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1.
J Clin Neurosci ; 92: 147-152, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34509242

RESUMO

OBJECTIVE: Carotid blister aneurysms remain a formidable surgical challenge with varied surgical options. There have been significant advancements in the endovascular management of these aneurysms with the introduction of flow diverters. The comparative risk profiles for different endovascular options compared to surgical management of these lesions is not completely understood. METHODS: The study is a comprehensive systematic review and meta-analysis on the treatment of carotid blood blister aneurysms. Pubmed searches were used to identify relevant articles and patient level data was extracted. Two and three group analyses were conducted comparing surgical and endovascular strategies and surgical, stent coil and flow diversion techniques respectively. Patient outcomes were graded on the modified Rankin Scale with a score of 2 or less defined as favorable. RESULTS: In total, 83 studies (41 and 42 studies on surgical and endovascular interventions, respectively) with 1119 patients met our inclusion criteria. A statistically significant difference (at the 5% level of significance) in the effect among three different interventions was not found (Q = 3.41, p = 0.1815) under the random-effect model. Our results did show summary proportions of favorable outcomes were higher in the stent coil (0.87, 95% CI: 0.79 - 0.94) and flow diversion (0.87, 95% CI: 0.75 - 0.96) than that of surgery (0.76, 95% CI: 0.71 - 0.83). CONCLUSIONS: Our results suggest a trend towards improved patient outcomes with endovascular techniques compared to surgical strategies but statistical significance was not achieved. We also found that endovascular techniques compare favorably. Increasing retreatments were found to negatively affect patient outcomes.

2.
J Colloid Interface Sci ; 606(Pt 2): 1435-1444, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34492478

RESUMO

Improving the selectivity of photocatalysis and reducing the generation of toxic by-products are the two key challenges for the development of highly efficient and stable photocatalysts. In this work, it was revealed that Zn-Ti-layered double hydroxide (ZT-LDH) photocatalyst, which generated less intermediates, showed better toluene degradation efficiency (removal ratio, 75.2%) and stability, compared with P25 (removal ratio, 10.9%). During the photocatalytic toluene degradation, benzaldehyde and benzoic acid were the main intermediates existed in the gas phase and on the surface of the catalyst, respectively. By combining experiments with theoretical calculation, it was found that the hydrogen atoms on the hydroxyl groups in the LDH would selectively attract the oxygen atoms in the carbon-oxygen double bond of the two major intermediates, facilitating their adsorption and activation on ZT-LDH. Besides, the surface electronic structure of ZT-LDH was demonstrated to facilitate the ring-opening reaction of the two major intermediates, eventually maintaining high activity and stability. This work could provide new molecular perspectives for understanding the photocatalytic reactions in VOCs degradation and developing efficient and stable photocatalysts.

3.
J Hazard Mater ; 416: 125850, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492801

RESUMO

This study aims to unravel the microbial responses to Cr(VI) stress in anaerobic ammonium oxidation (anammox) reactor. The result showed that anammox process could tolerate 2 mg/L Cr(VI) after acclimation, while 5 mg/L Cr(VI) stress resulted in significant inhibition on anammox bacterial activity. Ca. Jettenia was the predominant anammox genus, whose abundance showed a decreasing tendency with increasing Cr(VI) dosage. Cr(VI) addition resulted in significant and irreversible changes in microbial community structure, and increased the relative influence of stochastic processes on community assembly. Furthermore, rare subcommunity contributed greatly to biodiversity of whole community (90.35%), while abundant subcommunity were more similar to the whole community. Importantly, Cr(VI) exposure caused greater variations in rare subcommunity compared with abundant one, indicating that rare taxa were more sensitive to Cr(VI) stress. This was further confirmed by ABT model, which showed higher relative influence of Cr(VI) on rare subcommunity. In addition, results suggested that rare taxa play essential roles in whole community stability, because of their great contribution to species richness and community variations, and keystone roles in ecosystem network. Moreover, network analysis showed that conditionally rare taxa frequently and positively interacted with abundant taxa, which may contribute to the community resilience to Cr(VI) stress.


Assuntos
Cromo , Microbiota , Bactérias/genética , Biodiversidade , Cromo/toxicidade , Oxirredução
4.
Ecotoxicol Environ Saf ; 225: 112717, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34478981

RESUMO

Due to the prohibition of polybrominated diphenyl ethers, organophosphate flame retardants (OPFRs) and tetrabromobisphenol A (TBBPA) have become emerging flame retardants. However, knowledge about their occurrence, especially their transformation products, is still limited. This study collected sediment samples from two rivers, i.e., Lianjiang River (located at an e-waste dismantling area) and Xiaoqing River (situated at a flame retardant production base), to investigate the occurrence, composition, and spatiality distribution of OPFRs, TBBPA, and their transformation products. Both targets were detected in the Lianjiang River in the range of 220-1.4 × 104 and 108-3.1 × 103 ng/g dw (dry weight) for OPFRs and TBBPA, and 0.11-2.35 and 4.8-414 ng/g dw for their respective transformation products, respectively. The concentrations of OPFRs and TBBPA in the Xiaoqing River ranged from 4.15 to 31.5 and 0.76-2.51 ng/g dw, respectively, and no transformation products were detected. Different compositional characteristics of OPFRs and distinct spatial distribution from mainstream and tributary observed between the two rivers are attributed to the difference in the local industries. Spatial distribution and principal component analysis indicated that e-waste dismantling activities could be a vital source of local pollution. Besides, the confluence of tributaries seemed to determine the contaminant levels in the Xiaoqing River. Also, concentration ratios and Spearman's correlation between metabolites and parent chemicals were analyzed. Low concentration ratios (3.6 ×10-4 to 0.16) indicated a low transformation degree, and Spearman's correlation analysis suggested transformation products were partly stemming from commercial products. Considering the limited study of these transformation products, more studies on their sources, transform mechanism, and toxicity are required.

5.
Mol Med Rep ; 24(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34515321

RESUMO

Bladder cancer has high morbidity and mortality rates among the male genitourinary system tumor types. MicroRNA­218 (miR­218) is associated with the development of a variety of cancer types, including bladder cancer. Rab6c is a member of the Rab family and is involved in drug resistance in MCF7 cells. The aim of the present study was to clarify the relationship between Rab6c and miR­218 in bladder cancer cell lines. In this study, the expression levels of miR­218 and Rab6c were evaluated via reverse transcription­quantitative PCR and western blotting, respectively. The association between Rab6c and miR­218 was recognized via TargetScan analysis and dual luciferase reporter gene detection. Cell proliferation was analyzed using Cell Counting Kit­8 and colony formation assays, and the invasive ability was measured via Transwell assays. Rab6c was highly expressed in bladder cancer, while miR­218 had abnormally low expression in bladder cancer. In addition, there was a mutual regulation between Rab6c and miR­218 in bladder cancer. It was found that overexpression of Rab6c significantly enhanced the proliferation, colony formation and invasion of T24 and EJ cells. Furthermore, miR­218 overexpression blocked the promoting effects of Rab6c on the malignant behavior of bladder cancer cells. Thus, Rab6c promotes the proliferation and invasion of bladder cancer cells, while miR­218 has the opposite effect, which may provide a novel insight for the treatment of bladder cancer.

6.
Biomed Res Int ; 2021: 9983725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471643

RESUMO

Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.

7.
ACS Nano ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469113

RESUMO

The synergy between metal alloy nanoparticles (NPs) and single atoms (SAs) should maximize the catalytic activity. However, there are no relevant reports on photocatalytic CO2 reduction via utilizing the synergy between SAs and alloy NPs. Herein, we developed a facile photodeposition method to coload the Cu SAs and Au-Cu alloy NPs on TiO2 for the photocatalytic synthesis of solar fuels with CO2 and H2O. The optimized photocatalyst achieved record-high performance with formation rates of 3578.9 for CH4 and 369.8 µmol g-1 h-1 for C2H4, making it significantly more realistic to implement sunlight-driven synthesis of value-added solar fuels. The combined in situ FT-IR spectra and DFT calculations revealed the molecular mechanisms of photocatalytic CO2 reduction and C-C coupling to form C2H4. We proposed that the synergistic function of Cu SAs and Au-Cu alloy NPs could enhance the adsorption activation of CO2 and H2O and lower the overall activation energy barrier (including the rate-determining step) for the CH4 and C2H4 formation. These factors all enable highly efficient and stable production of solar fuels of CH4 and C2H4. The concept of synergistic SAs and metal alloys cocatalysts can be extended to other systems, thus contributing to the development of more effective cocatalysts.

8.
Biochem Biophys Res Commun ; 577: 130-138, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34517210

RESUMO

Gliomas are the major type of primary brain tumors. Accumulating research has demonstrated that tubulin is connected with the development and malignant progression of tumors. TUBA1C is a subtype of α-tubulin and is linked to prognosis in multiple cancers. In this study, the prognosis-related gene TUBA1C in glioma was identified and analyzed by bioinformatic approaches such as Kaplan-Meier (KM) survival time analysis, univariate and multivariate Cox analysis, receiver operating characteristic (ROC) analysis and functional enrichment analysis. Based on the above analyses, we found that glioma tissues had significantly higher expression of TUBA1C than normal brain tissues, and high expression of TUBA1C has worse prognosis in glioma. Gene set enrichment analysis (GSEA) revealed the signaling pathways related to the cell cycle. Furthermore, knockdown of TUBA1C also inhibited proliferation and migration and caused apoptosis and G2/M phase arrest in glioma cells. This study demonstrated that high TUBA1C expression correlated with poor outcomes in glioma patients and that knocking down TUBA1C suppressed glioma cell proliferation via cell cycle arrest. In addition, TUBA1C might be a therapeutic biomarker for gliomas.

9.
Sci Total Environ ; 804: 150153, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34509835

RESUMO

Pyrene, a typical four-ring polycyclic aromatic hydrocarbon, is abundantly present in the environment and is potentially harmful to the human body. In this study, single-chamber air-cathode microbial fuel cells (MFCs) were used to treat pyrene, and the ensuing degradation, electrical parameters, and microbial changes were analyzed. The results showed that MFCs could degrade pyrene, and the maximum degradation rate for 30 mg/L reached 88.1 ± 5.4%. The addition of pyrene reduced the electrical performance of the MFCs and suppressed the power output. Analysis of the anodic microbial community showed that the proportion of Alcaligenes and Stenotrophomonas increased with an increase in pyrene concentration, which may explain the high degradation rate of pyrene.

10.
Acta Neuropathol ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536123

RESUMO

Since the discovery of ketamine anti-depressant effects in last decade, it has effectively revitalized interest in investigating excitatory synapses hypothesis in the pathogenesis of depression. In the present study, we aimed to reveal the excitatory synaptic regulation of corticotropin-releasing hormone (CRH) neuron in the hypothalamus, which is the driving force in hypothalamic-pituitary-adrenal (HPA) axis regulation. This study constitutes the first observation of an increased density of PSD-93-CRH co-localized neurons in the hypothalamic paraventricular nucleus (PVN) of patients with major depression. PSD-93 overexpression in CRH neurons in the PVN induced depression-like behaviors in mice, accompanied by increased serum corticosterone level. PSD-93 knockdown relieved the depression-like phenotypes in a lipopolysaccharide (LPS)-induced depression model. Electrophysiological data showed that PSD-93 overexpression increased CRH neurons synaptic activity, while PSD-93 knockdown decreased CRH neurons synaptic activity. Furthermore, we found that LPS induced increased the release of glutamate from microglia to CRH neurons resulted in depression-like behaviors using fiber photometry recordings. Together, these results show that PSD-93 is involved in the pathogenesis of depression via increasing the synaptic activity of CRH neurons in the PVN, leading to the hyperactivity of the HPA axis that underlies depression-like behaviors.

11.
Heart Rhythm ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481982

RESUMO

BACKGROUND: Exercise stress testing is frequently used to expose cardiac arrhythmias. Aerobic exercise conditioning has been used as a nonpharmacologic antiarrhythmic intervention. OBJECTIVE: To test the hypothesis that non-invasively recorded skin sympathetic nerve activity (SKNA) is increased during exercise and that SKNA response varies according to fitness levels. METHODS: Oxygen consumption (VO2) and SKNA were recorded in 39 patients undergoing an incremental exercise test. Patients were grouped by 5 levels of fitness based on age, sex and VO2max. RESULTS: With exercise, all patients had a significant increase in aSKNA (1.58±1.12 µV to 4.50±3.06 µV, p=0.000) and HR (87.40±20.42 bmp to 154.13±16.82 bmp, p=0.000). A mixed linear model of average SKNA (aSKNA) was used with fixed effects fitness, exercise time, recovery time and random effects of subject level intercept, slopes for exercise time and recovery times. The Poor fitness group had significantly higher average SKNA (aSKNA) than the others (p=0.0273). For all subjects studied, the aSKNA increased by 5% per min with the progression of exercise and decreased by 15% per min with the progression of recovery. The fitness variable encodes information on both comorbidities and BMI. Once fitness level is known, the comorbidities and BMI are not significantly associated with aSKNA. In all groups, aSKNA positively correlated with HR (R2=0.47±0.23) and VO2 (R2=0.68±0.25). CONCLUSION: The fitness level determines the magnitude and time course of SKNA increase during exercise. SKNA may be a useful fitness biomarker in exercise stress testing.

12.
World Neurosurg ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34547527

RESUMO

OBJECTIVE: Improving the gross total resection (GTR) rate of suprasellar pituitary macroadenomas (SPMAs) using the pure endoscopic endonasal transsphenoidal approach (EETA) has been a long-standing focus of neurosurgeons. This study was aimed at evaluating the influences of the removal of the tuberculum sellae bone (TSB) without opening the dura of the tuberculum sellae (TS) on the GTR rate of SPMAs via the EETA. METHODS: We retrospectively analyzed medical reports of patients with SPMAs who underwent the EETA between February 2015 and November 2020. Data on clinical manifestations, endocrinological types, imaging features (Hardy classification, morphology, and texture), clinical outcomes, and TSB removal status were collected. All patients were followed up for six months postoperatively. RESULTS: Seventy-eight patients were enrolled in our study. The GTR rates of the TSB removal group (45/78, 57.7%) and non-removal group (33/78, 42.3%) were 80.0% (36/45) and 57.6% (19/33), respectively. Univariate logistic regression analysis (LRA) found that the removal of TSB, rounded morphology, and low Hardy classification were correlated with higher GTR rates. Multiple LRA indicated that even after adjusting for tumor types and imaging features, the removal of TSB had an independent effect on the GTR rate (OR: 7.6, 95% CI: 1.8-31.6, P = 0.005). The incidence rates of postoperative cerebrospinal fluid (CSF) leakage and diabetes insipidus (DI) were not significantly different between the TSB removal group and TSB non-removal group. CONCLUSIONS: TSB removal using the EETA without opening the TS dura improves the GTR rate of SPMAs without increasing the incidence of postoperative complications.

13.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(8): 1125-1130, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34549701

RESUMO

OBJECTIVE: To explore the role of small nuclear noncoding RNA 7SK in embryonic stem cell (ESCs) proliferation and the value of 7SK as a target for early diagnosis and treatment for primordial dwarfism (PD). METHODS: ESC line R1 was transfected with the CRISPR/Cas9 system, and sequencing of the PCR product and glycerol gradient analysis were performed to identify novel 7SK deletion mutations. A lentivirus system was used to knock down cyclin-dependent kinase 9 (CDK9) in clones with 7SK deletion mutations, and the effect of CDK9 knockdown on the protein level of cell division cycle 6 (CDC6) was analyzed with Western blotting. RESULTS: We identified a novel deletion mutation of 7SK at 128-179 nt in the ESCs, which resulted in deficiency of cell proliferation. 7SK truncation at 128-179 nt significantly reduced the protein expressions of La-related protein 7 (LARP7) and CDC6. CONCLUSIONS: 7SK truncation at 128-179 nt can significantly impair proliferation of ESCs by downregulating CDC6. 7SK is a key regulator of proliferation and mediates the growth of ESCs through a mechanism dependent on CDK9 activity, suggesting the value of 7SK truncation at 128-179 nt as a potential target for early diagnosis and treatment of PD.

14.
Am J Pathol ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34390680

RESUMO

Aquaporins (AQPs) are normally expressed in the corneal epithelium. The aim of this study was to determine whether AQP5 played a role in corneal epithelial wound healing. AQP5 knockout (AQP5-/-) mice were constructed using CRISPR/Cas9 technology. A corneal wound healing model was performed using epithelial debridement on corneas. The time to corneal epithelial and nerve regeneration was significantly delayed in the AQP5-/- mice. Reduced Ki-67-positive cells and nerve growth factor (NGF) expression were confirmed in the AQP5-/- mice during healing. The epithelial and nerve regeneration rates were significantly promoted in the AQP5-/- mice by treatment with NGF, which was accompanied by recovered levels of phosphorylated Akt. NGF treatment also improved the recovery of corneal nerve fiber density and sensitivity in the AQP5-/- mice. However, the promotion of NGF induced corneal epithelial and nerve regeneration rates, and Akt reactivation was reversed by Akt inhibitor. The significant impairment of corneal wound healing in the AQP5-/- mice resulted from distinct defects in corneal epithelial cell proliferation and nerve regeneration. The results provided evidence for the involvement of aquaporin in cell proliferation and suggested that AQP5 induction could be a potential therapy for accelerating the resurfacing of corneal defects.

15.
Bioorg Chem ; 116: 105295, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34455300

RESUMO

We previously discovered extrahepatic cytochrome P450 1B1 (CYP1B1) degraders able to overcome drug resistance toward docetaxel using a PROTACs technology, however, the underexplored structure activity relationships and poor water solubility posed a major hurdle in the development of CYP1B1 degraders. Herein, continuous efforts are made to develop more promising α-naphthoflavone (ANF)-derived chimeras for degrading CYP1B1. Guided by the strongest ANF-derived CYP1B1 degrader 3a we ever reported, 17 ANF analogues are designed and synthesized to evaluate the CYP1B1 degradation and resultant resistance reversal. In degrading CYP1B1 and sensitizing drug resistance, 4d with a 1, 5-cis triazole coupling mode at (C3') of B ring of ANF exhibited the similar potency as 3a carrying a 1, 4-trans triazole fragment at (C4') of B ring, but more obvious selectivity of 4d toward CYP1B1 over CYP1A2 is observed. When an oxygen was inserted into the linker of 4d, 4f demonstrated better water solubility, a more potent ability in degrading CYP1B1 and reversing drug resistance, and a promising selectivity. Collectively, a substitution position, an alkyne-azide cyclization and a liker type significantly affect the ability of ANF-thalidomide conjugates in eliminating drug resistance of CYP1B1-expressing DU145 (DU145/CY) cells to docetaxel via targeted CYP1B1 degradation.

16.
Bioengineered ; 12(1): 4946-4961, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34365894

RESUMO

The solute carrier family has been reported to play critical roles in the progression of several cancers; however, the relationship between solute carrier family 12 member 8 (SLC12A8) and bladder cancer (BC) has not been clearly confirmed. This study explores the prognostic value of SLC12A8 for BC and its correlation with immune cell infiltration. We found that the expression of SLC12A8 mRNA was significantly overexpressed in BC tissues compared with noncancerous tissues in multiple public databases, and the result was validated using real-time PCR and immunohistochemistry (IHC). The Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of SLC12A8 for BC. The high expression of SLC12A8 led to a shorter overall survival time and was an unfavorable prognostic biomarker for BC. The mechanisms of SLC12A8 promoting tumorigenesis were investigated by Gene Set Enrichment Analysis (GSEA). Moreover, the correlations of SLC12A8 expression with the tumor-infiltrating immune cells (TICs) in BC were explored using TIMER 2.0 and CIBERSORT. SLC12A8 was associated with CD4+ T cells, dendritic cells, neutrophils, and macrophages infiltration. The expression of SLC12A8 was positively correlated with crucial immune checkpoint molecules. In conclusion, SLC12A8 might be an unfavorable prognostic biomarker in BC related to tumor immune cell infiltration.

17.
Biomed Eng Online ; 20(1): 79, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362379

RESUMO

BACKGROUND: Anterior resection syndrome (ARS) is characterized by the diverse and interchangeable evacuatory symptoms that may occur following distal colorectal resection. We aimed to investigate the effect and potential mechanisms of ozone perfusion on rats with anterior rectal resection (ARR). MATERIAL AND METHODS: After establishment of rat ARR model, 20, 40 and 80 ug/ml ozone was used to treat rats by enema administration. The pathological examination of intestinal tissue was detected using hematoxylin-eosin staining. The rate of loose stools, minimum threshold volume of abdominal withdrawal reflex (AWR) and Bristol grade were used to evaluate the degree of abnormal defecation function. Subsequently, the levels of oxidative stress- and inflammation-related markers, 5-hydroxytryptamine (5-HT), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the serum and intestinal tissue were determined with the corresponding kits. Meanwhile, the expression of nuclear factor kappa B (NF-κB) p65, transient receptor potential vanilloid (TRPV)1, TRPV4, iNOS and 5-HT receptor 3A (5-HTR3A) was determined with RT-qPCR and western blotting. RESULTS: Ozone administration (20 and 40 ug/ml) significantly alleviated the pathological changes of intestinal tissue-induced by ARR, accompanied by the decreased loose stools rate, Bristol score and increased abdominal withdraw reflex. However, 80 ug/ml of ozone intervention played opposite roles in the aforementioned changes with 20 and 40 ug/ml of ozone. Additionally, remarkably elevated reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), 5-HT, iNOS and NO levels were observed in the ozone-treated groups (20 and 40 ug/ml), while high dose of ozone drastically improved ROS, MDA, 5-HT, iNOS and NO levels but reduced the activity of SOD. Consistently, the contents of inflammatory factors were decreased after low and middle doses of ozone administration. However, high dose of ozone aggravated the inflammatory injury. Moreover, 20 and 40 ug/ml ozone upregulated TRPV1 and TRPV4 expression but downregulated 5-HTR3A expression, which was restored after 80 ug/ml of ozone intervention. Remarkably, the levels of NF-κB p65 and iNOS were dose-dependently enhanced following ozone treatment. CONCLUSIONS: Taken together, low concentration of ozone attenuated intestinal injury induced by ARR via balancing oxidative stress and inflammation, but high concentration of ozone exacerbated the intestinal injury, which might be related to the 5-HT and TRPV signaling.

18.
Life Sci Alliance ; 4(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34429344

RESUMO

Sepsis is defined as an organ dysfunction syndrome and it has high mortality worldwide. This study analysed the proteome of serum from patients with sepsis to characterize the pathological mechanism and pathways involved in sepsis. A total of 59 patients with sepsis were enrolled for quantitative proteomic analysis. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network specific to sepsis. Key regulatory modules that were detected were highly correlated with sepsis patients and related to multiple functional groups, including plasma lipoprotein particle remodeling, inflammatory response, and wound healing. Complement activation was significantly associated with sepsis-associated encephalopathy. Triglyceride/cholesterol homeostasis was found to be related to sepsis-associated acute kidney injury. Twelve hub proteins were identified, which might be predictive biomarkers of sepsis. External validation of the hub proteins showed their significantly differential expression in sepsis patients. This study identified that plasma lipoprotein processes played a crucial role in sepsis patients, that complement activation contributed to sepsis-associated encephalopathy, and that triglyceride/cholesterol homeostasis was associated with sepsis-associated acute kidney injury.

19.
Pestic Biochem Physiol ; 178: 104923, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34446199

RESUMO

Cell division cycle protein 37 (Cdc37) is a molecular chaperone that actively participates in many intracellular physiological and biochemical processes as well as pathogen infection. However, the function of Cdc37 in silkworm cells under Bombyx mori nucleopolyhedrovirus (BmNPV) infection is unknown. We cloned and identified BmCdc37, a Cdc37 gene from B. mori, which is highly conserved among other species. After BmNPV infection, the expression level of the BmCdc37 gene was up-regulated and showed an expression pattern similar to the BmHsp90 gene, which relies on Cdc37 to stabilize and activate specific protein kinases. The immunofluorescence, bimolecular fluorescence complementation (BiFC), and co-immunoprecipitation (Co-IP) assays all indicated that BmCdc37 interacts with BmHsp90 in silkworm cells. Both BmCdc37 and BmHsp90 promote the reproduction of BmNPV. Co-expression of BmCdc37 and BmHsp90 was better at promoting virus proliferation than overexpression alone. These findings all indicate that BmCdc37 plays an active role in the proliferation of BmNPV.


Assuntos
Bombyx , Animais , Bombyx/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células , Interações Hospedeiro-Patógeno , Proteínas de Insetos/genética , Nucleopoliedrovírus
20.
Biomaterials ; 276: 121056, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34364178

RESUMO

Exosomes, endogenous nanosized particles (50-150 nm) secreted and absorbed by cells, have been recently used as diagnostic and therapeutic platforms in cancer treatment. The integration of exosome-based delivery with multiple therapeutic modalities could result in better clinical outcomes and reduced-sided effects. Here, we combined the targeting and biocompatibility of designer exosomes with chemo/gene/photothermal therapy. Our platform consists of exosomes loaded with internalized doxorubicin (DOX, a model cancer drug) and coated with magnetic nanoparticles conjugated with molecular beacons capable of targeting miR-21 for responsive molecular imaging. The coated magnetic nanoparticle enables enrichment of the exosomes at the tumor site by external magnetic field guidance. After the exosomes are gathered at the tumor site, the application of near-infrared radiation (NIR) induces localized hyperthermia and triggers the release of cargoes loaded inside the exosome. The released molecular beacon can target the miR-21 for both imaging and gene silencing. Meanwhile, the released doxorubicin serves to kill the cancer cells. About 91.04 % of cancer cells are killed after treatment with Exo-DOX-Fe3O4@PDA-MB under NIR. The ability of the exosome-based method for cancer therapy has been demonstrated by animal models, in which the tumor size is reduced dramatically by 97.57 % with a magnetic field-guided tumor-targeted chemo/gene/photothermal approach. Thus, we expected this designer exosome-mediated multi-mode therapy to be a promising platform for the next-generation precision cancer nanomedicines.


Assuntos
Exossomos , Hipertermia Induzida , Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , Polímeros
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