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1.
Mol Cell ; 82(8): 1528-1542.e10, 2022 04 21.
Article in English | MEDLINE | ID: mdl-35245436

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is a global health concern with no approved drugs. High-protein dietary intervention is currently the most effective treatment. However, its underlying mechanism is unknown. Here, using Drosophila oenocytes, the specialized hepatocyte-like cells, we find that dietary essential amino acids ameliorate hepatic steatosis by inducing polyubiquitination of Plin2, a lipid droplet-stabilizing protein. Leucine and isoleucine, two branched-chain essential amino acids, strongly bind to and activate the E3 ubiquitin ligase Ubr1, targeting Plin2 for degradation. We further show that the amino acid-induced Ubr1 activity is necessary to prevent steatosis in mouse livers and cultured human hepatocytes, providing molecular insight into the anti-NAFLD effects of dietary protein/amino acids. Importantly, split-intein-mediated trans-splicing expression of constitutively active UBR2, an Ubr1 family member, significantly ameliorates obesity-induced and high fat diet-induced hepatic steatosis in mice. Together, our results highlight activation of Ubr1 family proteins as a promising strategy in NAFLD treatment.


Subject(s)
Non-alcoholic Fatty Liver Disease , Amino Acids, Essential/metabolism , Amino Acids, Essential/pharmacology , Amino Acids, Essential/therapeutic use , Animals , Diet, High-Fat/adverse effects , Hepatocytes/metabolism , Liver/metabolism , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/prevention & control , Ubiquitination
2.
Plant J ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39283979

ABSTRACT

The pairing and synapsis of homologous chromosomes are crucial for their correct segregation during meiosis. The LINC (Linker of Nucleoskeleton and Cytoskeleton) complex can recruit kinesin protein at the nuclear envelope, affecting telomere bouquet formation and homologous pairing. Kinesin-1-like protein Pollen Semi-Sterility1 (PSS1) plays a pivotal role in male meiotic chromosomal behavior and is essential for fertility in rice. However, its exact role in meiosis, especially as kinesin involved in homologous pairing and synapsis, has not been fully elucidated. Here, we generated three pss1 mutants by genome editing technology to dissect PSS1 biological functions in meiosis. The pss1 mutants exhibit alterations in the radial microtubule organization at pachytene and manifest a deficiency in telomere clustering, which is critical for full-length homologous pairing. We reveal that PSS1 serves as a key mediator between chromosomes and cytoskeleton, thereby regulating microtubule organization and transmitting the force to nuclei to facilitate homologous chromosome pairing and synapsis in meiosis.

3.
J Lipid Res ; 65(10): 100635, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39187042

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. If left untreated, MASLD can progress from simple hepatic steatosis to metabolic dysfunction-associated steatohepatitis, which is characterized by inflammation and fibrosis. Current treatment options for MASLD remain limited, leaving substantial unmet medical needs for innovative therapeutic approaches. Here, we show that PLIN2, a lipid droplet protein inhibiting hepatic lipolysis, serves as a promising therapeutic target for MASLD. Hepatic PLIN2 levels were markedly elevated in multiple MASLD mouse models induced by diverse nutritional and genetic factors. The liver-specific deletion of Plin2 exhibited significant anti-MASLD effects in these models. To translate this discovery into a therapeutic application, we developed a GalNAc-siRNA conjugate with enhanced stabilization chemistry and validated its potent and sustained efficacy in suppressing Plin2 expression in mouse livers. This siRNA therapeutic, named GalNAc-siPlin2, was shown to be biosafe in mice. Treatment with GalNAc-siPlin2 for 6-8 weeks led to a decrease in hepatic triglyceride levels by approximately 60% in high-fat diet- and obesity-induced MASLD mouse models, accompanied with increased hepatic secretion of VLDL-triglyceride and enhanced thermogenesis in brown adipose tissues. Eight-week treatment with GalNAc-siPlin2 significantly improved hepatic steatosis, inflammation, and fibrosis in high-fat/high fructose-induced metabolic dysfunction-associated steatohepatitis models compared to control group. As a proof of concept, we developed a GalNAc-siRNA therapeutic targeting human PLIN2, which effectively suppressed hepatic PLIN2 expression and ameliorated MASLD in humanized PLIN2 knockin mice. Together, our results highlight the potential of GalNAc-siPLIN2 as a candidate MASLD therapeutic for clinical trials.

4.
Ecol Lett ; 27(6): e14446, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38814284

ABSTRACT

Grime's competitive, stress-tolerant, ruderal (CSR) theory predicts a shift in plant communities from ruderal to stress-tolerant strategies during secondary succession. However, this fundamental tenet lacks empirical validation using long-term continuous successional data. Utilizing a 60-year longitudinal data of old-field succession, we investigated the community-level dynamics of plant strategies over time. Our findings reveal that while plant communities generally transitioned from ruderal to stress-tolerant strategies during succession, initial abandonment conditions crucially shaped early successional strategies, leading to varied strategy trajectories across different fields. Furthermore, we found a notable divergence in the CSR strategies of alien and native species over succession. Initially, alien and native species exhibited similar ruderal strategies, but in later stages, alien species exhibited higher ruderal and lower stress tolerance compared to native species. Overall, our findings underscore the applicability of Grime's predictions regarding temporal shifts in CSR strategies depending on both initial community conditions and species origin.


Subject(s)
Introduced Species , Plants , Plant Physiological Phenomena , Stress, Physiological , Ecosystem , Models, Biological , Plant Development
5.
Molecules ; 29(17)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39274962

ABSTRACT

Teicoplanin has been banned in the veterinary field due to the drug resistance of antibiotics. However, teicoplanin residue from the antibiotic abuse of humans and animals poses a threat to people's health. Therefore, it is necessary to develop an efficient way for the highly accurate and reliable detection of teicoplanin from humans, food, and water. In this study, novel imprinted quantum dots of teicoplanin were prepared based on boronate affinity-based precisely controlled surface imprinting. The imprinting factor (IF) for teicoplanin was evaluated and reached a high value of 6.51. The results showed excellent sensitivity and selectivity towards teicoplanin. The relative fluorescence intensity was inversely proportional to the concentration of teicoplanin, in the range of 1.0-17 µM. And its limit of detection (LOD) was obtained as 0.714 µM. The fluorescence quenching process was mainly controlled by a static quenching mechanism via the non-radiative electron-transfer process between QDs and the five-membered cyclic boronate esters. The recoveries for the spiked urine, milk, and water samples ranged from 95.33 to 104.17%, 91.83 to 97.33, and 94.22 to 106.67%, respectively.


Subject(s)
Anti-Bacterial Agents , Boronic Acids , Quantum Dots , Teicoplanin , Quantum Dots/chemistry , Humans , Teicoplanin/chemistry , Teicoplanin/analysis , Boronic Acids/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Spectrometry, Fluorescence/methods , Limit of Detection , Water/chemistry , Molecular Imprinting/methods , Esters/chemistry , Esters/analysis , Electron Transport , Food Contamination/analysis , Food Analysis/methods , Animals , Biosensing Techniques/methods , Milk/chemistry , Fluorescence
6.
Anal Chem ; 95(32): 12032-12038, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37542454

ABSTRACT

A DNA/RNA biosensor capable of single nucleotide variation (SNV) resolution is highly desirable for drug design and disease diagnosis. To meet the point-of-care demand, rapid, cost-effective, and accurate SNV detection is of great significance but still suffers from a challenge. In this work, a unique nonenzymatic dual-modal (multicolorimetric and photothermal) visualization DNA biosensor is first proposed for SNV identification on the basis of an entropy-driven nanomachine with double output DNAs and coordination etching of anisotropic silver triangular nanoplates (Ag TNPs). When the target initiates the DNA nanomachine, the liberated multiple output DNAs can be utilized as a bridge to produce a superparamagnetic sandwich complex. The incoming poly-C DNA can coordinate and etch highly active Ag+ ions at the tips of Ag TNPs, causing a shift in the plasmon peak of Ag TNPs from 808 to 613 nm. The more target DNAs are introduced, the more output DNAs are released and thus the more Ag+ ions are etched. The noticeable color changes of anisotropic Ag TNPs can be differentiated by "naked eye" and accurate temperature reading. The programmable DNA nanotechnology and magnetic extraction grant the high specificity. Also, the SNV detection results can be self-verified by the two-signal readouts. Moreover, the dual-modal biosensor has the advantages of portability, cost-effectiveness, and simplicity. Particularly, the exclusive entropy-driven amplifier liberates double output DNAs to bridge more poly-C DNAs, enabling the dual-modal visualization DNA biosensor with improved sensitivity.


Subject(s)
Biosensing Techniques , Metal Nanoparticles , Silver , Colorimetry/methods , Entropy , Biosensing Techniques/methods , DNA
7.
Acta Biochim Biophys Sin (Shanghai) ; 55(5): 783-794, 2023 May 25.
Article in English | MEDLINE | ID: mdl-37232573

ABSTRACT

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes are a promising therapeutic agent for human disease, but their effects on neural stem cells (NSCs) subject to spinal cord ischaemia-reperfusion injury (SCIRI) remain unknown. Here, we examine the impact of miR-199a-5p-enriched exosomes derived from BMSCs on NSC proliferation. We establish a rat model of aortic cross-clamping to induce SCIRI in vivo and a primary NSC model of oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate SCIRI in vitro. CCK8, EdU, and BrdU assays are performed to evaluate the proliferation of NSCs. Hematoxylin and eosin (H&E) staining is used to determine the number of surviving neurons. The Basso, Beattie, and Bresnahan (BBB) scale and inclined plane test (IPT) are used to evaluate hind limb motor function. DiO-labelled exosomes are efficiently internalized by NSCs and increase ectopic amounts of miR-199a-5p, which promotes the proliferation of NSCs. In contrast, exosomes derived from miR-199a-5p-depleted BMSCs exert fewer beneficial effects. MiR-199a-5p targets and negatively regulates glycogen synthase kinase 3ß (GSK-3ß) and increases nuclear ß-catenin and cyclin D1 levels. miR-199a-5p inhibition reduces the total number of EdU-positive NSCs after OGD/R, but the GSK-3ß inhibitor CHIR-99021 reverses this effect. In vivo, intrathecal injection of BMSC-derived exosomes increases the proliferation of endogenous spinal cord NSCs after SCIRI. In addition, more proliferating NSCs are found in rats intrathecally injected with exosomes overexpressing miR-199a-5p. In summary, miR-199a-5p in BMSC-derived exosomes promotes NSC proliferation via GSK-3ß/ß-catenin signaling.


Subject(s)
Exosomes , Mesenchymal Stem Cells , MicroRNAs , Neural Stem Cells , Reperfusion Injury , Rats , Humans , Animals , MicroRNAs/genetics , beta Catenin/genetics , Glycogen Synthase Kinase 3 beta/genetics , Exosomes/genetics , Cell Proliferation
8.
Molecules ; 28(3)2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36770710

ABSTRACT

The therapeutic efficacy of nanoscale drug delivery systems is related to particle size, zeta potential, morphology, and other physicochemical properties. The structure and composition of nanocarriers may affect their physicochemical properties. To systematically evaluate these characteristics, three analogues, namely polyethylene glycol (PEG), PEG-conjugated octadecylamine (PEG-C18), and tri(ethylene glycol) (TEG), were explored as nanocarriers to entrap celastrol (CSL) via the injection-combined dialysis method. CSL nanoparticles were successfully prepared as orange milky solutions, which revealed a similar particle size of approximately 120 nm, with narrow distribution and a negative zeta potential of -20 mV. All these CSL nanoparticles exhibited good storage stability and media stability but presented different drug-loading capacities (DLCs), release profiles, cytotoxicity, and hemolytic activity. For DLCs, PEG-C18/CSL exhibited better CSL entrapment capacity. Regarding the release profiles, TEG/CSL showed the lowest release rate, PEG-C18/CSL presented a moderate release rate, and PEG/CSL exhibited a relatively fast release rate. Based on the different release rates, PEG-C18/CSL and TEG/CSL showed higher degrees of cytotoxicity than PEG/CSL. Furthermore, TEG/CSL showed the lowest membrane toxicity, and its hemolytic rate was below 20%. These results suggest that the structural effects of nanocarriers can affect the interactions between nanocarriers and drugs, resulting in different release profiles and antitumor activity.


Subject(s)
Nanoparticles , Renal Dialysis , Drug Delivery Systems/methods , Pentacyclic Triterpenes , Polyethylene Glycols/chemistry , Pharmaceutical Preparations , Nanoparticles/chemistry , Drug Carriers/chemistry , Particle Size
9.
Macromol Rapid Commun ; 43(5): e2100736, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34837422

ABSTRACT

Nano- and microscale morphology endows surfaces that play conspicuous roles in natural or artificial objects with unique functions. Surfaces with dynamic regulating features capable of switching the structures, patterns, and even dimensions of their surface profiles can control friction and wettability, thus having potential applications in antibacterial, haptics, and fluid dynamics. Here, a freestanding film with light-switchable surface based on cholesteric liquid crystal networks is presented to translate 2D flat plane into a 3D nanometer-scale topography. The wettability of the interface can be controlled by hiding or revealing the geometrical features of the surfaces with light. This reversible dynamic actuation is obtained through the order parameter change of the periodic cholesteric organization under a photoalignment procedure and lithography-free mode. Complex tailored structures can be used to encrypt tactile information and improve wettability by predesigning the orientation distribution of liquid crystal director. This rapid switching nanoprecision smart surface provides a novel platform for artificial skin, optics, and functional coatings.


Subject(s)
Liquid Crystals , Liquid Crystals/chemistry , Wettability
10.
Nurs Health Sci ; 24(3): 625-633, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35670524

ABSTRACT

Chronic hepatitis B (CHB) is a prevalent disease with various negative consequences. The lived experience of coping and recovery of a patient with Chronic hepatitis B was explored in this study. A semistructured interview was conducted with one participant who had been recovered from Chronic hepatitis B for 10 years. Data were analyzed using interpretative phenomenological analysis. Five superordinate themes emerged, including lingering in the shadow of death anxiety, diminished functioning of the self, adopting a highly disciplined lifestyle, receiving social support, and the return of the self with scars. The findings revealed that the disease is deeply associated with moral standing, which means the diagnosis of Chronic hepatitis B might imply a loss of moral face for Chinese people living with the condition. Our findings point to the need for increasing knowledge about chronic hepatitis B, decoupling the disease from a moral standpoint, and providing a supportive environment.


Subject(s)
Hepatitis B, Chronic , Adaptation, Psychological , China , Hepatitis B, Chronic/complications , Humans , Social Support
11.
J Environ Sci (China) ; 121: 211-223, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35654511

ABSTRACT

To relieve dust pollution in open cut coal mines and reduce the hazards of coal dust pollution to the environment and workers we optimized the synthesis of a dust suppressant by graft copolymerization of environmentally friendly soy protein isolate with methyl methacrylate. This dust suppressant could effectively control dust pollution in open cut coal mines. The optimized conditions for graft copolymerization in this case were determined by a response surface experiment designed with Design-Expert 10 software. Characterization by scanning electron microscopy showed a significant morphology change of the dust suppressant and the generation of a rigid and dense layer on its surface after interacting with coal dust. The layer exhibited good bonding and dust suppression performance. The analysis with Fourier-transform infrared spectroscopy revealed the appearance of new absorption peaks near 1300, 1072, and 1631 cm-1, demonstrating effective graft copolymerization. The proposed dust suppressant exhibited excellent wind erosion resistance, with a resistance that exceeded 90% at a wind speed of 6.5 m/sec. The successful graft copolymerization and effective bonding and curing of the dust suppressant on coal dust were experimentally verified. This is of great significance to the control of coal dust pollution.


Subject(s)
Air Pollution , Coal Mining , Occupational Exposure , Coal , Dust/analysis , Humans , Minerals , Occupational Exposure/analysis
12.
Anal Chem ; 93(31): 11043-11051, 2021 08 10.
Article in English | MEDLINE | ID: mdl-34319082

ABSTRACT

DNA circuits as one of the dynamic nanostructures can be rationally designed and show amazing geometrical complexity and nanoscale accuracy, which are becoming increasingly attractive for DNA entropy-driven amplifier design. Herein, a novel and elegant exciton-plasmon interaction (EPI)-based photoelectrochemical (PEC) biosensor was developed with the assistance of a programmable entropy-driven DNA amplifier and superparamagnetic nanostructures. Low-abundance miRNA-let-7a as a model can efficiently initiate the operation of the entropy-driven DNA amplifier, and the released output DNAs can open the partially hybridized double-stranded DNA anchored on Fe3O4@SiO2 particles. The liberated Au nanoparticles (NPs)-cDNA can completely hybridize with CdSe/ZnS quantum dots (QDs)-cDNA-1 and result in proportionally decreased photocurrent of CdSe/ZnS QDs-cDNA-1. This unique entropy-driven amplification strategy is beneficial for reducing the reversibility of each step reaction, enables the base sequence invariant and the reaction efficiency improvement, and exhibits high thermal stability and specificity as well as flexible design. These features grant the PEC biosensor with ultrasensitivity and high selectivity. Also, instead of solid-liquid interface assembly for conventional EPI-based PEC biosensors, herein, DNA hybridization in the solution phase enables the improved hybridization efficiency and sensitivity. In addition, superparamagnetic Fe3O4@SiO2 particles further ensure the enhancement of the selectivity and reliability of the as-designed PEC biosensor. Particularly, this single-step electrode modification procedure evidently improves the electrode fabrication efficiency, reproducibility, and stability.


Subject(s)
Biosensing Techniques , Cadmium Compounds , Metal Nanoparticles , Quantum Dots , DNA , Electrochemical Techniques , Gold , Reproducibility of Results , Silicon Dioxide
13.
Am J Otolaryngol ; 42(6): 103148, 2021.
Article in English | MEDLINE | ID: mdl-34214711

ABSTRACT

BACKGROUND: The anti-angiogenic agent bevacizumab is currently the only drug used clinically for neurofibromatosis type 2-related vestibular schwannomas (NF2-VS). Though benefits have been demonstrated in several cases, the standardized dosage remains unclear. OBJECTIVE: Our meta-analysis was performed to systematically and comprehensively investigate the reliability and toxicity of bevacizumab in the treatment of NF2-VS, with particular emphasis on the impact of dosage. METHODS: The literature search was conducted for studies providing data on patients treated with bevacizumab for NF2-VS across PubMed, Embase, and Cochrane Library until December 31, 2020. Two reviewers extracted the incidence rate of results independently. Then we calculated and pooled unadjusted incidence rate with 95% CIs for each study. The subgroups analyzed were conducted. RESULTS: Fourteen citations (prospective or retrospective observational cohort studies) were eligible based on data from a total of 247 patients with NF2 and 332 related VSs. The pooled results showed that the radiographic response rate (RRR) was 30% [95% CI (20%-42%)], the hearing response rate (HRR) was 32% [95% CI (21%-45%)]. The incidence of major complications was: hypertension 29% [95% CI (23%-35%)], proteinuria 30% [95% CI (18%-44%)], menstrual disorders 44% [95% CI (16%-73%)], hemorrhage 14% [95% CI (4%-26%)], grade3/4 events 12% [95% CI (4%-22%)]. CONCLUSIONS: Nearly one-third of NF2-VS patients may benefit significantly from bevacizumab due to hearing improvement and tumor reduction. Menstrual disorders were the most common adverse events. The high-dose regimen didn't show better efficacy, but results varied considerably according to age.


Subject(s)
Bevacizumab/administration & dosage , Bevacizumab/toxicity , Neurofibromatosis 2/drug therapy , Neuroma, Acoustic/drug therapy , Vestibulocochlear Nerve , Adult , Age Factors , Bevacizumab/adverse effects , Dose-Response Relationship, Drug , Female , Hearing , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Hypertension/chemically induced , Hypertension/epidemiology , Male , Menstruation Disturbances/chemically induced , Menstruation Disturbances/epidemiology , Neurofibromatosis 2/diagnostic imaging , Neurofibromatosis 2/physiopathology , Neuroma, Acoustic/diagnostic imaging , Neuroma, Acoustic/physiopathology , Prospective Studies , Proteinuria/chemically induced , Proteinuria/epidemiology , Retrospective Studies , Young Adult
14.
Opt Express ; 28(19): 27676-27687, 2020 Sep 14.
Article in English | MEDLINE | ID: mdl-32988056

ABSTRACT

A liquid crystal elastomer (LCE) film is successfully deposited with a terahertz metamaterial using thermal evaporation via a programmed electronic shutter and high-efficiency cooling system. The transmittance of the metamaterial at its resonance frequency is monotonically increased from 0.0036 to 1.0 as a pump beam bends the LCE film, so the metamaterial has a large switching contrast of 277 at the frequency. The monotonic increase in the resonance transmittance arises from the constant resonance frequency of the metamaterial at the transmittance modulation and depicts that the metamaterial-deposited LCE film can continuously tune the transmitted intensity of a terahertz beam. The metamaterial-deposited LCE film has potential in developing continuously tunable intensity modulators with large switching contrasts for the application of terahertz imaging and terahertz communication. Therefore, the thermal evaporation expands the application of metamaterials and improves their optical properties.

15.
Molecules ; 24(10)2019 May 27.
Article in English | MEDLINE | ID: mdl-31137776

ABSTRACT

Cyanine dyes have been widely applied in various biological systems owing to their specific photochemical properties. Assembly and disassembly process of cyanine dyes were constructed and regulated by special biomolecules. In this paper, dimeric cyanine dyes with different repeat units (oligo-oxyethylene) in linker (TC-Pn) (n = 3-6) were found to form H-aggregates or mixture aggregates in PBS. These aggregates could be disassembled into dimer and/or monomer by (TGnT) tetramolecular G-quadruplexes (n = 3-6, 8), which were affected by the linker length of dimeric cyanine dyes and layers of G-quartets. The 1H-NMR titration results suggest that the binding mode of dimeric cyanine dye with TGnT might be on both ends-stacking like a clip. This binding mode could clearly explain that matching structures between dimeric cyanine dyes and TGnT quadruplexes could regulate the disassembly properties of aggregates. These results could provide clues for the development of highly specific G-quadruplex probes.


Subject(s)
Carbocyanines/chemistry , Dimerization , G-Quadruplexes , Dimethyl Sulfoxide/chemistry , Proton Magnetic Resonance Spectroscopy
16.
Horm Metab Res ; 50(10): 768-777, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30261527

ABSTRACT

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors are both novel and second-line therapies in type 2 diabetes mellitus, yet no well-rounded comparison of these two drugs has been published. Upon searching randomized controlled trials in databases from inception to July 2018, we collected studies on the efficacy or safety of SGLT-2 inhibitors compared with those of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. A total of 12 randomized controlled studies including 4342 patients were included in this meta-analysis. Compared with DPP-4 inhibitors, SGLT-2 inhibitors achieved greater reductions in HbA1c (SMD -0.22; 95% CI: -0.30, -0.14; p=0.000) and fasting plasma glucose (SMD -0.48; 95% CI: -0.56, -0.41; p=0.000). In addition, these reductions increased with a prolonged treatment duration from 12 to 78 weeks. Geographically, significant reductions of SGLT-2 inhibitors in HbA1c and FPG were found in North America and Europe, but not in Asia. Furthermore, SGLT-2 inhibitors showed greater reductions in body weight (SMD -0.72; 95% CI: -0.81, -0.63; p=0.000) from baseline, with an increased incidence of genital infections (OR 4.49; 95% CI: 2.96, 6.83; p=0.000) and pollakiuria (OR 2.24; 95% CI: 1.05, 4.79; p=0.037) and a decreased incidence of hypertension and hyperglycemia. Overall, the current meta-analysis demonstrated that compared to DPP-4 inhibitors, SGLT-2 inhibitors have beneficial effects on HbA1c, FPG, body weight, SBP, DBP, and HDL-cholesterol in patients with type 2 diabetes. However, SGLT-2 inhibitors are associated with increased total cholesterol and LDL-cholesterol and a higher incidence of genital infections and pollakiuria.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Fasting/blood , Glycated Hemoglobin/metabolism , Humans , Publication Bias , Treatment Outcome
17.
Br J Neurosurg ; 32(5): 479-483, 2018 08 27.
Article in English | MEDLINE | ID: mdl-30146911

ABSTRACT

BACKGROUND: Surgical approaches for Chiari malformation type I (CM-I) complicated with syringomyelia (SM) are controversial, so we assessed the efficacy and safety of two widely used procedures. METHODS: We retrospectively analyzed results from posterior fossa decompression (PFD) using bony decompression with dura-splitting or a combined technique (duraplasty with arachnoid dissection and coagulation of the herniated tonsils) for CM-I associated with SM between Jan 2008 and Feb 2016. Patients were followed up for at least one year. General data, primary outcomes (symptom improvement, syrinx reductions, and complications) and secondary outcomes (operating time, blood loss, postoperative hospital stay) for each procedure were compared. RESULTS: Of the 49 patients treated, 17 had dura-splitting decompression and 32 had the combined technique. There were no significant differences in general data. The combined technique was significantly superior to dura-splitting for long-term syrinx reductions (length, 100.03 ± 44.79 vs 72.73 ± 34.79 mm, p = 0.040; diameter, 8.09 ± 3.46 vs 5.73 ± 3.02 mm, p = 0.026) and symptom improvement (75.00% vs 47.06%, p = 0.036). No postoperative complications occurred during dura-splitting cases; however, complications occurred in 9 combined technique cases (31.25%, p = 0.010) and surgical time was longer for the combined technique (248.03 ± 60.12 vs 167.94 ± 60.11 min, p < 0.001). CONCLUSIONS: The combined technique improved long-term symptoms and reduced syringes compared to dura-splitting; however, postoperative complications are more likely.

18.
Analyst ; 142(9): 1536-1544, 2017 May 02.
Article in English | MEDLINE | ID: mdl-28368059

ABSTRACT

Mono- and bis-rhodamine derivatives appended with amino (RhB1) and imino (BRI) groups, respectively, have been designed as colorimetric and fluorescent sensors for the selective detection of Pd2+. In addition, an attempt has been made to improve the water solubility of the probe by synthesizing inclusion complexes of RhB1 with ß-cyclodextrin as the host molecule. The resulting probe, RhB1-CD, exhibited exactly the same physicochemical phenomena as the guest molecule RhB1, indicating that complexation with ß-CD improved the water solubility of RhB1 without affecting its sensing ability. With increasing concentrations of Pd2+, the absorption (556 nm) and emission (591 nm) intensities of BRI as well as the absorption intensities of RhB1/RhB1-CD (563 nm) increase, whereas the emission intensities of RhB1/RhB1-CD decrease due to fluorescence quenching. Therefore, BRI can act as an "OFF-ON" fluorescent probe switch in CH3CN/H2O (3 : 2 v/v) with a detection limit of 1 µM in solution, whereas RhB1 and RhB1-CD act as "ON-OFF" fluorescent probes in EtOH/H2O (1 : 1 v/v) and water, respectively, with a detection limit of 10 µM. All these probes exhibited high selectivity for Pd2+ and reversibility by treatment with Na2S. In the presence of commonly coexisting metal ions, such as Hg2+, Fe3+, Cu2+ and Al3+, BRI undergoes either catalytic Schiff base hydrolysis or it is unaffected by its affinity to the metal ions. However, Pd2+ can be effectively distinguished by a 12-15 nm bathochromic shift in its emission spectrum when compared with that of other metal ions. A Job's plot revealed that BRI forms 1 : 2 complexes by a spirolactam ring opening mechanism, whereas RhB1/RhB1-CD form 2 : 1 complexes by a ring opening mechanism followed by Pd2+-induced dimerization; the proposed binding mechanisms are presented.


Subject(s)
Fluorescent Dyes/chemistry , Rhodamines/chemistry , beta-Cyclodextrins/chemistry , Solubility , Spectrometry, Fluorescence
19.
Eur Radiol ; 26(8): 2740-8, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26597544

ABSTRACT

OBJECTIVES: To retrospectively evaluate short linear shadows connecting pulmonary segmental arteries to oblique fissures in thin-section CT images and determine their anatomical basis. METHODS: CT scanning was performed on 108 patients and 11 lung specimens with no lung diseases around the oblique fissures or hila. Two radiologists evaluated the imaging. The parameters included length, thickness of short linear shadows, pulmonary segmental artery variations, and traction interlobar fissures, etc. RESULTS: The short linear shadows were not related to sex, age, or smoking history. The lengths of the short linear shadows were generally within 10 mm. The thicknesses of the short linear shadows ranged from 1 to 2 mm. Of the patients, 26.9 % showed pulmonary segmental artery variations; 66.7 % of short linear shadows pulled oblique fissures. In three-dimensional images, the short linear shadows appeared as arc planes, with one side edge connected to the oblique fissure, one side edge connected to a pulmonary segmental artery. On the tissue slices, the short linear shadow exhibited a band structure composed of connective tissues, small blood vessels, and small lymphatic vessels. CONCLUSIONS: Short linear shadows are a type of normal intrapulmonary membranes and can maintain the integrity of the oblique fissures and hilar structure. KEY POINTS: • Volumetric thin-section CT scanning is commonly used to study lung anatomy. • Short linear shadows are a common intrapulmonary structure in thin-section CT. • Short linear shadows correlate with band structures on the correlative tissue slices.


Subject(s)
Cone-Beam Computed Tomography/methods , Imaging, Three-Dimensional/methods , Lung Diseases/diagnosis , Lung/diagnostic imaging , Pulmonary Artery/diagnostic imaging , Tomography, Spiral Computed/methods , X-Ray Microtomography/methods , Adult , Aged , Aged, 80 and over , Biopsy , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Young Adult
20.
J Nanosci Nanotechnol ; 15(12): 9834-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26682421

ABSTRACT

Capsaicin is recognized as a natural tumor preventive compound and exhibits a remarkable anticancer action. Strong inhibitory role of capsaicin on gliomas has been well documented. However, the use of capsaicin is limited due to its hydrophobicity, low affinity, and short half-life. The present study aimed to explore the physiochemical characteristics of the capsaicin-loading nanoparticles prepared by methoxy polyethylene glycol-poly(caprolactone) (mPEG-PCL) amphiphilic block copolymer. It also aimed to evaluate the ability of the nanoparticles to cross the blood-brain barrier. Additionally, the uptake of nanoparticles in the glioma cells and its ability to inhibit cell proliferation were tested in human glioblastoma U251 cells. mPEG-PCL amphiphilic block copolymer was synthesized using the ring-opening polymerization method, and the capsaicin-loading nanoparticles were prepared with the solvent diffusion method. In vitro drug release assay revealed that the capsaicin-loading nanoparticles presented a slow-release characteristic. Coculture of the human glioblastoma U251 cells and the fluorescein-loading nanoparticles showed the uptake of nanoparticles in U251 cells by endocytosis. We found that the NIR-797 isothiocyanate-loading nanoparticles can cross the blood-brain barrier. In addition, the capsaicin-loading nanoparticle showed a remarkable inhibition on the growth of U251 cells. The efficacy of the capsaicin-loading nanoparticles against tumor cells was significantly superior to the capsaicin at low concentrations. It is concluded that the capsaicin-loading nanoparticles can provide an extremely promising approach for chemotherapy of gliomas.


Subject(s)
Capsaicin/pharmacology , Drug Carriers/chemistry , Glioma/drug therapy , Nanoparticles/chemistry , Cell Line, Tumor , Drug Liberation , Glioblastoma/drug therapy , Humans , Particle Size , Polyesters/chemistry , Polyethylene Glycols/chemistry
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