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1.
J Cell Mol Med ; 2021 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-33938129

RESUMEN

Autophagy is closely associated with cerebral ischaemia/reperfusion injury, but the underlying mechanisms are unknown. We investigated whether Spautin-1 ameliorates cerebral ischaemia/reperfusion injury by inhibiting autophagy and whether its derived pyroptosis is involved in this process. We explored the mechanism of Spautin-1 in cerebral ischaemia/reperfusion. To answer these questions, healthy male Sprague-Dawley rats were exposed to middle cerebral artery occlusion for 60 minutes followed by reperfusion for 24 hours. We found that cerebral ischaemia/reperfusion increased the expression levels of autophagy and pyroptosis-related proteins. Treatment with Spautin-1 reduced the infarct size and water content and restored some neurological functions. In vitro experiments were performed using oxygen-glucose deprivation/reoxygenation to model PC12 cells. The results showed that PC12 cells showed a significant decrease in cell viability and a significant increase in ROS and autophagy levels. Spautin-1 treatment reduced autophagy and ROS accumulation and attenuated NLRP3 inflammasome-dependent pyroptosis. However, these beneficial effects were greatly blocked by USP13 overexpression, which significantly counteracted the inhibition of autophagy and NLRP3 inflammasome-dependent ferroptosis by Spautin-1. Together, these results suggest that Spautin-1 may ameliorate cerebral ischaemia-reperfusion injury via the autophagy/pyroptosis pathway. Thus, inhibition of autophagy may be considered as a promising therapeutic approach for cerebral ischaemia-reperfusion injury.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33977435

RESUMEN

A hybrid AQI time series prediction model is proposed based on EWT-SE-VMD secondary decomposition, ICA (imperialist competitive algorithm) feature selection, and ESN (echo state network) neural network. Firstly, EWT (empirical wavelet transform) and VMD (variational mode decomposition) are used to decompose the original AQI time series into several stable and reliable subseries. Then, the ICA is used to select features of the above subseries for the ESN prediction model. Finally, the optimized feature variables are put into the ESN deep network to establish a prediction model of each AQI subseries and obtain the future AQI index. According to the experimental results of the daily AQI series in Beijing, Tianjin, and Shijiazhuang, we find that (a) among all decomposition methods, the proposed secondary decomposition method (EWT-SE-VMD) performs best in processing data; (b) it is proved that the proposed hybrid model has broad application prospect and research value in the AQI prediction field.

3.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1795-1802, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33982484

RESUMEN

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.


Asunto(s)
Hiperlipidemias , Animales , Transporte Biológico , Colesterol/metabolismo , Dieta Alta en Grasa/efectos adversos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Hígado/metabolismo , Ratas , Ratas Sprague-Dawley , Triglicéridos/metabolismo
4.
Pain Physician ; 24(3): E367-E375, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33988959

RESUMEN

BACKGROUND: Numerous therapies have been developed for the treatment of chronic pelvic pain (CPP). Oxygen-ozone therapy is a new method for the treatment of CPP. OBJECTIVES: This article evaluated the feasibility of ultrasound-guided peritoneal perfusion with ozone in patients with CPP. STUDY DESIGN: This is a bicenter retrospective study. SETTING: The study was conducted at 2 pain centers of a university hospital. METHODS: The medical records of patients with CPP (n = 60) from March 2016 until October 2018 were collected and reviewed. Group A contained 19 patients who were treated with a 1500 mcg dose of ozonated water (10 mcg/mL concentration and 150 mL volume), group B contained 23 patients using the same dose of ozonated water but a 15 mcg/mL concentration and 100 mL volume. Group C included 18 patients using a similar ozone dose but delivered in an oxygen-ozone mixture (15 mcg/mL concentration and 100 mL volume oxygen-ozone mixture). Visual Analog Scale (VAS) scores for pain of the 3 groups were compared at pretreatment, posttreatment, 1, 3, and 6 months posttreatment. The injection pain was evaluated using a 4-point verbal rating scale. Quality of life (QoL), anxiety, and depression were assessed at pretreatment and at 6 months posttreatment. RESULTS: The VAS scores of the 3 groups decreased over time following treatment. Group A showed much higher pain scores compared with groups B and C at 1, 3, and 6 months posttreatment. However, the injection pain for groups B and C was higher than group A, but there was no difference seen between group B and C. At 6 months posttreatment, the QoL for all patients improved compared with pretreatment, whereas the anxiety and depression did not demonstrate differences. LIMITATIONS: The main limitations of this study are the retrospective study design, limited case number, and short follow-up period. CONCLUSIONS: Ultrasound-guided peritoneal perfusion with ozone is a feasible therapy for patients with CPP.

5.
Cell Death Dis ; 12(5): 489, 2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-33990548

RESUMEN

Tumor recurrence is the major obstacle for pushing the envelope of liver transplantation for hepatocellular carcinoma (HCC) patients. The inflammatory cascades activated by acute liver graft injury promote tumor recurrence. We aimed to explore the role and mechanism of myeloid-derived suppressor cell (MDSC) mobilization induced by liver graft injury on tumor recurrence. By analyzing 331 HCC patients who received liver transplantation, the patients with graft weight ratio (GWR, the weight of liver graft divided by the estimated standard liver weight of recipient) <60% had higher tumor recurrence than GWR ≥60% ones. MDSCs and CXCL10/TLR4 levels were significantly increased in patients with GWR <60% or tumor recurrence. These findings were further validated in our rat orthotopic liver transplantation model. In CXCL10-/- and TLR4-/- mice of hepatic ischemia/reperfusion injury plus major hepatectomy (IRH) model, monocytic MDSCs, instead of granulocytic MDSCs, were significantly decreased. Importantly, CXCL10 deficiency reduced the accumulation of TLR4+ monocytic MDSCs, and CXCL10 increased MDSC mobilization in the presence of TLR4. Moreover, MMP14 was identified as the key molecule bridging CXCL10/TLR4 signaling and MDSC mobilization. Knockout or inhibition of CXCL10/TLR4 signaling significantly reduced the tumor growth with decreased monocytic MDSCs and MMP14 in the mouse tumor recurrent model. Our data indicated that monocytic MDSCs were mobilized and recruited to liver graft during acute phase injury, and to promote HCC recurrence after transplantation. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent the therapeutic potential in decreasing post-transplant liver tumor recurrence.

6.
Mikrochim Acta ; 188(6): 181, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33954865

RESUMEN

Simultaneous cathodic and anodic electrochemiluminescence (ECL) emissions of needle-like nanostructures of Ru(bpy)32+ (RuNDs) as the only luminophore are reported based on different co-reactants. Cathodic ECL was attained from RuNDs/K2S2O8 system, while anodic ECL was achieved from RuNDs/black phosphorus quantum dots (BPQDs) system. Ferrocene attached to the hairpin DNA could quench the cathodic and anodic ECL simultaneously. Subsequently, the ECL signals recovered in the presence of tumor marker mucin 1 (MUC1), which made it possible to quantitatively detect MUC1. The variation of ECL signal was related linearly to the concentrations of MUC1 in the range 20 pg mL-1 to 10 ng mL-1, and the detection limits were calculated to 2.5 pg mL-1 (anodic system, 3σ) and 6.2 pg mL-1 (cathodic system, 3σ), respectively. The recoveries were 97.0%, 105%, and 95.2% obtained from three human serum samples, and the relative standard deviation (RSD) is 5.3%. As a proof of concept, this work realized simultaneous ECL emission of  a single luminophore, which initiates a new thought in biomarker ECL detection beyond the traditional ones. Simultaneous cathodic and anodic ECL emissions of RuNDs were reported based on different co-reactants. Ferrocene could quench the ECL emission in the cathode and the anode simultaneously. Thus, an aptasensor was constructed based on the variation of ECL intensity. As a proof of concept, this work realized simultaneous ECL emission of a single luminophore, which initiates a new thought in biomarker ECL detection beyond the traditional ones by avoiding the false positive signals.

7.
J Colloid Interface Sci ; 599: 88-99, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33933800

RESUMEN

Amphiphilic Janus particles are characterized by their anisotropic morphology and unique physical and chemical properties. In the present research, amphiphilic Janus particles were used as stabilizing agents to prepare a fluorine-containing polyacrylate composite emulsion. The influences of the structure and dosage of amphiphilic Janus SiO2 particles and the amount of fluorine-containing monomer hexafluorobutyl methacrylate on the stability of the composite emulsion were investigated. It was noticed that when the hydrophilic and hydrophobic groups of Janus SiO2 particles were polyacrylamide and polymethyl methacrylate, respectively, the stabilization of the polyacrylate emulsion with Janus SiO2 particles was achieved. When 0.3 wt% of polyacrylamide/polymethyl methacrylate amphiphilic Janus SiO2 particles and 8 wt% of hexafluorobutyl methacrylate were used, a stable composite emulsion was obtained. The conversion rate reached 98.7% with an average particle size of 500 nm. The composite emulsion was applied for fabric finishing. The water contact angle of the fabric increased from 21.4° to 140.2°, demonstrating its greatly improved hydrophobicity. Therefore, it could be inferred that the synergistic effect of amphiphilic Janus SiO2 nanoparticles and hexafluorobutyl methacrylate improved the water resistance of the latex film.

8.
Biomed Res Int ; 2021: 5549796, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33977104

RESUMEN

Objective: The role of trimethylamine N-oxide (TMAO) in cardiovascular diseases has been highlighted. Nevertheless, the associations of large-artery atherosclerotic (LAA) stroke with TMAO and blood lipid-related indices are little investigated. Methods: A cross-sectional comparative study was performed on 50 patients with LAA stroke and 50 healthy controls. Basic demographic data, common vascular risk factors, and blood lipid-related indices were collected. Plasma TMAO was detected through liquid chromatography tandem mass spectrometry. Multivariable unconditional logistic regression analyses were run to assess the associations of LAA stroke with plasma TMAO level and blood lipid-related indices. The area under the curve (AUC) of the receiver operating characteristic (ROC) was computed to assess the diagnostic performance of plasma TMAO level and blood lipid-related indices for LAA stroke. Results: Compared with healthy controls, the elevated plasma TMAO level (odds ratio [OR], 7.03; 95% confidence interval [CI], 2.86, 17.25; p < 0.01) and Apo-B (OR, 1.74; 95% CI, 1.06, 2.85; p = 0.03) were observed in LAA stroke patients, while lower Apo-A1 (OR, 0.56; 95% CI, 0.34, 0.91; p = 0.02), Apo-A1 to Apo-B ratio (OR, 0.29; 95% CI, 0.15, 0.56; p < 0.01), and HDL-C (OR, 0.56; 95% CI, 0.35, 0.91; p = 0.02) were found in LAA stroke patients after adjusted for age and gender. Moreover, plasma TMAO (AUC, 0.89; 95% CI, 0.83, 0.95), Apo-A1 (AUC, 0.81; 95% CI, 0.72, 0.89), Apo-B (AUC, 0.81; 95% CI, 0.73, 0.90), Apo-A1 to Apo-B ratio (AUC, 0.85; 95% CI, 0.78, 0.93), and HDL-C (AUC, 0.81; 95% CI, 0.72, 0.89) showed good diagnostic values for LAA stroke in adjusted models. Conclusions: The plasma TMAO level, Apo-A1, Apo-B, and HDL-C are important biomarkers for LAA stroke patients.

9.
Dis Markers ; 2021: 5597401, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33981369

RESUMEN

Test anxiety creates barriers to learning and performance, which further affects students' social, behavioural, and emotional development. Currently, the medication to treat test anxiety has not been reported yet. Here, we enrolled 120 students to evaluate the effect of probiotic supplement preparation (PSP) on test anxiety from the aspect of the intestinal microbiota. We found that the intake of PSP alleviated the symptoms of depression and anxiety in students with test anxiety by evaluating their mental state using the Hamilton Depression Rating Scale and Hamilton Anxiety Scale. High-throughput sequencing results indicated that the consumption of PSP increased the abundance of Streptococcus and Akkermansia that was lowered by the anxiety state in the intestinal microbiota of students. Meanwhile, taking PSP reduced the level of intestinal pathogens of Fusobacterium and Clostridium as well. In conclusion, our work shows that PSP can reduce test anxiety and restore the disturbed microbiota to the standard level in Chinese college students, rendering the use of PSP a promising strategy for test anxiety.

10.
Biomaterials ; 274: 120850, 2021 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-33984637

RESUMEN

Extracellular vesicles (EVs) are extracellular nanovesicles that deliver diverse cargoes to the cell and participate in cell communication. Mesenchymal stem cell (MSCs)-derived EVs are considered a therapeutic approach in musculoskeletal degenerative diseases, including intervertebral disc degeneration. However, limited production yield and unstable quality have impeded the clinical application of EVs. In the present study, it is indicated that metformin promotes EVs release and alters the protein profile of EVs. Metformin enhances EVs production via an autophagy-related pathway, concomitantly with the phosphorylation of synaptosome-associated protein 29. More than quantity, quality of MSCs-derived EVs is influenced by metformin treatment. Proteomics analysis reveals that metformin increases the protein content of EVs involved in cell growth. It is shown that EVs derived from metformin-treated MSCs ameliorate intervertebral disc cells senescence in vitro and in vivo. Collectively, these findings demonstrate the great promise of metformin in EVs-based intervertebral disc regeneration.

11.
J Asian Nat Prod Res ; : 1-17, 2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-33985386

RESUMEN

A series of novel pleuromutilin derivatives were designed and synthesized based on the twin drugs theory. Piperazinyl and thioether were used as the linkage to connect the pleuromutilin nuclear and sulfonamide to improve the biological activity and water solubility of derivatives. The in vitro antibacterial activities against drug-sensitive and drug-resistance bacteria were evaluated by agar dilution method. Most of the 25 compounds displayed excellent antibacterial activities against drug-sensitive bacteria, particularly, five compounds (9, 10, 11, 14a and 14b) exerted the excellent antibacterial activities against drug-resistance bacteria.

12.
Wei Sheng Yan Jiu ; 50(2): 289-300, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33985639

RESUMEN

OBJECTIVE: To explore the toxic effect of bisphenol A on the liver, as well as the influence effect on lipid metabolism. METHODS: The toxic effects of bisphenols on human health were studied by using in vivo experiments of bisphenol A exposure in rats and in vitro experiments of human liver cell line HL-7702. Male SD rats were divided into control group(Ctrl), 1 mg/(kg·d) group(low), 5 mg/(kg·d) group(medium) and 25 mg/(kg·d) group(high) for 14 days subacute exposure of bisphenol A, to evaluate the toxic effect of bisphenol A on the liver in terms of body weight, liver organ index, liver pathological tissue sections, serum biochemical indicators. Then HL-7702 was divided into four groups: control group(Ctrl), low concentration treatment group(0. 16 µmol/L), medium concentration treatment group(4 µmol/L) and high concentration treatment group(100 µmol/L). After 24 hours of exposure to bisphenol A, the contents of triglyceride(TG) and total cholesterol(TC) in cells, reactive oxygen species(ROS) levels were detected, and the transcription levels of genes related to lipid metabolism and oxidative stress were detected by fluorescent quantitative PCR. RESULTS: The 14-day subacute exposure had no significant effect on rat body weight and liver body weight ratio, but liver pathological sections clearly showed that bisphenol A exposure can damage liver tissue structure. Serum biochemical indicator of total bile acid(TBA) was significantly reduced in the high-dose group, which was(4. 75±0. 33)µmol/L, creatinine(Cr) was significantly increased in the medium and high-dose group, which were(18. 00±0. 76)µmol/L and(18. 83±0. 75)µmol/L, respectively. TC, high-density lipoprotein(HDL-C) and low-density lipoprotein(LDL-C) were significantly reduced in the middle-and high-dose groups(P<0. 05), which were(1. 44±0. 10), (1. 14±0. 10)mmol/L;(0. 84±0. 04), (0. 63±0. 07)mmol/L and(0. 21±0. 04), (0. 16±0. 05)mmol/L, respectively. Bisphenol A exposure could significantly reduce the content of TC in hepatocytes(P<0. 05). BPA treatment could significantly increase ROS levels in HL-7702 cells. The transcription level of PPARα was significantly increased in the high concentration group, FABP1 was significantly increased in the high concentration group, SOD1 was significantly decreased in the medium and high concentration group(P<0. 05). CONCLUSION: Bisphenol A may cause oxidative stress by inducing excessive ROS production in liver cells, leading to liver damage and disorder of lipid metabolism in the body, thereby showing liver toxicity.

13.
Oncogene ; 2021 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-33986510

RESUMEN

The mortality rate of esophageal squamous cell carcinoma (ESCC) is higher than that of other cancers worldwide owing to a lack of therapeutic targets and related drugs. This study aimed to find new drugs by targeting an efficacious therapeutic target in ESCC patients. Signal transducer and activator of transcription 3 (STAT3) is hyperactive in ESCC. Herein, we identified a novel STAT3 inhibitor, periplogenin, which strongly inhibited phosphorylation of STAT3 at Tyr705. Docking models and pull-down assays revealed that periplogenin bound directly and specifically to STAT3, leading to significant suppression of subsequent dimerization, nuclear import, and transcription activities. In addition, STAT3 knockdown cell lines were insensitive to periplogenin, whereas in contrast, STAT3-overexpressing cells were more sensitive to periplogenin, indicating that STAT3 was a target of periplogenin. Intraperitoneally administered periplogenin exhibited efficacious therapeutic effects in ESCC patient-derived xenograft models and dramatically impaired the phosphorylation of STAT3 and expression levels of STAT3-mediated downstream genes. Thus, our study demonstrated that periplogenin acted as a new STAT3 inhibitor, suppressing the growth of ESCC in vitro and in vivo, providing a basis for its potential application in ESCC treatment and prevention.

15.
Sci Total Environ ; 786: 147278, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33964779

RESUMEN

Developing cleaner and affordable alternatives to the sole reliance on fossil fuels has intensified efforts to improve the thermochemical conversion property of the second-generation lignocellulosic biomass. This study aimed to explore the effects of the two torrefaction temperatures (200 and 300 °C), the two reaction atmospheres (N2/O2 and CO2/O2), and the three heating rates (5, 10, and 15 °C/min) on the combustion regime of water hyacinth (WH). Decomposition behaviors, reaction kinetics, thermodynamics, and mechanisms, evolved emissions and functional groups, and fuel microstructure properties were quantified. The deoxygenation and dehydration reactions acted as the main drivers of the torrefaction process, with the peak degree of deoxygenation of 86.21% for WH torrefied at 300 °C (WH300). WH300 significantly reduced the quantity of oxygen-containing functional groups and altered the fuel microstructure properties. The order of the decomposition rates of the pseudo-components were hemicellulose > cellulose > lignin for both WH and WH torrefied at 200 °C (WH200) and cellulose > lignin > hemicellulose for WH300. The average activation energy fell from 197.71 to 195.71 kJ/mol for WH, 287.90 to 195.97 kJ/mol for WH200, and 226.92 to 184.94 kJ/mol for WH300 when the atmosphere changed from N2/O2 to CO2/O2. The heating rate exerted a stronger control on their combustion behaviors than did the reaction atmosphere. CO2, NO, and NO2 emissions dropped by 46.0, 53.1, and 65.9% for WH200 and 29.6, 42.8, and 62.5% for WH300, respectively, when compared to WH. 473.7 °C, 5 °C/min, and the CO2/O2 atmosphere were the optimal settings for the maximized combustion efficiency. 717.1 °C was determined as the optimal setting for the minimized combustion emissions. Our study can yield new insights into the large-scale and cleaner combustion of the torrefied water hyacinth.

16.
N Engl J Med ; 384(19): 1789-1799, 2021 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-33979487

RESUMEN

BACKGROUND: Official recommendations differ regarding tympanostomy-tube placement for children with recurrent acute otitis media. METHODS: We randomly assigned children 6 to 35 months of age who had had at least three episodes of acute otitis media within 6 months, or at least four episodes within 12 months with at least one episode within the preceding 6 months, to either undergo tympanostomy-tube placement or receive medical management involving episodic antimicrobial treatment. The primary outcome was the mean number of episodes of acute otitis media per child-year (rate) during a 2-year period. RESULTS: In our main, intention-to-treat analysis, the rate (±SE) of episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P = 0.66). Because 10% of the children in the tympanostomy-tube group did not undergo tympanostomy-tube placement and 16% of the children in the medical-management group underwent tympanostomy-tube placement at parental request, we conducted a per-protocol analysis, which gave corresponding episode rates of 1.47±0.08 and 1.72±0.11, respectively. Among secondary outcomes in the main analysis, results were mixed. Favoring tympanostomy-tube placement were the time to a first episode of acute otitis media, various episode-related clinical findings, and the percentage of children meeting specified criteria for treatment failure. Favoring medical management was children's cumulative number of days with otorrhea. Outcomes that did not show substantial differences included the frequency distribution of episodes of acute otitis media, the percentage of episodes considered to be severe, and antimicrobial resistance among respiratory isolates. Trial-related adverse events were limited to those included among the secondary outcomes of the trial. CONCLUSIONS: Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02567825.).

17.
Sci Rep ; 11(1): 9495, 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33947913

RESUMEN

Insulin aspart (IAsp) is one of the main therapies used to control blood glucose after a meal. This study aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 rapid-acting IAsp products: a new IAsp biosimilar (RD10046) and NovoRapid. In a single-center, randomized, single-dose, 2-period, crossover, euglycemic clamp study (registry number: CTR20180517, registration date: 2018-05-30), healthy Chinese males were randomized to receive 0.2 U/kg of the IAsp biosimilar RD10046 and NovoRapid under fasted conditions on two separate occasions. PK and PD were assessed for up to 10 h. Of the 30 randomized subjects, all 30 completed both treatment periods. The PK (area under the curve [AUC] of total IAsp; maximum observed IAsp concentration [Cmax]) and PD (maximum glucose infusion rate [GIRmax]; total glucose infusion during the clamp [AUCGIR,0-10h]) were similar between the new IAsp biosimilar RD10046 and NovoRapid. In all cases, the 90% CIs for the ratios of the geometric means were completely contained in the prespecified acceptance limits of 0.80-1.25. No hypoglycemic events, allergic reactions, or local injection adverse reactions occurred in this trial. We concluded that the studied IAsp biosimilar (RD10046) was bioequivalent to NovoRapid.

18.
Lung Cancer ; 156: 82-90, 2021 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-33933895

RESUMEN

OBJECTIVES: To explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT-CHT) with intensity modulated radiotherapy (IMRT) technique in non-small cell lung cancer (NSCLC) patients with postoperative locoregional recurrence (LRR). MATERIALS AND METHODS: NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT-CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a break. Patients with no disease progression and no persistent Grade ≥2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS). RESULTS: Fifty-eight patients were enrolled and analyzed. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7 % and 46.4 %, the 2-year and 3-year OS rate was 72.5 % and 52.2 %, respectively, and a favorable objective response rate of 95.9 % was obtained after the whole courses protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4 %) and 7 (12.1 %) patients, and fatal pneumonitis was reported in one case (1.7 %). Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1 % vs. 46.9 %,P = 0.001; 2-year OS, 100 % vs. 59.4 %, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8 % vs. 47.4 %, P = 0.008; 2-year OS, 100 % vs. 63.0 %, P = 0.001), and gross tumor volume (GTV) (<50cm3 vs. ≥ 50cm3: 2-year PFS, 70.6 % vs. 46.2 %, P = 0.024; 2-year OS, 85.6 % vs. 57.4 %, P = 0.034) were significantly associated with PFS and OS. CONCLUSION: Split-course HFRT-CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR of NSCLC. Good PS, a single recurrence site and GTV<50cm3 tended to have prolonged PFS and OS. Early detection of LRR may improve the efficacy of HFRT-CHT.

19.
Bioengineered ; 12(1): 1611-1626, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33944676

RESUMEN

Multiple myeloma (MM), a malignancy of plasma cells mainly derived from the bone marrow, has remained incurable generally. LncRNA MALAT1 has been reported to be upregulated in the MM cells and knockdown of MALAT1 inhibited MM cell cycle progression and enhanced cell apoptosis. Online target prediction showed that two target sites for MALAT1 existed in miR-188-5p, which has been identified as a tumor suppressor in other types of cancers. However, the role of miR-188-5p in the MM and whether miR-188-5p mediates the MM tumor progression regulated by MALAT1 are still unknown. Herein, four main MM cell lines were adopted to investigate the effects of miR-188-5p on cell proliferation and apoptosis via transfection with miR-188-5p mimic/inhibitor and co-transfection with miR-188-5p inhibitor and MALAT1-shRNA plasmids. Xenograft tumor model was also established to study these effects in vivo. Overexpression of miR-188-5p inhibited cell viability, cell proliferation as well as tumor growth and arrested cell cycle at G1 to S transition, but miR-188-5p knockdown showed opposite effects on the MM cells in vitro and in vivo. Moreover, MALAT1 was shown to be inversely correlated with miR-188-5p expression through direct binding to miR-188-5p, and in turn, miR-188-5p could mediate the MM cell proliferation and apoptosis regulated by MALAT1. These findings indicate that miR-188-5p serves as a tumor suppressor in the progression of the MM and is directly involved in MM cell proliferation and apoptosis regulated by MALAT1, which may provide a potential therapeutic target or prognostic indictor for MM clinical treatment.

20.
Hum Vaccin Immunother ; : 1-7, 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33945439

RESUMEN

Background: To evaluate the persistence of antibody for 10 years, and investigate the effect of one or two booster doses with Kanghua human diploid cells rabies vaccine (HDCV) in China.Methods: Participants were re-recruited at year 10 post the primary phase 3 clinical study. Some of them in Kanghua HDCV group who had been boosted one dose at year 8, received one more dose at this boosted study. Participants who never boosted were randomly assigned to boost 1 or 2 doses of Kanghua HDCV. Blood samples were collected at day 0, 1, 3, 7, and 14. Safety was evaluated from day 0-14.Results: At year 10 after primary vaccination, the seroconversion rates of neutralizing antibody were 98.28-100% in Kanghua and Pasteur groups.After booster, the seroconversion rate in each group reached to 100% from day 7 to day 14. GMCs were similar in the groups with the same booster doses, and two doses of booster induced higher levels of antibody. The reported rates of solicited local and systemic adverse reaction were low, and no serious adverse events were found through the boosted study.Conclusion: 5 doses of Kanghua HDCV maintained long-term immunity at least 10 years. One or two doses of booster, rapidly triggered 100% protection against rabies virus.Trial registration: ClinicalTrials.gov: NCT03774628.

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