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1.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638747

RESUMO

Amphiphilic copolymers with pendant functional groups in polyester segments are widely used in nanomedicine. These enriched functionalities are designed to form covalent conjugates with payloads or provide additional stabilization effects for encapsulated drugs. A general method is successfully developed for the efficient preparation of functional biodegradable PEG-polyester copolymers via click chemistry. Firstly, in the presence of mPEG as initiator, Sn(Oct)2-catalyzed ring-opening polymerization of the α-alkynyl functionalized lactone with D,L-lactide or ε-caprolactone afforded linear mPEG-polyesters bearing multiple pendant alkynyl groups. Kinetic studies indicated the formation of random copolymers. Through copper-catalyzed azide-alkyne cycloaddition reaction, various small azido molecules with different functionalities to polyester segments are efficiently grafted. The molecular weights, polydispersities and grafting efficiencies of azido molecules of these copolymers were investigated by NMR and GPC. Secondly, it is demonstrated that the resulting amphiphilic functional copolymers with low CMC values could self-assemble to form nanoparticles in aqueous media. In addition, the in vitro degradation study and cytotoxicity assays indicated the excellent biodegradability and low cytotoxicity of these copolymers. This work provides a general approach toward the preparation of functional PEG-polyester copolymers in a quite efficient way, which may further facilitate the application of functional PEG-polyesters as drug delivery materials.

2.
J Orthop Surg Res ; 16(1): 588, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641943

RESUMO

BACKGROUND: Ultrasound examination can be applied to the diagnosis of pediatric elbow fracture. This study aims to analyze the application value of ultrasound in the surgical treatment of supracondylar humeral fractures. METHODS: 64 children with supracondylar humeral fractures were treated with ultrasound-guided closed reduction and percutaneous pinning (CRPP), 31 patients were treated with CRPP under radiography guidence. The reduction effect of supracondylar humeral fractures was determined through the perioperative ultrasound images of the lateral, medial and posterior aspects of the elbow. Percutaneous pinning was performed after supracondylar humeral fractures were well reduced. A follow-up examination was performed and all the patients were evaluated according to Flynn's criteria. RESULTS: The mean duration of surgery was 58.3 min (42-108 min) in the ultrasound group and 41.5 min (24-63 min) in the radiography group (P < 0.05). The mean carrying angle was 8.2° (0°-15°) in the ultrasound group and 9.4°(3°-16°) in the radiography group; The mean Baumann's angle was 75.5°(60°-85°) in the ultrasound group and 73.4°(62°-82°) in the radiography group; The mean lateral humerocapitellar angle was 38.4° (26°-54°) in the ultrasound group and 41.6°(29°-52°) in the radiography group; No significant differences were observed between the two groups. According to the Flynn's criteria, 49 (76.6%) patients had excellent, 10 (15.6%) patients achieved good, 3 (4.7%) patients showed fair results and 2 (3.1%) patients achieved poor results in the ultrasound group; 22 (70.9%) patients had excellent, 6 (19.4%) patients achieved good, 2 (6.5%) patients showed fair results and 1 (3.2%) patients achieved poor results in the radiography group; No statistically significant difference was noted between the results of these two groups (P > 0.05). After surgery, three patients had pin tract infection. One patient had ulnar nerve neurapraxia in the radiography group. No cases with Volkmann's contracture were reported. CONCLUSION: Ultrasound-guided CRPP is a safe and reliable surgical treatment of pediatric supracondylar humeral fractures. Trial registration Retrospectively registered.

3.
Cell Prolif ; : e13135, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34632655

RESUMO

OBJECTIVES: Autophagy, a highly conserved lysosomal degradation process in eukaryotic cells, has been widely reported closely related to the progression of many types of human cancers, including LGG; however, the intricate relationship between autophagy and LGG remains to be clarified. MATERIALS AND METHODS: Multi-omics methods were used to integrate omics data to determine potential autophagy regulators in LGG. The expression of ZFP36L2 and RAB13 in SW1088 cells was experimentally manipulated using cDNAs and small interfering RNAs (siRNA). RT-qPCR detects RNAi gene knockout and cDNA overexpression efficiency. The expression levels of proteins in SW1088 cells were evaluated using Western blot analysis and immunofluorescence analysis. Homology modelling and molecular docking were used to identify compounds from Multi-Traditional Chinese Medicine (TCM) Databases. The apoptosis ratios were determined by flow cytometry analysis of Annexin-V/PI double staining. We detect the number of autophagosomes by GFP-MRFP-LC3 plasmid transfection to verify the process of autophagy flow. RESULTS: We integrated various omics data from LGG, including EXP, MET and CNA data, with the SNF method and the LASSO algorithm, and identified ZFP36L2 and RAB13 as positive regulators of autophagy, which are closely related to the core autophagy regulators. Both transcription level and protein expression level of the four autophagy regulators, including ULK1, FIP200, ATG16L1 and ATG2B, and LC3 puncta were increased by ZFP36L2 and RAB13 overexpression. In addition, RAB13 participates in autophagy through ATG2B, FIP200, ULK1, ATG16L1 and Beclin-1. Finally, we screened multi-TCM databases and identified gallic acid as a novel potential RAB13 inhibitor, which was confirmed to negatively regulate autophagy as well as to induce cell death in SW1088 cells. CONCLUSION: Our study identified the key autophagic regulators ZFP36L2 and Rab13 in LGG progression, and demonstrated that gallic acid is a small molecular inhibitor of RAB13, which negatively regulates autophagy and provides a possible small molecular medicine for the subsequent treatment of LGG.

4.
Oxid Med Cell Longev ; 2021: 1552127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630845

RESUMO

NLRP3 inflammasome-mediated pyroptosis is a proinflammatory programmed cell death pathway, which plays a vital role in functional outcomes after stroke. We previously described the beneficial effects of curcumin against stroke-induced neuronal damage through modulating microglial polarization. However, the impact of curcumin on microglial pyroptosis remains unknown. Here, stroke was modeled in mice by middle cerebral artery occlusion (MCAO) for 60 minutes and treated with curcumin (150 mg/kg) intraperitoneally immediately after reperfusion, followed by daily administrations for 7 days. Curcumin ameliorated white matter (WM) lesions and brain tissue loss 21 days poststroke and improved sensorimotor function 3, 10, and 21 days after stroke. Furthermore, curcumin significantly reduced the number of gasdermin D+ (GSDMD+) Iba1+ and caspase-1+Iba1+ microglia/macrophage 21 days after stroke. In vitro, lipopolysaccharide (LPS) with ATP treatment was used to induce pyroptosis in primary microglia. Western blot revealed a decrease in pyroptosis-related proteins, e.g., GSDMD-N, cleaved caspase-1, NLRP3, IL-1ß, and IL-18, following in vitro or in vivo curcumin treatment. Mechanistically, both in vivo and in vitro studies confirmed that curcumin inhibited the activation of the NF-κB pathway. NLRP3 knocked down by siRNA transfection markedly increased the inhibitory effects of curcumin on microglial pyroptosis and proinflammatory responses, both in vitro and in vivo. Furthermore, stereotaxic microinjection of AAV-based NLRP3 shRNA significantly improved sensorimotor function and reduced WM lesion following curcumin treatment in MCAO mice. Our study suggested that curcumin reduced stroke-induced WM damage, improved functional outcomes, and attenuated microglial pyroptosis, at least partially, through suppression of the NF-κB/NLRP3 signaling pathway, further supporting curcumin as a potential therapeutic drug for stroke.

5.
Small ; : e2104747, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647419

RESUMO

Electrospun nanofiber membranes have been widely used for guided bone regeneration (GBR). For assistance in bone healing, photothermal therapy which renders moderate heat stimulation to defect regions by near-infrared (NIR) light irradiation has attracted much attention in recent years. Combined with photothermal therapy, novel electrospun poly(ε-caprolactone)/molybdenum disulfide (PCL/MoS2 ) nanofiber membranes are innovatively synthesized as GBR for bone therapy, wherein the exfoliated MoS2 nanosheets served as osteogenic enhancers and NIR photothermal agents. With the doping of MoS2 , the mechanical properties of nanofiber membranes got improved with the degradation unaffected. The composite PCL/MoS2 membranes show enhanced cell growth and osteogenic performance compared with PCL alone. Under NIR-triggered mild photothermal therapy, osteogenesis and bone healing are accelerated by using PCL/MoS2 nanofiber membranes for growth of bone mesenchymal stem cells in vitro and repair of rat tibia bone defect in vivo. The novel nanofiber membranes may be developed as intelligent GBR in the therapy of bone defects.

6.
Br J Pharmacol ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625952

RESUMO

BACKGROUND AND PURPOSE: In chronic kidney disease (CKD), patients inevitably reach end-stage renal disease and require renal replacement therapies. Emerging evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of the metabolite 1-hydroxypyrene in mediating renal fibrosis. EXPERIMENTAL APPROACH: We analysed 5406 urine and serum samples from patients with stage 1-5 CKD using metabolomics, and 1-hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine-induced rats. KEY RESULTS: We identified correlations between the urine and serum levels of 1-hydroxypyrene and the estimated glomerular filtration rate in patients with CKD onset and progression. Moreover, increased 1-hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Upregulated mRNA expression of aryl hydrocarbon receptors (AhR) and its target genes, including CYP1A1, CYP1A2, and CYP1B1, was observed in both patients and rats with progressive CKD. Our study further showed upregulated mRNA expression of AhR and its three target genes and upregulated nuclear AhR protein levels in mice and HK-2 cells treated with 1-hydroxypyrene, which caused accumulation of extracellular matrix components. Furthermore, treatment with AhR short hairpin RNA or flavonoids inhibited mRNA expression of AhR and its target genes in 1-hydroxypyrene-induced HK-2 cells and mice. CONCLUSION AND IMPLICATIONS: Metabolite 1-hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the AhR signalling pathway. Therefore, targeting AhR may be an alternative therapeutic strategy for CKD progression.

7.
Sci Prog ; 104(3_suppl): 368504211041497, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34533074

RESUMO

The generator is the most popular mobile power device and backup power device in the world. It is very important for human life. Therefore, it is important to develop more efficient combustion technology in order to save energy and reduce air pollution. In this paper, a novel technology of hydrogen and oxygen compound gasoline fuel is developed. Hydrogen and oxygen gases are produced from an electrolytic cell and then mixed with the intake gasoline and air. The compound fuel is sucked into the engine combustion chamber. The hydrogen and oxygen gases can be produced immediately without any storage device of hydrogen. The experimental results show that this technology can increase the power generation and decrease emission pollution due to promoting combustion efficiency. In addition, the spark plug seat temperature increases due to higher heat value of hydrogen. This technique can reduce carbon monoxide and HC, but increase carbon dioxide. The research and development of this technique can achieve the goals of energy saving, emission reduction, relative safety, easy refitting and low refitting expense. Moreover, this research possesses academic innovation and industrial application.

8.
Am J Gastroenterol ; 116(9): 1924-1928, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465694

RESUMO

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Feminino , Fluorenos/administração & dosagem , Hepatite C/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
9.
Curr Med Chem ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34514982

RESUMO

Protein-ligand interactions are necessary for majority protein functions. Adenosine-5'-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is cost-ineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

10.
ACS Nano ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515484

RESUMO

The active phase and catalytic mechanisms of Ni-based layered double hydroxide (LDH) materials for oxygen evolution reaction (OER) have no common consensus and remain controversial. Moreover, engineering the site activity and the number of active sites of LDHs is an efficient approach to advance the OER activity, as the thickness and stacking structure of the LDHs layer limit the catalytic activity. This work presents an interesting in situ approach of tuning the site activity and number of active sites of NiMn-LDHs, which exhibit the superior OER performance (onset overpotential of 0.17 V and overpotential of 0.24 V at 10 mA cm-2). The fundamental mechanistic insights and active phases during the OER process are characterized by in operando techniques along with the computational density functional theory calculations, revealing that the Ni site constitutes the OER activity and the dynamically generated NiOOH moiety is the active phase. We also prove that Ni sites undergo a reversible oxidation state under the working conditions to create active NiOOH species which catalyze the water to generate oxygen. These findings suggest that the Ni(III) phase in NiMn-LDHs is the OER active site and Mn promotes the electronic properties of Ni sites. Utilizing in situ/in operando techniques and theoretical calculation, we find that the in situ intercalation of guest anions allows the expansion of the LDH layers and keeps the active NiOOH species under the oxidation state of +3 via electron coupling, which ultimately tunes the site populations and site activity toward the superior OER activity, respectively. This work thus targets to provide insight into strategies to design the next generation of highly active catalysts for water electrolysis and fuel cell technologies.

11.
Eur J Pharmacol ; 910: 174468, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478692

RESUMO

Acute kidney injury (AKI) is one of the major complications with increased oxidative stress and inflammation in diabetic patients. Hyperglycemia stimulates the formation of advanced glycation end products (AGEs). However, hyperglycemia directly triggers the interaction between AGEs and transmembrane AGEs receptors (RAGE), which enhances oxidative stress and increases the production of inflammatory substances. Therefore, diabetes plays a pivotal role in kidney injury. Hydralazine, a vasodilator and antihypertensive drug, was found to have the ability to reduce ROS, oxidative stress, and inflammation. We applied Hydralazine co-culture with AGEs in rat mesangial cells (RMC) and to renal ischemia/reperfusion(I/R) injury models in streptozotocin-induced diabetic rats. Hydralazine significantly decreased AGEs-induced RAGE, iNOS, and COX-2 expressions in RMC. Compared to the diabetic with AKI group, hydralazine decreased inflammation-related protein, and JAK2, STAT3 signaling in rat kidney tissue. Our studies indicate that Hydralazine has the potential to become a beneficial drug in the treatment of diabetic acute kidney injury.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34468116

RESUMO

Aluminum and its alloys are widely used in various industries. Aluminum plays an important role in heat transfer applications, where enhancing the overall system performance through surface nanostructuring is achieved. Combining optimized nanostructures with a conformal hydrophobic coating leads to superhydrophobicity, which enables coalescence induced droplet jumping, enhanced condensation heat transfer, and delayed frosting. Hence, the development of a rapid, energy-efficient, and highly scalable fabrication method for rendering aluminum superhydrophobic is crucial. Here, we employ a simple, ultrascalable fabrication method to create boehmite nanostructures on aluminum. We systematically explore the influence of fabrication conditions such as water immersion time and immersion temperature, on the created nanostructure morphology and resultant nanostructure length scale. We achieved optimized structures and fabrication procedures for best droplet jumping performance as measured by total manufacturing energy utilization, fabrication time, and total cost. The wettability of the nanostructures was studied using the modified Cassie-Baxter model. To better differentiate performance of the fabricated superhydrophobic surfaces, we quantify the role of the nanostructure morphology to corresponding condensation and antifrosting performance through study of droplet jumping behavior and frost propagation dynamics. The effect of aluminum substrate composition (alloy) on wettability, condensation and antifrosting performance was investigated, providing important directions for proper substrate selection. Our findings indicate that the presence of trace alloying elements play a previously unobserved and important role on wettability, condensation, and frosting behavior via the inclusion of defect sites on the surface that are difficult to remove and act as pinning locations to increase liquid-solid adhesion. Our work provides optimization strategies for the fabrication of ultrascalable aluminum and aluminum alloy superhydrophobic surfaces for a variety of applications.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34368989

RESUMO

BACKGROUND AND AIM: Gastrointestinal stromal tumors (GISTs) are among the most common submucosal tumors in the stomach that require therapeutic intervention. We aim to identify the predictors of technical difficulty during endoscopic resection of gastric GIST and to investigate follow-up outcomes. METHODS: Patients with gastric GISTs were reviewed from June 2009 to June 2020 at Zhongshan Hospital. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed. A nomogram was developed and validated internally and externally. RESULTS: A total of 628 GISTs were finally analyzed. The difficulty was experienced in 66 cases. GISTs size (2-3 cm: OR 2.431 P = 0.018 and > 3 cm: OR 9.765 P < 0.001), invasion depth beyond submucosal (MP: OR 2.280, P = 0.038 and MP-ex: OR 4.295, P = 0.002), and lack of experience (OR 2.075, P = 0.016) were independent risk factors of difficulty. The nomogram prediction model showed a bias-corrected C-index value of 0.778 and acquired an area under curve (AUC) of 0.756 on the external validation cohort. At the cut-off of 0.15, the nomogram's negative predictive value (NPV) and accuracy (ACC) were 94.9% and 79.8% in identifying non-difficult GISTs. Follow-up results showed that only five GIST patients had local recurrence after endoscopic resection. CONCLUSIONS: Tumor size, invasion depth, and endoscopists' experience were risk factors for the difficulty of endoscopic GIST resection. Our nomogram provided a valuable tool for screening non-difficult GIST resection.

14.
Arthroscopy ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34358641

RESUMO

PURPOSE: To compare the kinematics of anterolateral structure (ALS) reconstruction (ALSR) and lateral extra-articular tenodesis (LET) in ACL-ALS-deficient knees with anterior cruciate ligament (ACL) reconstruction. METHODS: Ten fresh-frozen cadaveric knees with the following conditions were tested: (1) intact, (2) ACL-ALS deficiency, (3) ACL reconstruction (ACLR), (4) ACLR combined with ALSR (ACL-ALSR) or LET (ACLR+LET). Anterior translation and tibial internal rotation were measured with 90-N anterior load and 5 N·m internal torque at 0°, 30°, 60°, and 90°. The anterolateral translation and internal rotation were also measured during a simulated pivot-shift test at 0°, 15°, 30°, and 45°. The knee kinematic changes in all reconstructions were compared with each other, with intact knees as the baseline. RESULTS: Isolated ACLR failed to restore native knee kinematics in ACL-ALS-deficient knees. Both ACL-ALSR and ACLR+LET procedures decreased the anterior instability of the ACLR. However, ACLR+LET caused overconstraints in internal rotation at 30° (-3.73° ± 2.60°, P = .023), 60° (-4.96° ± 2.22°, P = .001) and 90° (-6.14° ± 1.60°, P < .001). ACL-ALSR also overconstrained the knee at 60° (-3.65° ± 1.90°, P < .001) and 90° (-3.18° ± 2.53°, P < .001). For a simulated pivot-shift test, both combined procedures significantly reduced the ACLR instability, with anterolateral translation and internal rotation being overconstrained in ACLR+LET at 30° (-3.32 mm ± 3.89 mm, P = .005; -2.58° ± 1.61°, P < .001) and 45° (-3.02 mm ± 3.95 mm, P = .012; -3.44° ± 2.86°, P < .001). However, the ACL-ALSR overconstrained only the anterolateral translation at 30° (-1.51 mm ± 2.39 mm, P = .046) and internal rotation at 45° (-2.09° ± 1.70°, P < .001). There were no significant differences between the two combined procedures at most testing degrees in each testing state, except for the internal rotation at 30° (P = .007) and 90° (P = .032) in internal rotation torque. CONCLUSION: ACL reconstruction alone did not restore intact knee kinematics in knees with concurrent ACL tears and severe ALS injury (ACL-ALS-deficient status). Both ACL-ALSR and ACLR+LET procedures restored knee stability at some flexion degrees, with less overconstraints in internal rotation resulting from ACL-ALSR. CLINICAL RELEVANCE: For patients with combined ACL tears and severe ALS deficiency, isolated ACLR probably results in residual rotational and pivot-shift instability. Both ACL-ALSR and ACLR+LET show promise for the improvement of knee stability, whereas ACL-ALSR has less propensity for knee overconstraint.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 779-782, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365624

RESUMO

OBJECTIVE: To explore the genetic basis for a child with febrile seizures. METHODS: Peripheral venous blood samples were taken from the child and his parents for the analysis of chromosomal karyotype and dynamic variant of the FMR1 gene. The family trio was also subjected to target capture and next generation sequencing (NGS) with a gene panel related to developmental retardation, mental retardation, language retardation, epilepsy and special facial features. RESULTS: The child was found to have a normal karyotype by conventional cytogenetic analysis (400 bands). No abnormal expansion was found with the CGG repeats of the FMR1 gene. NGS revealed that the child has carried a heterozygous c.864+1 delG variant of the MEF2C gene, which may lead to abnormal splicing and affect its protein function. The same variant was found in neither parent, suggesting that it has a de novo origin. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.864+1delG variant of MEF2C gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: MEF2C, as the key gene for chromosome 5q14.3 deletion syndrome which was speculated as a cause for febrile seizures, has an autosomal dominant effect. The c.864+1delG variant of the MEF2C gene may account for the febrile seizures in this patient.


Assuntos
Transtornos Cromossômicos , Epilepsia , Deficiência Intelectual , Criança , Deleção Cromossômica , Proteína do X Frágil de Retardo Mental , Humanos , Deficiência Intelectual/genética , Cariotipagem , Fatores de Transcrição MEF2/genética
16.
Medicine (Baltimore) ; 100(29): e26724, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398046

RESUMO

ABSTRACT: To evaluate the duration of topical brimonidine therapy before the onset of brimonidine-related allergic conjunctivitis and the clinical characteristics associated with the development of brimonidine allergy.We retrospectively enrolled patients who presented brimonidine allergy from December 1, 2008 to November 30, 2020. The duration of brimonidine treatment, concomitant medications, benzalkonium chloride (BAK) exposure, change in IOP, and season of onset were evaluated.292 patients were included, among which 147 were female and 145 were male. The mean age was 58.3 ± 13.6 years old. The mean (median) duration of brimonidine therapy was 266.6 (196) days, with a peak at 60-120 days. The duration was similar whether the patients received brimonidine monotreatment or in combination with other glaucoma drugs, with or without BAK. The IOP increased by 5.6% after brimonidine allergy (P < .001), which was even higher in the brimonidine monotherapy group (9.2%, P < .001). There was no significant IOP elevation in patients treated with multiple glaucoma medications.Around half of brimonidine allergy occurred within 6 months, with a peak in 2 to 4 months. The duration did not differ in patients receiving brimonidine monotherapy or multiple glaucoma medications. The presence of BAK did not affect the duration either. When brimonidine allergy occurred, there was a loss of IOP control, especially in patients receiving brimonidine monotherapy. It is recommended to switch to other types of glaucoma medications for better IOP control.


Assuntos
Anti-Hipertensivos/efeitos adversos , Tartarato de Brimonidina/efeitos adversos , Conjuntivite Alérgica/epidemiologia , Soluções Oftálmicas/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Tartarato de Brimonidina/administração & dosagem , Conjuntivite Alérgica/induzido quimicamente , Esquema de Medicação , Feminino , Seguimentos , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Estudos Retrospectivos
17.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360807

RESUMO

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF--5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal-epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células CACO-2 , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Células HCT116 , Humanos , Polissacarídeos/farmacologia
18.
J Orthop Surg Res ; 16(1): 480, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34364374

RESUMO

INTRODUCTION: The role of open cerclage wiring in comminuted femoral shaft fracture treatment with intramedullary nails remains unclear. Here, we analyzed the effect of open cerclage wiring and the risk factors for nonunion after interlocking nailing in comminuted femoral shaft fracture treatment. We hypothesized that open cerclage wiring can be applied in patients with severe comminuted femoral shaft fractures without affecting bone healing. PATIENTS AND METHODS: This retrospective cohort study used data from consecutive patients who underwent interlocking nail fixation of a comminuted femoral shaft fracture between January 1, 2009, and December 31, 2016. First, eligible patients were divided into the wire and no wire groups according to the surgical technique used, and their union rate was recorded. The patients were then divided into the union and nonunion groups, and their perioperative data were analyzed. RESULTS: In total, 71 comminuted femoral shaft fractures treated with interlocking nail fixation were included: 38 fractures (53.5%) augmented with the open wiring technique and 33 reduced with closed or mini-open techniques without wiring. The wire group demonstrated significant improvements in fracture reduction compared with the no wire group, whereas no significant difference was observed in the union rate between the wire and no wire groups (p = 0.180). Moreover, 46 (65%) of 71 fractures achieved union smoothly, and no significant difference was observed in any perioperative data between the union and nonunion groups. DISCUSSION: Augmentation with open cerclage wiring is indicated for comminuted femoral shaft fractures treated with intramedullary nails, even when the fragments are large or greatly displaced. Thus, open cerclage wiring can be used for fracture treatment without decreasing the union rate.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34333150

RESUMO

BACKGROUND & AIMS: Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS: The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). RESULTS: The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS: Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

20.
J Neurosci ; 41(38): 7942-7953, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34380760

RESUMO

Microglia maintain brain health and play important roles in disease and injury. Despite the known ability of microglia to proliferate, the precise nature of the population or populations capable of generating new microglia in the adult brain remains controversial. We identified Prominin-1 (Prom1; also known as CD133) as a putative cell surface marker of committed brain myeloid progenitor cells. We demonstrate that Prom1-expressing cells isolated from mixed cortical cultures will generate new microglia in vitro To determine whether Prom1-expressing cells generate new microglia in vivo, we used tamoxifen inducible fate mapping in male and female mice. Induction of Cre recombinase activity at 10 weeks in Prom1-expressing cells leads to the expression of TdTomato in all Prom1-expressing progenitors and newly generated daughter cells. We observed a population of new TdTomato-expressing microglia at 6 months of age that increased in size at 9 months. When microglia proliferation was induced using a transient ischemia/reperfusion paradigm, little proliferation from the Prom1-expressing progenitors was observed with the majority of new microglia derived from Prom1-negative cells. Together, these findings reveal that Prom1-expressing myeloid progenitor cells contribute to the generation of new microglia both in vitro and in vivo Furthermore, these findings demonstrate the existence of an undifferentiated myeloid progenitor population in the adult mouse brain that expresses Prom1. We conclude that Prom1-expressing myeloid progenitors contribute to new microglia genesis in the uninjured brain but not in response to ischemia/reperfusion.SIGNIFICANCE STATEMENT Microglia, the innate immune cells of the CNS, can divide to slowly generate new microglia throughout life. Newly generated microglia may influence inflammatory responses to injury or neurodegeneration. However, the origins of the new microglia in the brain have been controversial. Our research demonstrates that some newly born microglia in a healthy brain are derived from cells that express the stem cell marker Prominin-1. This is the first time Prominin-1 cells are shown to generate microglia.

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