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1.
BMC Endocr Disord ; 21(1): 90, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933067

RESUMO

BACKGROUND: Hypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in individuals with multiple endocrine adenomatosis-1 (MEN-1). The rare occurrence of non-PTH-dependent hypercalcemia associated with acromegaly is attributable to complex factors involving increased intestinal calcium absorption, enhanced bone calcium release, and reduced urinary calcium elimination. Although patients with acromegaly often have mild hyperphosphatemia and hypercalciuria, clinically significant hypercalcemia is extremely rare. CASE PRESENTATION: Here we present a case of non-PTH-dependent hypercalcemia associated with a growth hormone- (GH) and prolactin- (PRL) co-secreting pituitary macroadenoma. A 37-year-old Chinese man presented with a 6-year history of increasing ring and shoe sizes and was referred to the West China Hospital of Sichuan University for treatment of acromegaly. Pituitary magnetic resonance imaging (MRI) showed a 2.0 × 1.7 × 1.9 cm macroadenoma. Laboratory examinations revealed high serum concentrations of GH and PRL with mild hypercalcemia, hyperphosphatemia, hypercalciuria, inhibited PTH concentration, and increased bone turnover markers. Administration of cabergoline together with somatostatin resulted in sharp decreases in his GH, PRL, and serum and urinary calcium concentrations. These values were further reduced 5 months later and his PTH and bone turnover markers gradually returned to within the normal range. CONCLUSIONS: Mild hyperphosphatemia and hypercalciuria are common in individuals with acromegaly and deserve attention because they may contribute to osteoporosis and urolithiasis. However, overt hypercalcemia is rare in such individuals. It is usually attributable to a coexisting parathyroid hyperplasia or adenoma, rarely being non-PTH-dependent. In such cases, the hypercalcemia is attributable to excessive PRL and hypogonadism and reverses with remission of acromegaly.

2.
Water Res ; 197: 117091, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33857896

RESUMO

Rapid achievement of nitritation of mainstream municipal wastewater in a continuous-flow process is attractive since it favors the involvement of the anammox process and reduces the operational costs. In this study, a feasible and economical strategy is proposed to rapidly achieve the nitritation of municipal wastewater. By aggressively discharging excess sludge during the seasonal warming period (temperature increasing from 18°C to 22°C), nitritation was established in 15 days with a nitrite accumulation ratio of 85.09% in a continuous-flow anaerobic/oxic (An/O) reactor. Meanwhile, qPCR results revealed that amoA abundance increased from (1.78±0.10) × 108 copies/(g VSS) to (1.05±0.11) × 1010 copies/(g VSS) while the abundance of nitrite-oxidizing bacteria decreased from (1.1±0.02) × 1010 copies/(g VSS) to (5.01±0.02) × 108 copies/(g VSS). The temperature gradually stabilized at 26°C during the following operational period and stable nitritation was maintained with a nitrite accumulation ratio above 90%, which was mainly attributed to a short sludge retention time (SRT) of 4.3 days and a low dissolved oxygen of 0.86 ± 0.5 mg/L. Falling temperature negatively impacted the stability of nitritation, but nitritation could be restarted by aggressively discharging excess sludge during another temperature increase period. Overall, this study provides a feasible strategy to start-up nitritation that has great potential applications for municipal wastewater treatment.


Assuntos
Compostos de Amônio , Esgotos , Anaerobiose , Reatores Biológicos , Nitritos , Nitrogênio , Oxirredução , Águas Residuárias
3.
Surg Endosc ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835250

RESUMO

BACKGROUND: The paracaval portion of the caudate lobe is located in the core of the liver. Lesions originating in the paracaval portion often cling to or even invade major hepatic vascular structures. The traditional open anterior hepatic transection approach has been adopted to treat paracaval-originating lesions. With the development of laparoscopic surgery, paracaval-originating lesions are no longer an absolute contraindication for laparoscopic liver resection. This study aimed to evaluate the safety and feasibility of laparoscopic anterior hepatic transection for resecting paracaval-originating lesions. METHODS: This study included 15 patients who underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection between August 2017 and April 2020. The perioperative indicators, follow-up results, operative techniques and surgical indications were retrospectively evaluated. RESULTS: All patients underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection. The median operation time was 305 min (220-740 min), the median intraoperative blood loss was 400 ml (250-3600 ml), and the median length of postoperative hospital stay was 9 days (5-20 days). No conversion to laparotomy or perioperative deaths occurred. Six patients had Clavien grade III-IV complications (III/IV, 5/1). Two patients developed tumor recurrence after 13 months and 8 months. CONCLUSION: Although technically challenging, laparoscopic anterior hepatic transection is still a safe and feasible procedure for resecting paracaval-originating lesions in select patients.

4.
Endocr J ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790062

RESUMO

Bilateral inferior petrosal sinus sampling (BIPSS) is the current gold standard test for differentially diagnosing ACTH-dependent Cushing's syndrome (CS). However, BIPSS is an invasive procedure, and its availability is limited. We retrospectively analysed the 24-hour urinary free cortisol (UFC) level during the high-dose dexamethasone suppression test (HDDST) and plasma ACTH/cortisol levels after the desmopressin stimulation test (DDAVP test) in subjects with confirmed Cushing's disease (CD) (n = 92) and ectopic ACTH-dependent CS (EAS) (n = 16), and evaluated the positive predictive value (PPV) of the two combined-tests in the aetiological diagnosis of ACTH-dependent CS. The percent changes in UFC levels after the HDDST and in ACTH/cortisol levels after DDAVP administration relative to the corresponding basal levels and the area under the receiver operating characteristic (ROC) curve (AUC) were analysed. UFC suppression below 62.7% suggested a pituitary origin with a sensitivity (SE) of 80% (95% CI: 70-88) and a specificity (SP) of 80% (95% CI: 52-96). A threshold increase in the ACTH level after DDAVP stimulation of 44.6% identified CD with an SE of 91% (95% CI: 83-97) and an SP of 75% (95% CI: 48-93). The combination of both tests yielded an SE of 95.5% and PPV of 98.4% for CD, and significantly improved the efficiency of the differential diagnosis between CD and EAS. These dual non-invasive endocrine tests may substantially reduce the need for BIPSS in the etiological investigation of ACTH-dependent CS.

5.
Adv Mater ; : e2007548, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797810

RESUMO

Owing to the development of aqueous rechargeable zinc-ion batteries (ZIBs), flexible ZIBs are deemed as potential candidates to power wearable electronics. ZIBs with solid-state polymer electrolytes can not only maintain additional load-bearing properties, but exhibit enhanced electrochemical properties by preventing dendrite formation and inhibiting cathode dissolution. Substantial efforts have been applied to polymer electrolytes by developing solid polymer electrolytes, hydrogel polymer electrolytes, and hybrid polymer electrolytes; however, the research of polymer electrolytes for ZIBs is still immature. Herein, the recent progress in polymer electrolytes is summarized by category for flexible ZIBs, especially hydrogel electrolytes, including their synthesis and characterization. Aiming to provide an insight from lab research to commercialization, the relevant challenges, device configurations, and life cycle analysis are consolidated. As flexible batteries, the majority of polymer electrolytes exploited so far only emphasizes the electrochemical performance but the mechanical behavior and interactions with the electrode materials have hardly been considered. Hence, strategies of combining softness and strength and the integration with electrodes are discussed for flexible ZIBs. A ranking index, combining both electrochemical and mechanical properties, is introduced. Future research directions are also covered to guide research toward the commercialization of flexible ZIBs.

6.
Biomed Pharmacother ; 137: 111388, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761607

RESUMO

This study was the first to investigate the synthesis of near-infrared light-sensitive NO prodrug [Mn(PaPy2Q)(NO)]ClO4, and detection the amount of NO released by the drug in different time and near infrared light (10 mW, 20 mW). It showed that with the increase of light power, the time required for the drug to release NO was shortened, and we selected 20 mW, 10 min as a follow-up study of light power and irradiation time while ensuring the near-infrared light did not affect tumor cells. The cells were irradiated with 20 mW of near-infrared light for 10 min at 6 h after treatment with the drug on PC-3, LNCaP and 22RV1 cells, and NO concentration and cell survival rate were tested at 12 h, 24 h and 48 h. Experiments showed that NO concentration remained stable within 48 h and [Mn(PaPy2Q)(NO)]ClO4 inhibited the proliferation of cells in a concentration and time-dependent manner. Then we also found that [Mn(PaPy2Q)(NO)]ClO4 increased the expression of apoptosis-related proteins (PARP, Bax, Caspase 3/9), inhibited the expression of BCl-2 and increased the activity level of Caspase 3/7, which showed [Mn(PaPy2Q)(NO)]ClO4 promoted prostate cancer cells apoptosis. Next, the results in xenograft mouse model showed that [Mn(PaPy2Q)(NO)]ClO4 also had anti-prostate cancer effects in vivo, and the NO concentration increased in the tumor after near-infrared light irradiation. After [Mn(PaPy2Q)(NO)]ClO4 treatment 6 weeks, tumor volume was significantly reduced, Ki67 and BrdU protein expression was significantly reduced. TUNEL assay results showed that [Mn(PaPy2Q)(NO)]ClO4 could promote the apoptosis of solid tumors in vivo and in a concentration-dependent manner.

7.
ACS Appl Mater Interfaces ; 13(12): 14718-14727, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33728892

RESUMO

Metals were for decades perceived as devoid of interesting optical properties that could be harnessed for optical components and devices. However, with the development of accurate nanofabrication techniques and precise control over architectural parameters, metals can be structured and characterized on the nanoscale. Metallic plasmonic nanomaterials exhibit a number of unique structural and optical properties, which offer the potential for developing new types of plasmonic devices. Here, we demonstrate a low-loss broadband polarizer based on a hybrid plasmonic fiber structure using metals as polarization-selective absorption materials. The polarization mechanism, design, fabrication, and characteristics of the plasmonic polarizers are investigated theoretically, numerically, and experimentally. The theoretical analysis predicts that the polarization-selective absorption with insensitivity to wavelength enables hybrid plasmonic fibers to function as broadband polarizers. Numerical simulations give the comparison of the polarization-selective absorption of various metallic nanomaterials (Ag, Au, In, Al, Cr) and show that aluminum is regarded as the optimum absorption material for the plasmonic polarizer. Experimental results show that through precise control over geometrical parameters, this device is capable of offering a high polarization extinction ratio (PER) of over 40 dB and a low insertion loss (IL) of less than 1.3 dB in the wavelength region of 810.1-870.0 nm. Compared with commercial birefringent-crystal-fiber polarizers, the plasmonic fiber polarizer has a better PER and IL bandwidth. These merits, combined with a compact and robust configuration, enable the plasmonic polarizer to have great potential in a broad range of applications.

8.
Nanomaterials (Basel) ; 11(3)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668165

RESUMO

Very recently, two new two-dimensional (2D) layered semi-conducting materials MoSi2N4 and WSi2N4 were successfully synthesized in experiments, and a large family of these two 2D materials, namely MA2Z4, was also predicted theoretically (Science, 369, 670 (2020)). Motivated by this exciting family, in this work, we systematically investigate the mechanical, electronic and optical properties of monolayer and bilayer MoSi2P4 and MoSi2As4 by using the first-principles calculation method. Numerical results indicate that both monolayer and bilayer MoSi2Z4 (Z = P, As) present good structural stability, isotropic mechanical parameters, moderate bandgap, favorable carrier mobilities, remarkable optical absorption, superior photon responsivity and external quantum efficiency. Especially, due to the wave-functions of band edges dominated by d orbital of the middle-layer Mo atoms are screened effectively, the bandgap and optical absorption hardly depend on the number of layers, providing an added convenience in the experimental fabrication of few-layer MoSi2Z4-based electronic and optoelectronic devices. We also build a monolayer MoSi2Z4-based 2D optoelectronic device, and quantitatively evaluate the photocurrent as a function of energy and polarization angle of the incident light. Our investigation verifies the excellent performance of a few-layer MoSi2Z4 and expands their potential application in nanoscale electronic and optoelectronic devices.

9.
Water Environ Res ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33539607

RESUMO

Aggregation of anammox bacteria is essential to maintain high biomass concentrations and prevent the loss of biomass in anammox processes. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used in this study to predict the metagenomic potentials and characterize the microbial community structure and functional features in anammox aggregates (e.g., sludge flocs, biofilms, and granules). The results showed that Candidatus Brocadia was the most dominant anammox genera in all aggregates (38.0% in flocs, 69.4% in biofilm, and 52.0% in granules) and the functional gene involved in the anammox process was detected in the highest amount in biofilms, followed by granules and flocs. Furthermore, the anammox microbial aggregation pathway was explored that anammox bacteria have strong motility and high capability for early attachment. Anammox bacteria could produce large amounts of EPS (extracellular polymeric substances) regulated by quinolone and transport to extracellular environment through type II secretion system. The strong ability of c-di-GMP (bis-(3'-5')-cyclic dimeric guanosine monophosphate) synthesis enabled a stable architectural structure of aggregation. This study elucidated the aggregation mechanism of anammox microorganisms at the genetic level to enhance the stability of anammox processes. PRACTITIONER POINTS: Candidatus Brocadia was the most dominant anammox genera in aggregates. Anammox bacteria have strong motility and high attachment capability. Anammox bacteria possess strong EPS synthesis regulated by quinolone. c-di-GMP synthesis enables a stable structure of aggregation.

12.
Surg Endosc ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625592

RESUMO

BACKGROUND: This retrospective 10-year case study evaluated the perioperative results and long-term efficacy of laparoscopic middle-hepatic-vein-guided hemihepatectomy (L-MHV-H) and traditional anatomical hemihepatectomy (TAH) in the treatment of hepatolithiasis (HL). METHODS: From January 2010 to December 2019, 99 patients with regional HL underwent laparoscopic anatomical hemihepatectomy (LAH) at our centre, including 43 patients in the L-MHV-H group and 56 patients in the TAH group. RESULTS: All patients in both groups were Child-Pugh grade A before operation. No significant between-group differences in general information, stone distribution, comorbidities, history of previous abdominal surgery or co-occurrence of gallstones and common bile duct stones were observed. The L-MHV-H group exhibited a higher intraoperative stone clearance rate (95.3% vs. 75.0%, p = 0.014) and a lower postoperative complication rate (10.1% vs. 48.2%, p = 0.005) compared with the TAH group. In the median follow-up time of 60 months (range 6-125 months), the L-MHV-H group had lower stone recurrence (2.3% vs. 19.6%, p = 0.013) and cholangitis recurrence (2.3% vs. 17.9%, p = 0.034) rates. No significant between-group differences in the other results were observed. CONCLUSIONS: L-MHV-H is safe and feasible for HL with certain advantages over TAH in improving the intraoperative stone clearance rate, reducing postoperative complication incidence and reducing stone and cholangitis recurrence rates.

13.
Small ; 17(13): e2007391, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33522108

RESUMO

Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide-lipid derivative (DSPE-PEG2000 -C6 -GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT-28nt (containing 17 guanines and 11 thymidines) and DSPE-PEG2000 -NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer-bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK-STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug-resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide-lipid derivative.

14.
Water Res ; 194: 116906, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609908

RESUMO

This study proposes a novel strategy of stably enriching anammox in mainstream, based on the competitive difference to NO2- between anoxic biofilms and suspended sludge. A modified anaerobic-anoxic-oxic (A2/O) process run for 500 days with actual municipal wastewater. Microbial analysis revealed that anoxic-carrier biofilms had a significantly higher abundance of anammox (qPCR: 0.74% - 4.34%) than suspended sludge (P< 0.001). Batch tests showed that anammox within anoxic-carrier biofilms contributed to significant nitrogen removal, coupled with partial-denitrification (NO3- â†’ NO2-). The anammox genus, Ca. Brocadia, was highly enriched when suspended sludge was accidentally lost. Further batch tests found that reducing suspended biomass helped anammox enrichment in anoxic-carrier biofilms, because the suspended sludge had strong NO2- competition (NO2- â†’ N2) with anammox (increased nirK). Metagenomic sequencing revealed that Ca. Brocadia dominates in the anoxic-carrier biofilms, and is the most important narG contributor to NO3- â†’ NO2-, which could have promoted the competition of NO2- with heterotrophic bacteria. For this A2/O process, the low effluent total nitrogen (8.9 mg ± 1.0 mg N/L) was attributed to partial-denitrification coupling with anammox, demonstrating that this process is applicable to the general influent N-concentration range (30 mg - 50 mg NH4+-N/L) of municipal wastewater treatment plants (WWTPs). Based on the special competitive preference of anammox for NO2-, this study provides a promising and practical alternative for enriching anammox bacteria in municipal WWTPs.


Assuntos
Desnitrificação , Esgotos , Anaerobiose , Biofilmes , Biomassa , Reatores Biológicos , Nitrogênio , Oxirredução , Águas Residuárias
15.
BMJ Open ; 11(2): e040718, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608398

RESUMO

INTRODUCTION: Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, to date, no prospective randomised study has adequately addressed whether initiating RRT earlier will attenuate renal injury and improve the outcome of sepsis. The objective of the trial is to compare the early strategy with delayed strategy on the outcomes in patients with SAKI in the intensive care unit (ICU). METHODS AND ANALYSIS: This is a large-scale, multicentre, randomised controlled trial about SAKI. In total, 460 patients with sepsis and evidence of AKI stage 2 of Kidney Disease Improving Global Outcomes (KDIGO) will be recruited and equally randomised into the early group and the delay group in a ratio of 1:1. In the early group, continuous RRT (CRRT) will be started immediately after randomisation. In the delay group, CRRT will initiated if at least one of the following criteria was met: stage 3 of KDIGO, severe hyperkalaemia, pulmonary oedema, blood urea nitrogen level higher than 112 mg/dL after randomisation. The primary outcome is overall survival in a 90-day follow-up period (90-day all-cause mortality). Other end points include 28-day, 60-day and 1-year mortality, recovery rate of renal function by day 28 and day 90, ICU and hospital length of stay, the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, the rate of complications potentially related to CRRT, CRRT-related cost, and concentrations of inflammatory mediators in serum. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2017-31-ks-01). Participants will be screened and enrolled from patients in the ICU with SAKI by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION: NCT03175328.


Assuntos
Lesão Renal Aguda , Terapia de Substituição Renal Contínua , Sepse , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Humanos , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Substituição Renal , Sepse/complicações , Sepse/terapia
16.
ACS Appl Mater Interfaces ; 13(8): 10480-10489, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33595295

RESUMO

We explore a series of Zn and N codoped TiO2 thin films grown using chemical vapor deposition. Films were prepared with various concentrations of Zn (0.4-2.9 at. % Zn vs Ti), and their impact on superoxide formation, photocatalytic activity, and bactericidal properties were determined. Superoxide (O2•-) formation was assessed using a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium sodium salt (XTT) as an indicator, photocatalytic activity was determined from the degradation of stearic acid under UVA light, and bactericidal activity was assessed using a Gram-negative bacterium E. coli under both UVA and fluorescent light (similar to what is found in a clinical environment). The 0.4% Zn,N:TiO2 thin film demonstrated the highest formal quantum efficiency in degrading stearic acid (3.3 × 10-5 molecules·photon-1), while the 1.0% Zn,N:TiO2 film showed the highest bactericidal activity under both UVA and fluorescent light conditions (>3 log kill). The enhanced efficiency of the films was correlated with increased charge carrier lifetime, supported by transient absorption spectroscopy (TAS) measurements.

17.
Curr Biol ; 31(5): 1084-1091.e4, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417880

RESUMO

The insect sex determination and the intimately linked dosage compensation pathways represent a challenging evolutionary puzzle that has been solved only in Drosophila melanogaster. Analyses of orthologs of the Drosophila genes identified in non-drosophilid taxa1,2 revealed that evolution of sex determination pathways is consistent with a bottom-up mode,3 where only the terminal genes within the pathway are well conserved. doublesex (dsx), occupying a bottom-most position and encoding sex-specific proteins orchestrating downstream sexual differentiation processes, is an ancient sex-determining gene present in all studied species.2,4,5 With the exception of lepidopterans, its female-specific splicing is known to be regulated by transformer (tra) and its co-factor transformer-2 (tra2).6-20 Here we show that in the African malaria mosquito Anopheles gambiae, a gene, which likely arose in the Anopheles lineage and which we call femaleless (fle), controls sex determination in females by regulating splicing of dsx and fruitless (fru; another terminal gene within a branch of the sex determination pathway). Moreover, fle represents a novel molecular link between the sex determination and dosage compensation pathways. It is necessary to suppress activation of dosage compensation in females, as demonstrated by the significant upregulation of the female X chromosome genes and a correlated female-specific lethality, but no negative effect on males, in response to fle knockdown. This unexpected property, combined with a high level of conservation in sequence and function in anopheline mosquitoes, makes fle an excellent target for genetic control of all major vectors of human malaria.

18.
Theranostics ; 11(3): 1429-1445, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391543

RESUMO

Rationale: Breast cancer preferentially develops osteolytic bone metastasis, which makes patients suffer from pain, fractures and spinal cord compression. Accumulating evidences have shown that exosomes play an irreplaceable role in pre-metastatic niche formation as a communication messenger. However, the function of exosomes secreted by breast cancer cells remains incompletely understood in bone metastasis of breast cancer. Methods: Mouse xenograft models and intravenous injection of exosomes were applied for analyzing the role of breast cancer cell-derived exosomes in vivo. Effects of exosomes secreted by the mildly metastatic MDA231 and its subline SCP28 with highly metastatic ability on osteoclasts formation were confirmed by TRAP staining, ELISA, microcomputed tomography, histomorphometric analyses, and pit formation assay. The candidate exosomal miRNAs for promoting osteoclastogenesis were globally screened by RNA-seq. qRT-PCR, western blot, confocal microscopy, and RNA interfering were performed to validate the function of exosomal miRNA. Results: Implantation of SCP28 tumor cells in situ leads to increased osteoclast activity and reduced bone density, which contributes to the formation of pre-metastatic niche for tumor cells. We found SCP28 cells-secreted exosomes are critical factors in promoting osteoclast differentiation and activation, which consequently accelerates bone lesion to reconstruct microenvironment for bone metastasis. Mechanistically, exosomal miR-21 derived from SCP28 cells facilitates osteoclastogenesis through regulating PDCD4 protein levels. Moreover, miR-21 level in serum exosomes of breast cancer patients with bone metastasis is significantly higher than that in other subpopulations. Conclusion: Our results indicate that breast cancer cell-derived exosomes play an important role in promoting breast cancer bone metastasis, which is associated with the formation of pre-metastatic niche via transferring miR-21 to osteoclasts. The data from patient samples further reflect the significance of miR-21 as a potential target for clinical diagnosis and treatment of breast cancer bone metastasis.

19.
Environ Sci Pollut Res Int ; 28(20): 25542-25551, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33462686

RESUMO

Several studies have previously reported that nanomaterial uptake and toxicity in plants are species dependent. However, the differences between photosynthetic pathways, C3 and C4, following nanomaterial exposure are poorly understood. In the current work, wheat and rice, two C3 pathway species are compared to amaranth and maize, which utilize the C4 photosynthetic mechanism. These plants were cultured in soils which were spiked with CuO, Ag, TiO2, MWCNT, and FLG nanomaterials. Overall, the C4 plant exhibited higher resilience to NM stress than C3 plants. In particular, significant differences were observed in chlorophyll contents with rice returning a 40.9-54.2% decrease compared to 3.5-15.1% for maize. Fv/Fm levels were significantly reduced by up to 51% in rice whereas no significant reductions were observed in amaranth and maize. Furthermore, NM uptake in the C3 species was greater than that in C4 plants, a trend that was also seen in metal concentration. TEM results showed that CuO NPs altered the chloroplast thylakoid structure in rice leaves and a large number of CuO NPs were observed in the vascular sheath cells. In contrast, there were no significant changes in the chloroplasts in the vascular sheath and no significant CuO NPs were found in maize leaves. This study was the first to systematically characterize the effect of metal and carbon-based nanomaterials in soil on C3 and C4 plants, providing a new perspective for understanding the impact of nanomaterials on plants.


Assuntos
Nanoestruturas , Oryza , Cloroplastos/metabolismo , Fotossíntese , Folhas de Planta , Zea mays
20.
Hum Exp Toxicol ; 40(6): 994-1002, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33307823

RESUMO

The inflammation and immune responses are critical in ischemic stroke and contribute to aggravated brain damage. Ephedrine was reported to play an important role in the control of inflammatory responses. This study was to investigate the repairing effects and potential mechanisms of ephedrine on cerebral ischemic injury in a rat model of focal cerebral ischemia. The rat model of cerebral ischemia/reperfusion injury was established using the middle cerebral artery occlusion (MCAO) method and then rats were treated with ephedrine (5 and 10 mg/kg) for 7 days. The neurobehavioral progression was assessed using the neurological scoring method. The pathology of brain tissue was evaluated by hematoxylin and eosin (H&E) staining. The infarct volume was examined by triphenyltetrazolium chloride (TTC) staining. The apoptosis in ischemic brain tissues was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Gene quantification and protein expression were detected by real-time PCR and western blot, respectively. Ephedrine treatment significantly alleviated the cerebral ischemia/reperfusion injury, evidenced by decreased neurological deficit score, infarct volume and water content. Ephedrine also decreased autophagy and apoptosis in brain tissues. Moreover, ephedrine treatment significantly reduced inflammatory responses, associating with decreasing the protein expression of p-NF-κB. These results demonstrated neuroprotective properties of ephedrine and highlighted it as a new potential anti-inflammatory agent against injury of cerebral ischemia/reperfusion.

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