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1.
J Clin Lab Anal ; : e24094, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741349

RESUMO

BACKGROUND: Ferroptosis is a novel iron-dependent form of cell death, which is implicated in various diseases including cancers. However, the influence of ferroptosis-related genes on the prognosis of breast cancer remains unclear. METHODS: RNA sequencing data of 1053 breast cancer tissue samples and 111 normal tissue samples from The Cancer Genome Atlas (TCGA) were analyzed. Expression levels of 259 ferroptosis-related genes were compared. Gene Ontology (GO) and the Kyoto Gene and Genomic Encyclopedia (KEGG) analyses were conducted on differentially expressed genes. Cox univariate analysis was conducted to explore the potential prognostic biomarkers of breast cancer. Infiltrating immune cell status was assessed. RESULTS: A total of 66 ferroptosis-related genes were differentially expressed in breast cancer tissues. The enriched GO terms included Biological Process (mainly included response to oxidative stress, cellular response to chemical stress, multicellular organismal homeostasis, cofactor metabolic process, response to metal ion, response to steroid hormone, cellular response to oxidative stress, transition metal ion homeostasis, iron ion homeostasis, and cellular iron ion homeostasis), Cellular Component (mainly included apical plasma membrane, early endosome, apical part of cell, lipid droplet, basolateral plasma membrane, blood microparticle, clathrin-coated pit, caveola, astrocyte projection, and pronucleus) and Molecular Function (mainly included iron ion binding, ubiquitin protein ligase binding, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor, ferric iron binding, aldo-keto reductase (NADP) activity, oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, steroid dehydrogenase activity, alditol:NADP+1-oxidoreductase activity, and alcohol dehydrogenase (NADP+) activity). The enriched KEGG pathway mainly included the HIF-1 signaling pathway, NOD-like receptor signaling pathway, ferroptosis, IL-17 signaling pathway, central carbon metabolism in cancer, PPAR signaling pathway, PD-L1 expression, and PD-1 checkpoint pathway in cancer. Among them, 38 ferroptosis-related genes were significantly associated with the prognosis of breast cancer. The prognostic model was constructed, and breast cancer patients in low-risk group had a better prognosis. In addition, risk score of ferroptosis prognostic model was negatively correlated with B cells (r = -0.063, p = 0.049), CD8+ T cells (r = -0.083, p = 0.010), CD4+ T cells (r = -0.097, p = 0.002), neutrophils (r = -0.068, p = 0.033), and dendritic cells (r = 0.088, p = 0.006). CONCLUSIONS: The ferroptosis pathway plays a key role in breast cancer. Some differentially expressed ferroptosis-related genes can be used as prognostic biomarkers for breast cancer.

2.
Nat Commun ; 12(1): 6711, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795238

RESUMO

Cancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness.

3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 561-565, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816674

RESUMO

Objective: To investigate the effects of inhibition of lncRNA PVT1 on the proliferation, apoptosis and oxidative stress of vascular endothelial cells induced by hyperglycemic. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and divided into four groups: control group (5.5 mmol/L glucose), high glucose group (30 mmol/L glucose), high glucose + siNC group (30 mmol/L glucose +siNC, negative control group), HG + siPVT1 group (30 mmol/L glucose + siPVT1, lncRNA PVT1 silencing group). The expression of PVT1 after transfection was detected by quantitative real-time PCR. MTT assay was used to detect the effect of siPVT1 (small interfering RNA PVT1) on the proliferation of HUVECs cells induced by high glucose. Flow cytometry was used to detect ROS and apoptosis of HUVECs cells induced by siPVT1. Western blot was used to detect the expression levels of apoptotic proteins such as Bax, Bcl-2, and cleaved caspase-3 in HUVECs cells. Results: Compared with the control group, after transfection with siPVT1, the expression level of PVT1 was decreased significantly (P<0.05). MTT results showed that the proliferation activity of HUVECs cells in the high-glucose group was reduced significantly after 24 h and 48 h. Compared with the HG + siNC group, the proliferation activity of HUVECs cells in the HG + siPVT1 group was increased significantly (P<0.05) after 24 h and 48 h. Flow cytometry results showed that ROS and apoptosis rate of HUVECs cells in the high-glucose group were increased significantly compared with the control group. Compared with the HG + siNC (negative control) group, ROS and apoptosis rates of HUVECs cells in the HG + siPVT1 group were reduced significantly. Compared with the control group, the expression levels of cleaved-caspase-3 and Bax in the high-glucose group were significantly up-regulated, while the expression level of Bcl-2 was down-regulated. Compared with the HG + siNC group, the expression levels of cleaved-caspase-3 and Bax were down-regulated, and the expression level of Bcl-2 was up-regulated. The differences were statistically significant (P<0.05). Conclusion: Inhibition of lncRNA PVT1 can significantly increase the proliferation activity of HUVECs cells induced by hyperglycemia, reduce oxidative stress and inhibit cell apoptosis.


Assuntos
Hiperglicemia , RNA Longo não Codificante , Apoptose , Proliferação de Células , Células Cultivadas , Glucose , Células Endoteliais da Veia Umbilical Humana , Humanos , Estresse Oxidativo , RNA Longo não Codificante/genética
4.
Lancet Infect Dis ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838200

RESUMO

Cutaneous infection by Balamuthia mandrillaris is a rare condition that is sometimes complicated by life-threatening CNS involvement. It often evades timely diagnosis due to its rarity and non-specific clinical manifestations. Patients can be either immunocompetent or immunocompromised. It is probably transmitted via inhalation or inoculation through broken skin, and then spreads to the brain and other organs through haematogenous spread. It is important for clinicians to be aware of this disease because rapid diagnosis and subsequent therapy has, in some cases, been associated with survival. In this Grand Round, we report the case of a 7-year-old boy who presented with large, chronic plaques on his face. Several biopsies showed non-specific granulomatous inflammation. The patient deteriorated rapidly and died within 1 month of displaying abnormal symptoms in the CNS. Immunohistochemical staining of skin tissue identified B mandrillaris as the infectious agent. The diagnosis was confirmed with PCR, which detected B mandrillaris DNA in formalin-fixed skin tissue sections. B mandrillaris infection should be considered in the differential diagnosis of patients with chronic granulomatous lesions. We also reviewed the epidemiology, B mandrillaris in nature and in the laboratory, clinical manifestations, histopathology, diagnosis, and treatment of infection.

5.
Front Microbiol ; 12: 721441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616383

RESUMO

Sugarcane cropping systems receive elevated application of nitrogen (N) fertilizer for higher production, which may affect production costs and cause environmental pollution. Therefore, it is critical to elucidate the response of soil microbial to N fertilizer inputs in sugarcane soil. A field experiment was carried out to investigate the effects of optimum (N375, 375 kg N/ha) and excessive (N563, 563 kg N/ha) amounts of N fertilizer on soil bacterial diversity and community structure in a sugarcane cropping system by MiSeq high-throughput sequencing; 50,007 operational taxonomic units (OTUs) were obtained by sequencing the 16S rRNA gene amplicons. Results showed that the most abundant phyla in the sugarcane rhizosphere soil were Proteobacteria, Actinobacteria, Acidobacteria, and Planctomycetes, whose ensemble mean accounted for 74.29%. Different amounts of N application indeed change the bacterial diversity and community structures. Excessive application of N fertilizers significantly decreased the pH and increased the available N in soils and unexpectedly obtained a lower yield. Excessive N resulted in a relatively lower bacterial species richness and significantly increased the relative abundance of phyla Proteobacteria, Acidobacteria, and Bacteroidetes and the genera Sphingomonas and Gemmatimonas, while optimum N treatment significantly increased the phylum Actinobacteria and the genera Bacillus and Nitrospira (P < 0.05). N application shifted the N cycle in nitrification, mainly on the Nitrospira, but showed no significant effect on the genera related to nitrogen fixation, methane oxidation, sulfate reduction, and sulfur oxidation (P > 0.05). Overall, the optimum amount of N application might be conducive to beneficial microorganisms, such as Actinobacteria, Nitrospira, and Bacillus and, thus, result in a healthier ecosystem and higher sustainable crop production.

6.
Ann Palliat Med ; 10(9): 9398-9405, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628865

RESUMO

BACKGROUND: A peripherally inserted central catheter (PICC) effectively reduces frequent vein punctures in cancer patients. With increasing clinical applications, PICC-associated infections are attracting increasing attention. In this study, we retrospectively analyzed PICC-associated infections in chemotherapy patients treated at our hospital in recent years to identify risk factors for PICC-associated infections and the preventive effect of a self-efficacy intervention program. METHODS: Using a convenience sampling method, we selected 159 cancer patients who received chemotherapy through a PICC at our hospital between July 2017 and December 2018, and the patients were randomly divided to an observation group (n=79) and a control group (n=80) using a random number table. The control group received conventional intervention, and the observation group received a self-efficacy intervention. We analyzed self-efficacy scores before and after the intervention, the complication rate, the infection rate, pathogens identified, and risk factors for PICC-associated infections. RESULTS: Among the 159 chemotherapy patients, 26 (16.35%) experienced PICC-associated infections in this finished trial. Univariate analysis showed that sex, puncture site, and steroid use were unrelated to PICC-associated infections (P>0.05), whereas PICC indwelling time, white blood cell (WBC) count, a history of diabetes, and immunity were significantly related to PICC-associated infections (P<0.05). The self-efficacy score improved after the intervention in both groups, especially in the observation group (P<0.05). The incidence of complications such as catheter infection, catheter blockage, and catheter displacement was significantly lower in the observation group than in the control group (16. 67% vs. 88.10%; P<0.05). CONCLUSIONS: The self-efficacy intervention improves self-management and reduces complications in cancer patients receiving chemotherapy through a PICC. PICC indwelling time, WBC count, a history of diabetes, and immunity are independent risk factors for PICC-associated infections; thus, measures should be implemented to prevent infections. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100050651.


Assuntos
Cateterismo Venoso Central , Autoeficácia , Cateterismo Venoso Central/efeitos adversos , Cateteres , Humanos , Estudos Retrospectivos , Fatores de Risco
7.
Biomed Res Int ; 2021: 7878752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692842

RESUMO

Objective: To evaluate the effect of prepregnancy lymphocyte active immunotherapy on unexplained recurrent miscarriage, pregnancy success rate, and maternal-infant outcome. Methods: A total of 124 patients with recurrent miscarriage admitted to our hospital from January 2018 to December 2020 were selected as the research objects and divided into the experimental group and the control group according to the random number table method, with 62 patients in each group. The experimental group was treated with lymphocyte active immunotherapy, and the control group was given conventional treatment. The pregnancy success rate, estrogen indexes, hemorheology indexes, and psychological state of the two groups were compared. Results: The experimental group garnered a notably higher pregnancy success rate and a prominently lower miscarriage rate than the control group (P < 0.05). Better results of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed in the experimental group, as compared to the control group (P < 0.05). The experimental group yielded more desirable results in terms of treatment satisfaction, estrogen indexes, and hemorheology indexes in comparison with the control group (P < 0.05). Conclusion: The use of lymphocyte active immunotherapy for patients with unexplained recurrent miscarriage can significantly increase the pregnancy success rate, optimize the maternal-infant outcome, drive down the miscarriage rate, and ameliorate the patient's estrogen levels and hemorheology indicators, which is worthy of promotion and application in clinical practice.

8.
Huan Jing Ke Xue ; 42(11): 5405-5413, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708979

RESUMO

Nitrogen leaching loss in paddy fields is one of the main ways of farmland non-point source pollution. To explore the suitable fertilization of rice fields in the Erhai Lake Basin and reduce the nitrogen loss from paddy fields, a field experiment was conducted by setting single applications of chemical or organic fertilizer, combined organic and inorganic application, and single application of controlled release fertilizer under reduced nitrogen conditions. The results showed that, compared with the conventional fertilization treatment(CF), there was no significant difference in rice grain and straw yield between the single chemical fertilizer treatment(T1) and the organic-inorganic combined treatment(T3); the single organic fertilizer treatment(T2) decreased the rice grain yield by 13.0%, and decreased straw yield by 17.1%; single application of controlled-release fertilizer(T4) increased rice grain and straw yield by 15.7% and 21.0%, respectively. Further, compared with CF, the single application of chemical fertilizer(T1), organic fertilizer(T2), and organic-inorganic combined application(T3) reduced the total nitrogen leaching loss at 30 cm depths by 26.9%, 18.0%, and 33.9%, respectively. The loss of ammonia nitrogen leaching with T1, T2, and T3 decreased by 24.4%, 36.9%, and 36.6%, respectively, and the loss of nitrate nitrogen leaching decreased by 40.2%, 4.8% and 46.4%. The total nitrogen leaching at 60 cm soil depths was reduced by 34.2%, 26.3%, and 42.1%, the loss of ammonia nitrogen leaching was reduced by 31.4%, 35.7%, and 46.6%, and the loss of nitrate nitrogen leaching was reduced by 8.0%, 10.1%, and 23.9% for T1, T2, and T3, respectively. The total nitrogen loss at 30 and 60 cm depths increased by 41.6% and 14.0% in the single application of controlled release fertilizer(T4) treatment. Considering factors such as agronomic and environmental benefits of different fertilization modes, T1 and T3 are suitable environmentally friendly alternative fertilization modes.


Assuntos
Nitrogênio , Oryza , Agricultura , Fertilização , Fertilizantes , Nitrogênio/análise , Solo
9.
Neuroscience ; 479: 48-59, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648865

RESUMO

Diagnosis of major depressive disorder (MDD) is perplexing due to its multifactorial etiologies. Here, we isolated exosomes from the peripheral blood of MDD patients and healthy control subjects for mass spectrometry-based label-free quantitative proteomics. We identified that SERPINF1 is significantly diminished in the peripheral blood-derived exosomes of MDD patients compared to the healthy control subjects. Through RNA immunoprecipitation and luciferase reporter assays, we validated that SERPINF1 is a target of miR-186-5p that is upregulated in MDD patients' blood. In vivo studies in the chronic unpredictable mild stress (CUMS) mice further demonstrated that SERPINF1 in hippocampus is suppressed by miR-186-5p. Inhibiting the microRNA significantly restores the hippocampal SERPINF1 mRNA and protein expression, and ameliorates the depressive-like behaviors including sucrose preference and extended immobility time in the forced swim test. Instead, overexpressing miR-186-5p through tail intravenous injection of the mimics molecularly and behaviorally phenocopies the CUMS mice in wild-type mice. Our results indicate that the exosomal SERPINF1 in peripheral blood could serve as a reliable biomarker indicating MDD development, and miR-186-5p is a potential therapeutic target for the disease.

10.
J Hazard Mater ; 416: 125931, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492861

RESUMO

Contamination characteristics, equilibrium partitioning and risk assessment of phthalate esters (PAEs) were investigated in seawater, sediment and biological samples collected from the Xiangshan Bay area during an annual investigation between January and November 2019. PAE concentrations detected in the mariculture environment in surface seawater, sediment, and biological samples were 172-3365 ng/L, 190-2430 µg/kg (dry weight [dw]), and 820-4926 µg/kg (dw), respectively. The dominant congeners in different media included di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and di(2-ethylhexyl) phthalate (DEHP). The inner bay and the bay mouth were the gathering area of PAEs and heavily influenced by the mariculture activities, river inputs, and anthropogenic activities. The bioaccumulation of PAEs demonstrated benthic feeding fishes with relatively high trophic levels concentrated high levels of phthalates. The mobility of PAEs in sediment-seawater showed that the transfer tendency of low-molecular weight species was from the sediment to the water, which was in contrast with those of high-molecular weight PAEs. DEHP, DiBP and DnBP had various degrees of ecological risks in the aquatic environment, whereas only the DiBP posed potential risks in sediments. The current assessment of carcinogenic and noncarcinogenic risks posed by fish consumption were within acceptable limits for humans.


Assuntos
Ésteres , Ácidos Ftálicos , Aquicultura , China , Dibutilftalato , Humanos , Ácidos Ftálicos/toxicidade , Plásticos/toxicidade , Medição de Risco
11.
Front Pediatr ; 9: 710720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485199

RESUMO

Background: The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Methods: Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. Results: There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Conclusions: Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.

12.
Cancers (Basel) ; 13(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34503297

RESUMO

Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC. The current understanding and management of pRCC remain poor. We report here OIP5 being a novel oncogenic factor and possessing robust prognostic values and therapeutic potential. OIP5 upregulation is observed in pRCC. The upregulation is associated with pRCC adverse features (T1P < T2P < CIMP, Stage1 + 2 < Stage 3 < Stage 4, and N0 < N1) and effectively stratifies the fatality risk. OIP5 promotes ACHN pRCC cell proliferation and xenograft formation; the latter is correlated with network alterations related to immune regulation, metabolism, and hypoxia. A set of differentially expressed genes (DEFs) was derived from ACHN OIP5 xenografts and primary pRCCs (n = 282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (p < 2 × 10-16) and relapse (p < 2 × 10-16) possibilities. High-risk tumors stratified by Overlap66 risk score possess an immune suppressive environment, evident by elevations in Treg cells and PD1 in CD8 T cells. Upregulation of PLK1 occurs in both xenografts and primary pRCC tumors with OIP5 elevations. PLK1 displays a synthetic lethality relationship with OIP5. PLK1 inhibitor BI2356 inhibits the growth of xenografts formed by ACHN OIP5 cells. Collectively, the OIP5 network can be explored for personalized therapies in management of pRCC patients.

13.
Biomedicines ; 9(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34572270

RESUMO

HM-3, an integrin antagonist, exhibits anti-tumor biological responses and therefore has potential as a therapeutic polypeptide. However, the clinical applications of HM-3 are limited by its short half-life. In this study, we genetically fused human serum albumin (HSA) to the N or C-terminus of HM-3 to improve HM-3 pharmacokinetics. HM-3/HSA proteins were successfully expressed in Pichia pastoris and displayed improved pharmacokinetic properties and stability. Among them, the half-life of HM-3-HSA was longer than HSA-HM-3. In vitro, the IC50 values of HSA-HM-3 and HM-3-HSA were 0.38 ± 0.14 µM and 0.25 ± 0.08 µM in B16F10 cells, respectively. In vivo, the inhibition rates of B16F10 tumor growth were 36% (HSA-HM-3) and 56% (HM-3-HSA), respectively, indicating antitumor activity of HM-3-HSA was higher than HSA-HM-3. In conclusion, these results suggested that the HM-3/HSA fusion protein might be potential candidate HM-3 agent for treatment of melanoma and when HSA was fused at the C-terminus of HM-3, the fusion protein had a higher stability and activity.

14.
Mol Ther Oncolytics ; 22: 565-573, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34553041

RESUMO

Endostatin (ES, ENDO) has been reported to suppress the growth of tumors while inducing the proliferation of lung cancer stem cells (LCSCs), causing a poor prognosis for lung cancer. In this study, we aimed to clarify whether BRM270 can inhibit the proliferation of cancer stem cells (CSCs). Endostatin + BRM270 showed anti-tumor effects by reducing tumor volume and increasing survival. Administration of BRM270 reduced the number of aldehyde dehydrogenase-positive (ALDH+) cells and the level of ALDH1A1 expression in tumors by increasing the level of miR-128 while decreasing the levels of BMI-1, ABCC-5, E2F3, and c-MET. The luciferase activity of miR-128 promoter was increased by an increasing concentration of BRM270. In addition, BMI-1, ABCC-5, E2F3, and c-MET were identified as candidate targets of miR-128, and the overexpression of miR-128 significantly reduced mRNA/protein levels of BMI-1, ABCC-5, E2F3, and c-MET in A549 and H460 cells. Administration of BRM270 inhibited the expression of BMI-1, ABCC-5, E2F3, and c-MET in a dose-dependent manner. In this study, we showed for the first time that the combined administration of endostatin and BRM270 achieved anti-tumor effects while suppressing the proliferation of stem cells.

15.
Front Immunol ; 12: 691908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589082

RESUMO

Decidual macrophages (dMϕ) are the second largest population of leukocytes at the maternal-fetal interface and play critical roles in maintaining pregnancy. Our previous studies demonstrated the active involvement of monoclonal nonspecific suppressor factor-ß (MNSFß) in embryonic implantation and pregnancy success. MNSFß is a ubiquitously expressed ubiquitin-like protein that also exhibits immune regulatory potential, but its function in human dMϕ remains unknown. Here, we observed that the proportion of CD11chigh (CD11cHI) dMϕ was significantly increased in dMϕ derived from patients with recurrent pregnancy loss (RPL dMϕ) compared to those derived from normal pregnant women (Control dMϕ). The production of MNSFß and TNFα by RPL dMϕ was also significantly increased compared to that by Control dMϕ. Conditioned medium from RPL dMϕ exerted an inhibitory effect on the invasiveness of human trophoblastic HTR8/SVneo cells, and this effect could be partially reversed by a neutralizing antibody against TNFα. Bioinformatics analysis indicated a potential interaction between MNSFß and RC3H1, a suppressor of TNFα transcription. Immunoprecipitation experiments with human Mϕ differentiated from the human monocyte cell line Thp1 (Thp1-derived Mϕ) proved the binding of MNSFß to RC3H1. Specific knockdown of MNSFß in Thp1-derived Mϕ led to a marked decrease in TNFα production, which could be reversed by inhibiting RC3H1 expression. Interestingly, a significant decrease in the protein level of RC3H1 was observed in RPL dMϕ. Together, our findings indicate that aberrantly increased MNSFß expression in dMϕ may promote TNFα production via its interaction with RC3H1, and these phenomena could result in the disruption of the immune balance at the maternal-fetal interface and thus pregnancy loss.


Assuntos
Aborto Habitual/imunologia , Decídua/imunologia , Macrófagos/imunologia , Proteínas de Ligação a RNA/imunologia , Fatores Supressores Imunológicos/imunologia , Fator de Necrose Tumoral alfa/imunologia , Ubiquitina-Proteína Ligases/imunologia , Adulto , Células Cultivadas , Feminino , Humanos , Gravidez , Fatores Supressores Imunológicos/genética
16.
Exp Ther Med ; 22(3): 1016, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373702

RESUMO

It has been reported that morphine pretreatment (MP) can exert neuroprotective effects, and that protein kinase C (PKC) participates in the initiation and development of ischemic/hypoxic preconditioning in the brain. However, it remains unknown whether PKC is involved in MP-induced neuroprotection. The aim of the present study, which included in vivo and in vitro experiments, was to determine whether the conventional γ isoform of PKC (cPKCγ) was involved in the protective effects of MP against cerebral ischemic injury. The present study included an in vivo experiment using a mouse model of middle cerebral artery occlusion and an in vitro experiment using neuroblastoma N2a cells with oxygen-glucose deprivation (OGD). Furthermore, a cPKCγ antagonist, Go6983, was used to determine the involvement of cPKCγ in the protective effects of MP against cerebral ischemic injury. In the in vivo experiment, neurological deficits, ischemic infarct volume, neural cell damage, apoptosis and caspase-3 activation were evaluated. In the in vitro experiment, flow cytometry was used to determine the activation of caspase-3 in N2a cells with OGD. It was found that MP protected against cerebral ischemic injury. However, intracerebroventricular injection of the cPKCγ antagonist before MP attenuated the neuroprotective effect of MP and increased the activation of cleaved caspase-3. These findings suggested that MP may provide protection against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.

17.
ACS Appl Mater Interfaces ; 13(31): 37142-37151, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34333965

RESUMO

The local coordination structure of metal atoms in single-atom catalysts (SACs) greatly influences their catalytic performance. And for most SACs, single metal atoms were anchored on carbon materials with N or C coordination. However, the rational design of oxygen-containing SACs and analyzing its structure-performance relationship remain challenging. Herein, we used amino-rich compounds to tailor the metatungstate and fix the W atoms and finally obtained the oxygen-containing W-SACs. The structural evolution of tungsten and its coordination atoms were tracked by electrospray ionization high-definition mass spectrometry. Furthermore, aberration-corrected transmission electron microscopy, X-ray absorption fine-structure spectroscopy, and first-principles calculation results revealed that different from the traditional SACs, the WO2N2 moiety (W coordinated with two O atoms and two N atoms) may be the favored structure for W species. This special structure promoted the energy transfer for enhancing singlet oxygen generation. This work presents an efficient way to prepare more high-efficiency SACs by atomic-scale tailoring and structural evolution tracking at the molecular level.

18.
Medicine (Baltimore) ; 100(30): e26547, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397686

RESUMO

ABSTRACT: The main purpose of this study was to investigate current state of constipation for lung cancer (LC) patients receiving platinum-based chemotherapy. The relationships between social demography, clinical variables, psychological status, and constipation were analyzed. In addition, quality of life (QoL) in LC patients with constipation was also analyzed. One hundred LC patients participated in this cross-sectional study. Under the guidance of the researchers, Functional Living Index-Emesis, Piper Fatigue Scale, Patient Health Questionnaire, Generalized Anxiety Disorder-7, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0), Pittsburgh Sleep Quality Index, General Well-being Scale, Social Support Rate Scale, General Self-Efficacy Scale, and other related questionnaires were completed. The result showed the symptom of constipation was observed in 41 (41%) LC patients. The occurrence and development of constipation were associated with gender, food intake, exercise, nausea, fatigue, anxiety, depression, sleep disorders, and happiness. The study also found patients with constipation had significant lower QoL scores, especially the score in the general state. Constipation was very common in LC patients undergoing platinum-based chemotherapy. Reduced food intake and fatigue were the independent factors. Constipation significantly affects the QoL of the patients. Therefore, more attention should be paid to the risk factors of constipation in LC patients undergoing platinum-based chemotherapy, the earlier intervention was done to these patients, the better to improve their QoL.


Assuntos
Constipação Intestinal/complicações , Platina/farmacologia , Qualidade de Vida/psicologia , Idoso , Constipação Intestinal/etiologia , Constipação Intestinal/psicologia , Estudos Transversais , Tratamento Farmacológico/métodos , Tratamento Farmacológico/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente/estatística & dados numéricos , Platina/uso terapêutico
19.
Hereditas ; 158(1): 32, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425910

RESUMO

BACKGROUND: Coarctation of the aorta (CoA) is a serious innate heart disease. Although surgery results are generally good, some complications such as recoarctation and aortic aneurysm or persistent hypertension were serious threats to patient's health. To better understand the pathology of CoA and its underlying molecular mechanism is particularly important for early diagnosis and preventing the occurrence of its complications. However, the mechanisms of CoA remain unclear, especially for infants. METHODS: RNA sequencing (RNA-seq) was used to identify the differentially expressed genes (DEGs) in vascular tissues of 12 patients with CoA and 10 normal participants form 3- to 34-month-old infants. The characteristic of DEGs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunochemical staining (IHC) in vessels of patients with CoA and normal infants. RESULTS: A total of 2491 DEGs with the false discovery rate less than 0.05(> 1.5-fold, P < 0.05 change) were identified, including 443 upregulated genes and 2048 downregulated genes. The Gene Ontology enrichment analysis showed that 26 out of the 2491 DEGs identified were associated with cardiovascular diseases. These 26 genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs) differentiation. Three DEGs, that is, CNN1 (calponin), α-actinin1 and myosin heavy chain 11 MYH11, were validated using qRT-PCR and Western blot analysis. In addition, immunochemical staining showed that calponin and MYH11 were highly expressed on the surface and in the deep layers of the thickened intima respectively. CONCLUSION: This study comprehensively characterized the CoA transcriptome. Migration of extracellular matrix (ECM) and smooth muscle cells (SMCs) to the subendothelial space may be the major characteristic of CoA in infants.

20.
Neoplasma ; 68(5): 1023-1032, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34427097

RESUMO

Lung cancer is one of the most common malignant neoplasms worldwide. CD24 is a marker of tumor stem cells that plays an important role in tumorigenesis. Hsp70 is an important molecular chaperone. However, the co-expression and interaction of CD24 and Hsp70, as well as the significance for the prognosis of lung cancer are still unclear. The expression levels of CD24 and Hsp70 were detected by immunohistochemistry and their correlation was analyzed. The expression levels of CD24 mRNA and protein were examined using qRT-PCR and western blotting in SPCA1, A549, H1975, and H1650 cell lines. A CD24-overexpressing cell model was established. The interaction between CD24 and Hsp70 was verified by co-immunoprecipitation and western blotting. CD24 and Hsp70 expression were significantly higher in lung cancer tissues than in adjacent tissues (CD24: p=0.008; Hsp70: p<0.001). CD24 protein expression showed a positive correlation with lymph node metastasis, TNM stage, and vascular cancer thrombus. Hsp70 protein expression showed a positive correlation with differentiation, lymph node metastasis, and TNM stage. CD24 and Hsp70 high expression were also correlated with poor survival. The positive co-expression rate of CD24 and Hsp70 in lung cancer tissues was 52.7% (49/93). CD24 and Hsp70 expression in lung cancer were positively correlated (r=0.368, p<0.001), and co-immunoprecipitation was verified that both endogenous and exogenous CD24 co-precipitated with Hsp70 directly or indirectly. When Hsp70 inhibitor VER15508 was added to A549 cells, Hsp70 and CD24 protein expression were significantly decreased. The present study demonstrated that CD24 and Hsp70 were highly expressed in lung cancer tissues, and associated with invasion, metastasis, and poor survival. Hsp70 may regulate CD24 expression. Co-expression of CD24 and Hsp70 may be a prognostic biomarker for lung cancer.


Assuntos
Antígeno CD24 , Proteínas de Choque Térmico HSP70/metabolismo , Neoplasias Pulmonares , Biomarcadores Tumorais/genética , Proteínas de Choque Térmico HSP70/genética , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico
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