting in the up-regulation of the JNK pro-inflammatory pathway. This can be inhibited by the XAV939 YAP inhibitor.

10.
World J Gastroenterol ; 26(37): 5646-5660, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33088158

RESUMO

BACKGROUND: At present, the enhanced recovery after surgery (ERAS) protocol is widely implemented in the field of gastric surgery. However, the effect of the ERAS protocol on the long-term prognosis of gastric cancer has not been reported. AIM: To compare the effects of ERAS and conventional protocols on short-term outcomes and long-term prognosis after laparoscopic gastrectomy. METHODS: We retrospectively analyzed the data of 1026 consecutive patients who underwent laparoscopic gastrectomy between 2012 and 2015. The patients were divided into either an ERAS group or a conventional group. The groups were matched in a 1:1 ratio using propensity scores based on covariates that affect cancer survival. The primary outcomes were the 5-year overall and cancer-specific survival rates. The secondary outcomes were the postoperative short-term outcomes and inflammatory indexes. RESULTS: The patient demographics and baseline characteristics were similar between the two groups after matching. Compared to the conventional group, the ERAS group had a significantly shorter postoperative hospital day (7.09 d vs 8.67 d, P < 0.001), shorter time to first flatus, liquid intake, and ambulation (2.50 d vs 3.40 d, P < 0.001; 1.02 d vs 3.64 d, P < 0.001; 1.47 d vs 2.99 d, P < 0.001, respectively), and lower medical costs ($7621.75 vs $7814.16, P = 0.009). There was a significantly higher rate of postoperative complications among patients in the conventional group than among those in the ERAS group (18.1 vs 12.3, P = 0.030). Regarding inflammatory indexes, the C-reactive protein and procalcitonin levels on postoperative day 3/4 were significantly different between the two groups (P < 0.001 and P = 0.025, respectively). The ERAS protocol was associated with significantly improved 5-year overall survival and cancer-specific survival rates compared with conventional protocol (P = 0.013 and 0.032, respectively). When stratified by tumour stage, only the survival of patients with stage III disease was significantly different between the two groups (P = 0.044). CONCLUSION: Adherence to the ERAS protocol improves both the short-term outcomes and the 5-year overall survival and cancer-specific survival of patients after laparoscopic gastrectomy.

11.
Inorg Chem ; 59(20): 15088-15100, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33006286

RESUMO

With the judicious selection of an appropriate semirigid polycarboxylate, 2,5-bis(3',5'-dicarboxylphenyl)benzoic acid (H5bdba), and an inorganic metal ion, a novel anionic framework, {[NH2(CH3)2]2·[Cd3.5(bdba)(Hbdba)(H2O)1.5]}n (Cd-MOF), has been synthesized solvothermally. Single-crystal measurement results show that the prepared Cd-MOF features a three-dimensional structure containing two types of one-dimensional channels, and as we expected, there exist accessible uncoordinated -COOH groups on Hbdba pointing toward the rhombus channels. Powder X-ray diffraction and thermogravimetric analysis measurements were performed for the thermal and chemical stability analysis of Cd-MOF. In addition, the lanthanide(III)-functionalized hybrids, Ln(III)@Cd-MOF, were initially prepared by coordinated postsynthetic modification to incorporate luminescent Ln(III) ions into the structure. The luminescence properties of the hybrids are studied, and the results show notable and specialized fluorescent sensitization of Cd-MOF to Tb(III) ions. Moreover, the Tb(III)@Cd-MOF hybrid with outstanding fluorescence properties was developed as a highly sensitive and selective luminescent probe for the biomarker diphenyl phosphate (DPP) based on multiquenching effects. Tb(III)@Cd-MOF is the first case to realize the detection of urinary DPP through lanthanide metal-organic framework fluorescence spectrometry and shows practical detection potential.

12.
Anal Chem ; 92(20): 13971-13979, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32970421

RESUMO

Digitalizing complex nanostructures into data structures suitable for machine learning modeling without losing nanostructure information has been a major challenge. Deep learning frameworks, particularly convolutional neural networks (CNNs), are especially adept at handling multidimensional and complex inputs. In this study, CNNs were applied for the modeling of nanoparticle activities exclusively from nanostructures. The nanostructures were represented by virtual molecular projections, a multidimensional digitalization of nanostructures, and used as input data to train CNNs. To this end, 77 nanoparticles with various activities and/or physicochemical property results were used for modeling. The resulting CNN model predictions show high correlations with the experimental results. An analysis of a trained CNN quantitatively showed that neurons were able to recognize distinct nanostructure features critical to activities and physicochemical properties. This "end-to-end" deep learning approach is well suited to digitalize complex nanostructures for data-driven machine learning modeling and can be broadly applied to rationally design nanoparticles with desired activities.

13.
Int Arch Allergy Immunol ; : 1-11, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32927462

RESUMO

INTRODUCTION: The recurrence occurs frequently among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and predictors that could be conveniently detected during practice in outpatient service are needed. OBJECTIVE: We aimed to illustrate that the concentration of Charcot-Leyden crystal (CLC) in nasal secretions can effectively and noninvasively predict polyp recurrence. METHODS: 108 patients with CRSwNP were divided into recurrence (n = 68) and recurrence-free (n = 40) groups. Preoperative CLC concentrations in nasal secretions were collected and detected by ELISA. Polyp tissues were harvested during biopsy or endoscopic sinus surgery and were evaluated for inflammatory cells by histopathological staining. Demographic information and the clinical characteristics of each patient were reviewed for associations with recurrence. Binary logistic regression analysis was performed to determine predictive factors for polyp recurrence. Receiver operating characteristic (ROC) curves and the Youden index were performed to determine their predictive values. Survival analysis was performed to compare recurrence risk of patients with different CLC concentrations. RESULTS: Sixty-eight (62.96%) patients developed recurrence during a 12- to 33-month postoperative follow-up. CLC concentrations in nasal secretions were positively correlated with eosinophil percent in polyp tissue and peripheral blood and were significantly higher in patients of the recurrence group than in the patients of the recurrence-free group (p < 0.001). Binary logistic regression and ROC curve demonstrated that CLC protein in nasal secretions is predictive of polyp recurrence. According to the Youden index, a CLC concentration of 34.24 ng/mL can predict postoperative polyp recurrence with 92.6% sensitivity and 87.5% specificity. Patients with CLC concentrations higher than the cutoff value yielded a higher risk of recurrence (p < 0.001, HR = 11.31, 95% CI: 6.41-19.98). CONCLUSIONS: CLC protein in nasal secretions may serve as a promising noninvasive biomarker to predict CRSwNP recurrence.

14.
Clin Exp Rheumatol ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32896243

RESUMO

OBJECTIVES: We aimed to reveal evidence of endothelial dysfunction in the development of anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM). METHODS: Thirty anti-MDA5 DM patients were enrolled and compared with patients with polymyositis (PM) (n=10) and healthy controls (n=20). The concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and von Willebrand factor (vWF) as well as interferon-alpha (IFN-α) and Galcetin-9 in the peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma levels of sICAM-1, sVCAM-1, ET-1 and vWF were higher in the anti-MDA5 DM patients than in either the healthy controls or the PM patients. In the anti-MDA5 DM cohort, the ET-1 and vWF levels were significantly lower in the cases without cutaneous ulcers and ILD than the other cases. There was a strong positive relationship between the concentrations of ET-1 and Galectin-9 in the anti-MDA5 DM group. CONCLUSIONS: Our data suggest that endothelial dysfunction may be involved in the development of anti-MDA5 DM.

15.
Org Lett ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32996768

RESUMO

Phosphine ligands with up to six chiral sites were prepared, starting from 2-phenylphenol, via O- and P-alkylation, cyclization, and coupling. The chirality was transferred from (L)-menthyl to phosphorus, α-carbon, and axis, to achieve excellent diastereoselectivities. During an intramolecular SNAr reaction with alkoxyl as the leaving groups, the C-O bond was converted to a C-C bond. Both phosphine boranes and oxides could be used for the conversions, affording a series of cyclic phosphines.

16.
J Am Chem Soc ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32960585

RESUMO

This work reports on the structural and photophysical characterization of D4-symmetrical octanuclear circular LnIII helicates, [(R)- or (S)-iPr-Pybox]8(LnIII)8(THP)8 (where Ln = Eu and Tb, THP = trianionic tris-ß-diketonate, and iPr-Pybox = chiral bis(4-isopropyl-2-oxazolinyl)pyridine). X-ray crystallographic analysis revealed that the octanuclear circular helicate possesses square antiprism architecture and consists of four [(R)- or (S)-iPr-Pybox]2LnIII2(THP)2 asymmetric units arranged in a closed ring form. Ligand-to-ligand interactions between the THP and the iPr-Pybox ligands have successfully directed formation of enantiopure, homoconfigurational (Δ,Δ,Δ,Δ,Δ,Δ,Δ,Δ)-R and (Λ,Λ,Λ,Λ,Λ,Λ,Λ,Λ)-S isomers. All of the nonacoordinated LnIII ions are identical and exhibit a distorted capped square antiprism (CSAP) geometry. Upon excitation of the ligand absorption band (λ = 360 nm), the circular helicates display characteristic EuIII (red, 5D0 → 7FJ, J = 0-4) or TbIII (green, 5D4 → 7FJ, J = 6-3) core f-f luminescence. The overall emission quantum yields of the circular EuIII and TbIII helicates are 0.145 and 0.0013, respectively, in chloroform. The EuIII and TbIII complexes exhibit remarkable circularly polarized luminescence (CPL) activity at their magnetic dipole transition with observed luminescence dissymmetry factors |glum| of 1.25 (5D0 → 7F1, λ = 592 nm) and 0.25 (5D4 → 7F5, λ = 541 nm), respectively. Exceptional |glum| values of the circular EuIII helicates highlight the visible intensity difference between left and right circularly polarized emissions of R and S isomers in chloroform and PMMA thin film.

17.
J Colloid Interface Sci ; 583: 50-57, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32971505

RESUMO

17ß-Estradiol (E2), an important endocrine disrupting compound, could be quantitatively detected by fluorescence resonance energy transfer (FRET) aptasensor, designed in this paper. Metal organic frameworks have large specific surface area and easily modifiable groups, which are helpful for the construction of aptasensor. Specifically, streptavidin was immobilized on the synthesized MIL-53-NH2 by covalent bonding, and further linked with the biotin modified E2 aptamer (apt) through specific bonding between avidin and biotin to obtain the FRET donor probe (MIL-53-apt). Meanwhile, complementary DNA (cDNA) modified Ru(bpy)32+-doped silica nanoparticles (RuSiO2-cDNA) were prepared through covalent bonding. They acted as the FRET acceptor probe, since its absorption spectrum showed large overlap with the emission spectrum of MIL-53-apt. In the presence of E2, aptamer modified donor probes tended to bind with E2, owing to their higher selectivity and affinity. Therefore, the optimal distance between FRET pairs was broken, resulting in the fluorescence emission recovery of donor and the fluorescence emission of acceptor decreased. Under optimal conditions, this proposed aptasensor displayed sensitive detection of E2 ranging from 0.5 to 1000 nM with a detection limit of 0.2 nM. Furthermore, the sensor provides a promising method for rapid and sensitive detection of other small biological molecules.

18.
Mol Clin Oncol ; 13(5): 63, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32963782

RESUMO

The prognostic role of the neutrophil-to-lymphocyte ratio (NLR) has been reported in colorectal cancer (CRC); however, its variation and corresponding predicative value in patients undergoing resection remain largely unknown. In the present study, data from 146 patients with CRC were retrospectively collected, optimal cut-off points for preoperative and postoperative low and high NLRs were set, and ΔNLR was calculated. Subsequently, patients were classified into low-low, low-high, high-low and high-high subgroups based on the cut-off points, and their progression-free survival (PFS) was determined. A Cox proportional hazard model was applied to calculate the prognostic value of all factors. The results demonstrated that both preoperative and postoperative NLRs (pre-NLR and post-NLR) but not ΔNLR could predict PFS with optimal cut-off points of 2.39 and 2.96, respectively. For predicting PFS, the pre-NLR had a sensitivity and specificity of 48.80 and 79.50%, respectively, and the post-NLR had a sensitivity and specificity of 63.20 and 56.20%, respectively. Significant differences were identified between low and high pre-NLRs in terms of histological grade (P<0.01) and tumor diameter (P<0.01); however, such differences were only found in terms of age (P<0.01) for low and high post-NLRs. The PFS of patients in the low-low, low-high, high-low and high-high subgroups was 50.30±21.36, 43.67±22.78, 31.06±25.56 and 29.87±24.13 months, respectively, and patients in the high-high subgroup had the worst PFS (P<0.01). Preoperative CEA level, invasive depth, node involvement, distant metastasis and preoperative NLR were independent prognostic factors. In conclusion, a persistently high NLR for patients with CRC undergoing resection was associated with poor prognosis.

19.
Breast Cancer Res Treat ; 184(2): 397-405, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32776291

RESUMO

BACKGROUND AND PURPOSE: Paclitaxel-based regimens are widely used in the neoadjuvant therapy (NAT) of breast cancer. The purpose is to analysis the efficacy and adverse events (AEs) among common paclitaxel (PTX), docetaxel and liposomal paclitaxel. At the same time, we want to analysis the axillary nodal pathologic complete response (apCR) after NAT among the three groups. METHODS: From April 2014 to 2020, 647 breast cancer patients underwent operation after NAT were included in this study. Patients received full course of anthracycline- and paclitaxel-based chemotherapy before surgery. The paclitaxel-based regimens included PTX, docetaxel and liposomal paclitaxel. The therapy efficacy and AEs of the three groups were evaluated. At the same time, the apCR was also analyzed. RESULTS: In general, 30.6% (198/647) of patients achieved breast pathologic complete response (bpCR), which was 28.6%, 28.3% and 39.3% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.067). The total pathologic complete response (tpCR) (achieving both bpCR and apCR) was 21.6% (140/647). The tpCR was 13.3%, 19.4% and 34.4% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.026). The multivariate logistic analysis result showed that clinical tumor stage and molecular subtype were significantly associated with tpCR (all p < 0.05). Among 592 clinical positive patients (cN+), the apCR was 39.0% (231/592). The multivariate logistic analysis showed that paclitaxel- based regimens and molecular subtype were indicated as independent predictors for apCR of NAT. The apCR was significantly higher in liposomal paclitaxel group (63.5%) than in PTX (24.6%) and docetaxel group (34.8%) (p < 0.001). The subgroup analysis among different molecular subtypes found that in triple negative (TN) and HER-2 positive (HER2+) subgroup, the apCR in liposomal paclitaxel group was significantly higher than those in PTX and docetaxel group (all p < 0.05). But no significant result was found in the subgroup analysis in hormone receptor positive/HER-2 negative subgroup (p = 0.050). Safety analysis indicated that the incidence of neutropenia (grade III-IV) and peripheral neurotoxicity (grade I-II) was significantly lower in the liposomal paclitaxel group than in the PTX and docetaxel group. The incidence of oral mucositis, anaphylaxis and palmar-plantar erythrodysesthesia syndrome was also much lower in liposomal paclitaxel than other two groups (all p < 0.05). And there was no significant difference in other AEs among the three groups (all p > 0.05). CONCLUSION: Liposome paclitaxel had similar tumor suppressor effect compared with PTX and docetaxel in NAT setting. Moreover, it had a better axillary lymph node (ALN) response after NAT than PTX and docetaxel. These patients who received liposome paclitaxel had more chance to avoid ALN dissection after NAT. At the same time, the application of liposome enables liposome paclitaxel could significantly reduce AEs caused by chemotherapy. Therefore, we suggested the application of liposome paclitaxel in the NAT setting, especially for cN+ patients with TN and HER2 + disease.

20.
Biochem Biophys Res Commun ; 531(3): 275-281, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32800559

RESUMO

MicroRNAs (miRNA) are believed to play a crucial role in the cause and treatment of temporal lobe epilepsy (TLE) by controlling gene expression in different stages of the disease. To investigate role of miRNA in the latent stage following status epilepticus, we first compared microRNA expression profiles in mice hippocampus at 1 week after pilocarpine-induced status epilepticus (SE) vs. controls in hippocampal tissues using Exiqon miRCURY LNA™ miRNAs Array. Then, the target genes of altered miRNAs were predicted using both TargetScan 7.1 and miRDB V5, and were further selected by intersecting with another independent mRNA expression profile dataset from the samples at the same time point. We found out 14 common genes as down miRNA target (up-mRNA) and 4 common genes as up miRNA target (down mRNA) in SE mice. miR-669m-3p-TRHR (thyrotropin releasing hormone receptor), miR-669m-3p-B3galt2 (ß-1,3-Galactosyltransferase 2), miR-105-PDPN (Podoplanin) and miR-883b-3p-CLEC-2 (C-type-lectin-like-2) were found to be potential molecular mechanisms to modulate the calcium signaling pathway, glycosylation pathways and chemokine mediated inflammatory processes in mice hippocampus at 1 week after pilocarpine-induced SE, respectively. Our results offered potential novel insights into the cellular events in the mice hippocampus mediated by miRNASs-target genes that shape SE-evoked epileptogenesis.

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