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1.
Asian J Androl ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34259200

RESUMO

Benign prostatic hyperplasia (BPH) is a common disease in elderly men, and transurethral laser prostatectomy (TULP) has been widely used in the clinic to remove bladder outlet obstruction caused by BPH. Previous animal models for wound repair after prostatectomy have many limitations, and there have been no previous reports of a mouse model of TULP. Therefore, this study aimed to establish a novel mouse model of TULP. Twelve healthy adult Kunming (KM) mice received transurethral laser vaporization prostatectomy with a 200-µm thulium laser. The mice were sacrificed, and wound specimens from the prostatic urethra and bladder neck were harvested at 1 day, 3 days, 5 days, and 7 days after surgery. Hematoxylin-eosin (HE) and immunohistochemistry were applied to confirm the establishment of the mouse TULP model. One day after the surgery, urothelium expressing uroplakin (UPK) was absent in the urethral wound site, and a large number of necrotic tissues were found in the wound site. There was no UPK-positive urothelium in the wound 3 days after surgery. At 5 days after surgery, monolayer urothelium expressing UPK was found in the wound site, indicating that the re-epithelization of the wound had been completed. On the 7th day after surgery, there were multiple layers of urothelium with UPK expression, indicating that the repair was completed. It is feasible to establish a mouse TULP model by using a microcystoscope system and a 200-µm thulium laser.

2.
Biomater Sci ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34259244

RESUMO

Pathological angiogenesis is a critical contributor to atherosclerotic plaque rupture. However, there are few effective theranostic strategies to stabilize plaques by suppressing neovascularization. In this study, we fabricated a polymeric nanosystem using 3 nm manganese ferrite (MnFe2O4) and perfluorohexane (PFH) stabilized by polylactic acid-glycolic acid (PLGA) shells and conjugated to the surface of an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody [ramucirumab (Ram)]. The PFH@PLGA/MnFe2O4-Ram nanoparticles (NPs) were used as atherosclerotic plaque angiogenesis theranostics for multimodal imaging-guided photothermal therapy (PTT). Three-nanometer MnFe2O4 is an excellent magnetic resonance imaging T1 and photoacoustic imaging contrast agent. Upon exposure to near-infrared (NIR) light, MnFe2O4 in the NPs could transform NIR light into thermal energy for the photothermal elimination of plaque angiogenesis. Additionally, optical droplet vaporization of PFH in the NPs triggered by the thermal effect to form gas bubbles enhanced ultrasound imaging. Our in vitro experiments revealed that PFH@PLGA/MnFe2O4-Ram NPs actively accumulated in rabbit aortic endothelial cells, and NP-mediated PTT promoted endothelial cell apoptosis while inhibiting their proliferation, migration, and tubulogenesis. Notably, the PFH@PLGA/MnFe2O4-Ram NPs possessed excellent photostability and biocompatibility. In the rabbit advanced atherosclerotic plaque model, PFH@PLGA/MnFe2O4-Ram NP-guided PTT significantly induced apoptosis of neovascular endothelial cells and improved the hypoxia status in the plaque 3 days after treatment. On day 28, PTT significantly reduced the density of neovessels and subsequently stabilized rabbit plaques by inhibiting plaque hemorrhage and macrophage infiltration. Collectively, these results suggest that PFH@PLGA/MnFe2O4-Ram NP-guided PTT is a safe and effective theranostic strategy for inhibiting atherosclerotic plaque angiogenesis.

3.
Cancer Biol Med ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259423

RESUMO

OBJECTIVE: To study the efficacy of the enhanced recovery after surgery (ERAS) program on postoperative recovery and complications in patients with gastric cancer. METHODS: Eighty patients in the perioperative period with radical gastrectomy were enrolled and randomly divided into 2 groups, the ERAS group and the non-ERAS group. The differences between the 2 groups in terms of postoperative recoveries and complications rate were determined. According to the body mass index (BMI) level, the ERAS group was divided into 2 subgroups, namely group A (BMI < 28 kg/m2, n = 16) and group B (BMI ≥ 28 kg/m2, n = 24). The non-ERAS group was also divided into group C (BMI < 28 kg/m2, n = 18) and group D (BMI ≥ 28 kg/m2, n = 22). The recovery and complications of each group were then determined. RESULTS: The postoperative length of stay and visual analogue scale pain score were less in the ERAS group than the non-ERAS group (P < 0.05). Time to first postoperative exhaustion, first postoperative defecation, returning leukocyte count to normal, and stopping intravenous nutrition were significantly shorter in the ERAS group (n = 40), compared to the non-ERAS group (n = 40, all P < 0.05). The incidence of postoperative lower extremity intramuscular venous thrombosis was significantly higher in group D than in group B (χ2 = 4.800, P = 0.028). In addition, the incidence of lower extremity intermuscular venous thrombosis and lung infection in group D was higher than those in other groups. CONCLUSIONS: The perioperative ERAS program was associated with faster recovery in patients undergoing radical gastrectomy. For patients with higher BMI (BMI ≥ 28 kg/m2), the use of the perioperative ERAS program was more advantageous.

4.
Anal Chem ; 93(27): 9531-9540, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34197088

RESUMO

Telomere length (TL) is a highly relevant biomarker for age-associated diseases and cancer, yet its clinical applications have been hindered by the inability of existing methods to rapidly measure the TL distribution and the percentage of chromosomes with critically short telomeres (CSTs, < 3 kb). Herein, we report the development of a high-throughput method to measure TL at the single-chromosome level. Metaphase chromosomes are isolated, hybridized with the Alexa Fluor 488-labeled telomeric peptide nucleic acid probe, and analyzed using a laboratory-built ultrasensitive nano-flow cytometer. The fluorescence intensity of individual chromosomes is converted to TL in kilobases upon external calibration. With an analysis rate of several thousand chromosomes per minute, a statistically robust TL distribution histogram is acquired in minutes, and the percentage of chromosomes with CSTs can be quickly assessed. By analyzing peripheral blood lymphocytes of 158 healthy donors, TL is found to shorten with age at a rate of 64 ± 3 bp/year and the percentage of chromosomes with CSTs increases with age at a rate of 0.32 ± 0.02%/year. Moreover, the data of 28 patients with chronic myeloid leukemia (CML) indicate that telomeres are significantly shorter at the time of diagnosis and the clinical phases of CML are closely associated with TL and the percentage of chromosomes with CSTs. This powerful tool could greatly deepen our understanding of telomere biology and improve the clinical utility of telomere biomarkers.

5.
J Phys Chem Lett ; : 6639-6647, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254802

RESUMO

Here, we report (C4H9)4NCuCl2 single crystals with a luminous intensity that remains largely the same after soaking in water for 24 h. (CH9)4NCuCl2 has a new type zero-dimensional framework, in which the isolated [CuCl2]- anions are wrapped by organic (C4H9)4N+ cations. As expected, (C4H9)4NCuCl2 shows a broad emission band at 508 nm with a photoluminescence quantum yield of approximately 82% at room temperature, stemming from self-trapped exciton (STE) emission. Temperature-dependent photoluminescence measurement reveals that there is an energy barrier ΔE (24.0 meV) between the intrinsic state and STE state, which leads to the increase in emission intensity with an increase in temperature (98-278 K), while the emission intensity begins to decrease when the temperature is higher than 278 K due to the effects of both thermal quenching and carrier scattering. Our findings provide a new idea for the design of lead-free anti-water stability metal halide materials.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34275080

RESUMO

As an emerging class of nitrogenous disinfection by-products, halonitromethanes have caused public health concerns owing to their high toxicity. More and more attention has been paid to the new materials and technologies for the removal of halonitromethanes. In this study, a novel material, nanoscale zero-valent iron (nZVI) supported on MIL-96 (nZVI@MIL-96) with favorable stability and reusability, was synthesized and applied to the adsorption-degradation of trichloronitromethane (TCNM) in the water. The results revealed that almost all the TCNM could be removed under 20 mg/L nZVI@MIL-96 dosage with a wide temperature range. The optimum mass ratio of nZVI to MIL-96 was 1:2, and the TCNM adsorption-degradation followed a pseudo-first-order model. The coexisting ions, such as SO42-, PO43-, and NO3-, with high concentration brought adverse effects on the removal of TCNM; however, the effects of Cl- and CO32- were insignificant. The concentrations of aluminum and iron ions in water were all within the standard value after adsorption with the nZVI@MIL-96. The degradation mechanism of TCNM by nZVI@MIL-96 included two steps, namely, adsorption and degradation, and methylamine was the terminal dechlorination and denitration products. In a word, the as-prepared nZVI@MIL-96 nanoparticles demonstrated the capabilities as a material of adsorption-degradation of TCNM in the water.

7.
Pak J Pharm Sci ; 34(2): 585-589, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34275833

RESUMO

This study aims to explore the mechanism of NSAID-related gastric ulcer treated by JIA WEI WU QI SAN. Clean-grade SD rats were randomly divided into four groups. Group A was assigned as the control group. Groups B, C and D were intragastrically administered with 2.5mg/kg of indomethacin solution QD after 48 hours. After 15 days of treatment, group B was administered with 0.9% sodium chloride, group C was given rabeprazole (2mg/kg), and group D was administered with JIA WEI WU QI SAN (2g/kg). Abdominal aorta sampling was performed, and gastric tissues were isolated on the 29th day. The protein expression of p-P38MAPK and COX-2 were detected by western blot, while the concentration of PGE2 and IL-1 were determined by ELISA. (1) The expression of IL-1ingroup B dramatically declined in group D (P<0.01). (2)The expression of PGE-2dramatically increased in group D(P<0.01). (3) The expression of COX-2 increased in group D (P<0.05). (4) The expression of p-P38MAPK decreased in group D (P<0.05). JIA WEI WU QI SAN has multiple functions, including the activation of the p-P38MAPK signaling pathway, which promote the activation of COX-2, induce the arachidonic acid to increase the level of PG, and decrease the concentration of IL-1, thereby inducing an inflammatory reaction, and promote gastric mucosa repair.

8.
Ann Palliat Med ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34263616

RESUMO

Surgical management of patients with comorbid long-term myasthenia gravis (MG) is particularly challenging and MG thus represents an independent risk factor for perioperative complications. However, few studies have reported on the perioperative assessment, prevention measures, and risks in MG patients undergoing major surgery, especially for anterior cervical spine surgery. We herein report the rare case of a 62-year-old man with a 20-year history of MG, who was admitted to our hospital with diagnosis of degenerative cervical spondylosis. He safely underwent anterior cervical corpectomy of C4, discectomy of C5-6, and fusion of C3-6. Intraoperative motor evoked potential was recorded to detect significant improvement after decompression. However, the patient suffered from progressive dysphagia, bucking, and hyperpyrexia 20 days after the initial operation. Imaging revealed titanium cage sliding and graft dislodgement. Secondary surgery was performed for posterior internal fixation from C2-7 and anterior revision from C3-6 after Halo-Vest traction, antibiotic treatment, and immunoglobulin therapy. He underwent a series of postoperative treatments, including cervicothoracolumbosacral orthosis, atomization inhalation, chest physiotherapy, antibiotics, and nutritional support. His condition improved markedly and he had no recurrence of symptoms during the 6-month follow-up. It is the rare reported case of anterior cervical spinal surgery in a patient with MG. This rare case indicates a relative contraindication to anterior-only approaches especially with multiple levels for MG patients with cervical spondylosis. Posterior approach, intraoperative monitoring, osteoporosis, postoperative strong brace protection, and supportive management should be considered for patients who were on large doses of steroids for long duration of time, given the lack of sufficient bone mineral density.

9.
Crit Rev Food Sci Nutr ; : 1-33, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251918

RESUMO

An increasing demand for natural food preservatives is raised by consumers. For Nordic berry species, abundance of phenolic compounds and potent activities of anti-oxidation and anti-bacteria enables a great potential as food preservatives. This review provides a systematic examination of current literature on phenolic profiles, anti-oxidative and anti-bacterial activities of various extracts of Nordic berry species, as well as the impact of various structure features of phenolics on the bioactivities. Special attention is placed on exploitation of leaves of berry species and pomaces after juice-pressing as side-streams of berry production and processing. The current progress and challenges in application of Nordic berry species as food preservatives are discussed. To fully explore the potential application of Nordic berry species in food industry and especially to valorize the side-streams of berry cultivation (leaves) and juice-pressing industry (pomaces), it is crucial to obtain extracts and fractions with targeted phenolic composition, which have high food preserving efficacy and minimal impact on sensory qualities of food products.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34283387

RESUMO

Situs inversus totalis (SIT) is an extremely uncommon congenital disease where the major organs of the body are transposed through the sagittal plane. Kartagener syndrome is a complication of SIT with immotility of bronchial cilia, bronchiectasis, and chronic sinusitis. There is no report describing patients with Kartagener syndrome who accept uni-portal segmentectomies for lung cancer in past studies. Here we report a 74-year-old female patient with both Kartagener syndrome and a small early-stage lung cancer lesion located in the apical segment of the left upper lobe (LS1). The pulmonary segment anatomy of the left upper lobe in this case, which had very rare variants, was presented and interpreted in detail. This patient underwent an anatomic segmentectomy to the LS1 and a partial excision to the left middle lobe with bronchiectasis through a single 3 cm length incision. We believe that the case can give surgeons some experience and inspiration.

11.
Sci Data ; 8(1): 187, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285240

RESUMO

Real-time magnetic resonance imaging (RT-MRI) of human speech production is enabling significant advances in speech science, linguistics, bio-inspired speech technology development, and clinical applications. Easy access to RT-MRI is however limited, and comprehensive datasets with broad access are needed to catalyze research across numerous domains. The imaging of the rapidly moving articulators and dynamic airway shaping during speech demands high spatio-temporal resolution and robust reconstruction methods. Further, while reconstructed images have been published, to-date there is no open dataset providing raw multi-coil RT-MRI data from an optimized speech production experimental setup. Such datasets could enable new and improved methods for dynamic image reconstruction, artifact correction, feature extraction, and direct extraction of linguistically-relevant biomarkers. The present dataset offers a unique corpus of 2D sagittal-view RT-MRI videos along with synchronized audio for 75 participants performing linguistically motivated speech tasks, alongside the corresponding public domain raw RT-MRI data. The dataset also includes 3D volumetric vocal tract MRI during sustained speech sounds and high-resolution static anatomical T2-weighted upper airway MRI for each participant.

12.
Artif Cells Nanomed Biotechnol ; 49(1): 483-492, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34151664

RESUMO

Oxidative stress has been proven to play a critical role in the pathogenesis of neuronal injury. As a novel adipocytokine, omentin is produced by visceral adipose with insulin sensitizing effects and has been revealed to possess anti-inflammatory effects. However, the possible effect of omentin on oxidative stress remains unknown. The present study aimed to detect the potential protective effect of omentin against hydrogen peroxide (H2O2)-induced cytotoxicity of PC12 cells. The results showed that no cytotoxic effect was shown in PC12 cells co-cultured with omentin alone at a concentration of 50-1000 ng/mL. The CCK8 and TUNEL assays suggested that omentin could remarkably attenuate apoptosis induced by 100 µM H2O2. The PCR and western blotting showed that the expression levels of Bax was significantly inhibited by omentin via the upregulation of miR-128-3p at its 3'-UTR. Taken together, these results indicated that omentin protects PC12 cells against H2O2-induced apoptosis, and further studies need to be conducted before utilization in the clinic for the treatment of neurodegenerative diseases.

13.
Eur J Pharmacol ; 907: 174236, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34116043

RESUMO

Ischemia reperfusion injury (IRI) is associated with poor prognoses in the setting of ischemic brain diseases. Silence information regulator 1 (SIRT1) is a member of the third class of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins. Recently, the role of SIRT1/peroxisome proliferators-activated receptor-γ coactivator 1α (PGC-1α) pathway in organ (especially the brain) protection under various pathological conditions has been widely investigated. Mangiferin (MGF), a natural C-glucosyl xanthone polyhydroxy polyphenol, has been shown to be beneficial to several nervous system diseases and the protective effects of MGF can be achieved through the regulation of SIRT1 signaling. This study is designed to investigate the protective effects of MGF treatment in the setting of cerebral IRI and to elucidate the potential mechanisms. We first evaluated the toxicity of MGF and chose the safe concentrations for the following experiments. MGF exerted obvious neuroprotection against hypoxia/reoxygenation (HR)-induced injury, indicated by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release and reactive oxygen species generation. MGF also restored the protein expressions of SIRT1, PGC-1α, Nrf2, NQO1, HO-1, NRF1, UCP2, and Bcl2 down-regulated by HR treatment. However, SIRT1 siRNA could reverse MGF-induced neuroprotection and decrease the expressions of molecules mentioned above. Taken together, our findings suggest that MGF treatment exerts neuroprotection against HR injury via activating SIRT1/PGC-1α signaling. These findings may provide a theoretical basis for the exploitation of MGF as a potential neuroprotective drug candidate, which may be beneficial for the ischemic stroke patients in clinic.

14.
Ageing Res Rev ; 70: 101390, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34118443

RESUMO

Fibrosis is a typical aging-related pathological process involving almost all organs. It is usually initiated by organic injury and leads to the gradual decline of organ function or even loss. Circular RNAs (circRNAs) are being hailed as a newly rediscovered class of covalently closed transcripts without a 5' cap or 3' tail which draw increasing attention. In particular, circRNAs have been identified to be involved in the multifaceted processes of fibrosis in various organs, including the heart, liver, lung, and kidney. As more and more circRNAs are functionally characterized, they have become novel therapies for fibrosis. In this review, we systematically summarized current studies regarding the roles of circRNAs in fibrosis and shed light on the basis of circRNAs as a potential treatment for fibrosis.

15.
Lab Chip ; 21(14): 2684-2690, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34170274

RESUMO

An aqueous two-phase system (ATPS) is considered as a promising candidate for biological applications due to its excellent permeability, selective separation, rapid mass transfer and all-biocompatible nature. However, it remains difficult to generate ATPS emulsions with controllable and prolonged stability due to ultra-low interfacial tension. Here, we present a transient double emulsion (TDE) technique to address this challenge. The method involves two steps: (i) water-in-oil-in-water (W1/O/W2) transient double emulsion droplets are first produced with droplet microfluidics by introducing an additional middle oil phase, and (ii) the W1/O/W2 droplets dewet into oil-in-water and ATPS droplets in a controllable manner. Using the TDE method, both dextran-in-polyethylene glycol (PEG) and PEG-in-dextran ATPS droplets can be generated with high uniformity (coefficient of variation (CV) ranging from 0.66% to 2.55%), a wide range of droplet sizes (∼100 to 250 µm in radius), and tunability in the generation frequency (∼4 to 170 Hz). Tuning the oil viscosity controls the destabilization time for on-demand dewetting and releasing of aqueous core droplets. The stability of ATPS droplets is significantly improved by storing aqueous droplets in double emulsion vessels, which would benefit various applications, such as small molecule encapsulation.


Assuntos
Microfluídica , Água , Emulsões , Polietilenoglicóis , Viscosidade
16.
Int Immunopharmacol ; 98: 107846, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34174704

RESUMO

Patients with multiple sclerosis (MS) are commonly accompanied by optic neuritis (ON) that causes retinal ganglion cell (RGC) death and even vision loss. Nicotinamide adenine dinucleotide (NAD+) can protect against cell apoptosis and attenuate MS-triggered symptoms. However, the effect of NAD+ on MS-triggered ON remains unclear. Herein, experimental autoimmune encephalomyelitis (EAE) was established by immunizing female C57BL/6 mice with MOG35-55 peptide. To investigate the effect of NAD+ on ON prevention and treatment, EAE mice received 250 mg/kg NAD+ daily via intraperitoneal injection after immunization and EAE onset, respectively. EX-527 (10 mg/kg, SIRT1 inhibitor) was intraperitoneally injected every two days to explore the role of SIRT1 in NAD+-induced therapeutic effect on EAE. NAD+ intervention attenuated the severity of EAE in mice. NAD+ intervention relieved inflammatory infiltration and CD3+ and CD4+ cell infiltration and decreased the number and activation of microglia and astrocytes in the optic nerve. NAD+ intervention also attenuated demyelination, axonal loss, oligodendrocyte apoptosis and oligodendrocyte progenitor cell recruitment and proliferation in the optic nerve and protected against RGC apoptosis in the retina. NAD+ intervention decreased pro-inflammatory cytokine mRNA and pro-apoptotic protein expression and enhanced anti-inflammatory cytokine mRNA expression and the SIRT1 signaling in the optic nerve and retina and regulated the Th1/Th17/Tregs immune response in the spleen. In addition, EX-527 reversed the therapeutic effect of NAD+ on EAE, suggesting that NAD+ prevented MS-triggered ON by activating the SIRT1 signaling pathway. This study shows the potential of NAD+ to be used as a drug in preventing and treating MS-related ON.

17.
Neuroscience ; 468: 68-74, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119577

RESUMO

Mitochondrial permeability transition pore (mPTP) opening is critical to mitochondrial apoptosis during ischemic injury. Sirtuin 3 (Sirt3) is a mitochondrial deacetylase known to play a major role in stress resistance and cell death. Our previous studies have shown that Sirt3 activates superoxide dismutase 2 and forkhead box O3a to reduce cellular reactive oxygen species. However, it is unclear the interaction between Sirt3 and mPTP and the roles they play in ischemic stroke. We used the middle cerebral artery occlusion (MCAO) model, a mouse model of stroke, to examine Sirt3 and mPTP-related protein levels. We then applied lentivirus packaged Sirt3 overexpression in HT22 cells, a mouse hippocampal neuronal cell line, to investigate the underlying mechanism. We found Sirt3 protein level was decreased in the penumbra area in MCAO mice, along with an increase in mPTP related proteins, namely voltage-dependent anion channel 1 (VDAC1) and adenine nucleotide translocator 1 (ANT1). Sirt3 overexpression suppressed the increase in VDAC1, ANT1 and cleaved caspase 3 that were induced by the serum and glucose deprivation (SGD) condition. Our studies suggest that ischemic injury induced mPTP opening and apoptosis by reducing Sirt3. It helps to identify new therapeutic targets for ischemic stroke.

18.
Lancet ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34111416

RESUMO

BACKGROUND: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. FINDINGS: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. INTERPRETATION: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. FUNDING: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

19.
Hum Exp Toxicol ; : 9603271211021476, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34075790

RESUMO

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 (SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 (SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3ß signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

20.
J Cell Mol Med ; 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34133068

RESUMO

Ageing-related osteoporosis is becoming an emerging threat to human health along with the ageing of human population. The decreased rate of osteogenic differentiation and bone formation is the major cause of ageing-related osteoporosis. Microtubule actin cross-linking factor 1 (MACF1) is an important cytoskeletal factor that promotes osteogenic differentiation and bone formation. However, the relationship between MACF1 expression and ageing-related osteoporosis remains unclear. This study has investigated the expression pattern of MACF1 in bone tissues of ageing-related osteoporosis patients and ageing mice. The study has further elucidated the mechanism of MACF1 promoting bone formation by inhibiting HES1 expression and activity. Moreover, the therapeutic effect of MACF1 on ageing-related osteoporosis and post-menopausal osteoporosis was evaluated through in situ injection of the MACF1 overexpression plasmid. The study supplemented the molecular mechanisms between ageing and bone formation, and provided novel targets and potential therapeutic strategy for ageing-related osteoporosis.

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