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1.
Arch Oral Biol ; 109: 104588, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669922

RESUMO

OBJECTIVE: Dental occlusion are frequently changed in clinic. Molecular responses in jaw muscles to aberrant dental occlusion are changes are attractive, yet remain are obscure. DESIGN: Unilateral anterior crossbite (UAC) prostheses were applied to Sprague-Dawley rats and then ceased after two weeks to detect the reactions of the masseter, a representative jaw elevator, and the lateral pterygoid muscle (LPM), a representative jaw depressor. RESULTS: Two weeks of UAC elicited mild injury of the two muscles. Myogenesis and protective reactions were detected as increases in αB-crystallin expression in the masseter after 3 days and in the LPM after 2 weeks, and increases in desmin expression in both muscles after 2 weeks. A switch in fibre types from IIb to IIx occurred in the LPM but not in the masseter. Inflammatory responses, shown by the infiltration of inflammatory cells and increases in TNF-α mRNA expression, and fibrosis responses, shown by increased mRNA expression of Type I and III collagens, appeared very mild in the two muscles. These responses were partially recovered by the cessation of UAC. During the whole process, no obvious changes were observed in mitochondrial function, as indicated by the levels of proliferator-activated receptor γ coactivator 1α, mitofusin-2 and voltage-dependent anion channel. CONCLUSIONS: UAC causes injury and very limited inflammatory and fibrosis adaption in the masseter and LPM. Both muscles respond with myogenesis and protective activity. The LPM responds also with muscle fibre isoform alternations. These alterations were partially recovered by the cessation of dental stimulation at an early stage.

2.
Opt Lett ; 44(23): 5768-5771, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774775

RESUMO

Because of random mode coupling, the nonlinear coefficient in few-mode fibers (FMFs) is averaged to an effective value, which can be theoretically modeled and calculated by using the multi-mode Manakov equations. In this Letter, we experimentally measure the effective nonlinear coefficients in a 530-m-long FMF supporting two mode groups, namely, the $ {\rm LP}_{01} $LP01 and $ {\rm LP}_{11} $LP11 mode groups, by exploiting the self-phase and cross-phase modulations of pulsed fields. By using the nonlinear coefficient of the $ {\rm LP}_{01} $LP01 mode as a reference and comparing the spectral broadening of the pulsed fields, we obtain the intra-modal effective nonlinear coefficient of the $ {\rm LP}_{11} $LP11 mode and the inter-modal effective nonlinear coefficient between the $ {\rm LP}_{01} $LP01 and $ {\rm LP}_{11} $LP11 modes. The experimental results are in good agreement with the theoretical predictions of the multi-mode Manakov equations.

3.
J Gastrointest Surg ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31749096

RESUMO

PURPOSE: To establish a novel classification of perigastric arteries by computerized tomography angiography (CTA) and discuss its influence in patients' short-term clinical outcomes. METHODS: The clinical data were analyzed retrospectively from 680 gastric cancer patients. The types of the perigastric artery were classified according to CTA image and we compared the short-term clinical outcomes. RESULTS: The perigastric arteries can be divided into seven categories. Type I, trifurcation of the celiac trunk (CT) (294/343, 85.7%); type II, hepatosplenic trunk, left gastric artery (LGA) arising from the abdominal aorta (8/343, 2.3%); type III, hepatogastric trunk, splenic artery arising from the superior mesenteric artery (SMA) (2/343, 0.6%); type IV, celiacomesenteric trunk (5/343, 1.5%); type V, common hepatic artery (CHA) arising from the SMA, gastrosplenic trunk (11/343, 3.2%); type VI, aberrant (accessory or replaced) left hepatic artery arising from LGA (21/343, 6.1%); and type VII, CHA arising from LGA (2/343, 0.6%). The number of retrieved LNs in the CTA group was significantly higher than that in the non-CTA group. However, the operation time, estimated blood loss, intraoperative vascular injury, and medical cost of the CTA group were significantly less than those in the non-CTA group. Of note, in patients with BMI ≥ 25.0, higher LNs retrieval and less vascular injury were still present in the CTA group, which was of vital importance in clinical practice. Furthermore, the CTA group displayed shorter hospital stay (LOS). CONCLUSION: We established a new perigastric artery classification. Application of the classification can improve the short-term clinical outcomes of patients.

4.
Microbiologyopen ; : e946, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31769202

RESUMO

To assess biofilm formation ability and identify differences in the prevalence of genes involved in biofilm formation among Staphylococcus aureus strains isolated from different food samples, the ability of biofilm formation among 97 S. aureus strains was evaluated using a colorimetric microtiter plate assay. Thirteen genes encoding microbial surface components recognizing adhesive matrix molecules, and the intracellular adhesion genes were detected by PCR using specific primers. Approximately 72% of the isolates produced biofilms. Among these isolates, 54.64% were weak biofilm producers, while 14.43% and 3.09% produced moderate and strong biofilms, respectively. The icaADBC, clfA/B, cidA, and fib genes were detected in all the S. aureus strains, whereas the bap gene was not present in any of the strains. The occurrence of other adhesin genes varied greatly between biofilm-producing and nonbiofilm-producing strains. However, a significant difference was observed between these two groups with respect to the fnbpB, cna, ebps, and sdrC genes. No obvious evidence was found to support the link between PFGE strain typing and the capacity for biofilm formation. Considerable variation in biofilm formation ability was observed among S. aureus strains isolated from food samples. The prevalence of adhesin-encoding genes also varied greatly within strains. This study highlights the importance of biofilm formation and the adhesins of S. aureus strains in food samples.

5.
J Clin Pharm Ther ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730733

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Membranous nephrotic syndrome is one of the most commonly seen paraneoplastic nephropathies. CASE DESCRIPTION: We describe a 59-year-old man who was referred with massive unilateral pleural effusion and was subsequently diagnosed with lung adenocarcinoma. Routine physical and laboratory examinations revealed lower limb oedema, hypoproteinaemia and proteinuria. Examination of a kidney biopsy aspirate confirmed the diagnosis of membranous nephropathy. Aetiological investigations of the kidney pathology ruled out causes other than paraneoplastic nephropathy. Since an epidermal growth factor receptor mutation was identified by analysis of the exfoliated tumour cells in pleural effusion, erlotinib was administered, without further treatment of the membranous nephropathy. Upon control of the patient's lung cancer, the membranous nephropathy completely disappeared, and at the time of this writing, had not recurred over a 4-year follow-up period. WHAT IS NEW AND CONCLUSION: For patients with EGFR-mutation-positive lung adenocarcinoma associated with paraneoplastic membranous nephropathy, erlotinib might serve as a treatment option for both the tumour and the membranous nephropathy.

6.
Adv Exp Med Biol ; 1141: 1-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571163

RESUMO

Absorption, distribution, and excretion of drugs are involved in drug transport across plasma membrane, most of which are mediated by drug transporters. These drug transporters are generally divided into solute carrier (SLC) family and ATP-binding cassette (ABC) family. These transporters not only mediate transport of therapeutic drugs across membrane but also transport various kinds of endogenous compounds. Thus besides being participated in disposal of drug and its clinical efficacy/toxicity, these transporters also play vital roles in maintaining cell homeostasis via regulating transport of endogenous compounds. This chapter will outline classification of drug transporters, their roles in drug disposal/drug response, and remote communication between tissues/organs.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Proteínas Carreadoras de Solutos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Comunicação Celular , Membrana Celular/metabolismo , Humanos , Preparações Farmacêuticas/metabolismo , Proteínas Carreadoras de Solutos/metabolismo
7.
Adv Exp Med Biol ; 1141: 13-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571164

RESUMO

The transport of specific molecules across lipid membranes is an essential function of all living organisms. The processes are usually mediated by specific transporters. One of the largest transporter families is the ATP-binding cassette (ABC) family. More than 40 ABC transporters have been identified in human, which are divided into 7 subfamilies (ABCA to ABCG) based on their gene structure, amino acid sequence, domain organization, and phylogenetic analysis. Of them, at least 11 ABC transporters including P-glycoprotein (P-GP/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) are involved in multidrug resistance (MDR) development. These ABC transporters are expressed in various tissues such as the liver, intestine, kidney, and brain, playing important roles in absorption, distribution, and excretion of drugs. Some ABC transporters are also involved in diverse cellular processes such as maintenance of osmotic homeostasis, antigen processing, cell division, immunity, cholesterol, and lipid trafficking. Several human diseases such as cystic fibrosis, sitosterolemia, Tangier disease, intrahepatic cholestasis, and retinal degeneration are associated with mutations in corresponding transporters. This chapter will describe function and expression of several ABC transporters (such as P-GP, BCRP, and MRPs), their substrates and inhibitors, as well as their clinical significance.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Fenômenos Fisiológicos Celulares , Resistência a Múltiplos Medicamentos/genética , Regulação da Expressão Gênica , Humanos , Filogenia
8.
Adv Exp Med Biol ; 1141: 101-202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571165

RESUMO

Solute carrier (SLC) family transporters utilize an electrochemical potential difference or an ion gradient generated by primary active transporters for transporting their substrates across biological membranes. These transporters are categorized as facilitated transporters or secondary active transporters. More than 300 SLC transporters have been identified. SLC transporters related to drug transport mainly include SLC21 gene subfamily (organic anion-transporting polypeptides, OATPs), SLC22A gene subfamily (organic anion transporters, OATs; organic cation transporters, OCTs; or organic cation/carnitine transporters, OCTNs), SLC15A gene subfamily (peptide transporters, PEPTs), and SLC47A gene subfamily (multidrug and toxin extrusion, MATEs). In general, OCTs transport organic cations, OATPs transport large and fairly hydrophobic organic anions, OATs transport the smaller and more hydrophilic organic anions, and PEPTs are responsible for the uptake of di-/tripeptides and peptide-like drugs. MATEs are responsible for efflux of organic cations. These transporters also transport some endogenous substances, indicating that the dysfunction of SLCs not only disrupts homeostasis but also largely impacts on the disposition of their substrate drugs. This chapter will discuss these SLC family transporters, with an emphasis on tissue distribution, substrate specificity, transporter physiology, and clinical significance.


Assuntos
Proteínas Carreadoras de Solutos , Animais , Cátions/metabolismo , Humanos , Peptídeos/metabolismo , Preparações Farmacêuticas/metabolismo , Proteínas Carreadoras de Solutos/metabolismo , Especificidade por Substrato , Distribuição Tecidual/fisiologia
9.
Adv Exp Med Biol ; 1141: 241-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571167

RESUMO

Drug transporters are considered to be determinants of drug disposition and effects/toxicities by affecting the absorption, distribution, and excretion of drugs. Drug transporters are generally divided into solute carrier (SLC) family and ATP binding cassette (ABC) family. Widely studied ABC family transporters include P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance proteins (MRPs). SLC family transporters related to drug transport mainly include organic anion-transporting polypeptides (OATPs), organic anion transporters (OATs), organic cation transporters (OCTs), organic cation/carnitine transporters (OCTNs), peptide transporters (PEPTs), and multidrug/toxin extrusions (MATEs). These transporters are often expressed in tissues related to drug disposition, such as the small intestine, liver, and kidney, implicating intestinal absorption of drugs, uptake of drugs into hepatocytes, and renal/bile excretion of drugs. Most of therapeutic drugs are their substrates or inhibitors. When they are comedicated, serious drug-drug interactions (DDIs) may occur due to alterations in intestinal absorption, hepatic uptake, or renal/bile secretion of drugs, leading to enhancement of their activities or toxicities or therapeutic failure. This chapter will illustrate transporter-mediated DDIs (including food drug interaction) in human and their clinical significances.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Interações de Medicamentos , Preparações Farmacêuticas , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transporte Biológico , Interações Alimento-Droga , Humanos , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos , Preparações Farmacêuticas/metabolismo
10.
Adv Exp Med Biol ; 1141: 407-466, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571171

RESUMO

Blood-brain interfaces comprise the cerebral microvessel endothelium forming the blood-brain barrier (BBB) and the epithelium of the choroid plexuses forming the blood-cerebrospinal fluid barrier (BCSFB). Their main functions are to impede free diffusion between brain fluids and blood; to provide transport processes for essential nutrients, ions, and metabolic waste products; and to regulate the homeostasis of central nervous system (CNS), all of which are attributed to absent fenestrations, high expression of tight junction proteins at cell-cell contacts, and expression of multiple transporters, receptors, and enzymes. Existence of BBB is an important reason that systemic drug administration is not suitable for the treatment of CNS diseases. Some diseases, such epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and diabetes, alter BBB function via affecting tight junction proteins or altering expression and function of these transporters. This chapter will illustrate function of BBB, expression of transporters, as well as their alterations under disease status.


Assuntos
Barreira Hematoencefálica , Proteínas de Membrana Transportadoras , Preparações Farmacêuticas , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo
11.
Adv Exp Med Biol ; 1141: 467-504, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571172

RESUMO

Blood-retinal barrier (BRB) includes inner BRB (iBRB) and outer BRB (oBRB), which are formed by retinal capillary endothelial (RCEC) cells and by retinal pigment epithelial (RPE) cells in collaboration with Bruch's membrane and the choriocapillaris, respectively. Functions of the BRB are to regulate fluids and molecular movement between the ocular vascular beds and retinal tissues and to prevent leakage of macromolecules and other potentially harmful agents into the retina, keeping the microenvironment of the retina and retinal neurons. These functions are mainly attributed to absent fenestrations of RCECs, tight junctions, expression of a great diversity of transporters, and coverage of pericytes and glial cells. BRB existence also becomes a reason that systemic administration for some drugs is not suitable for the treatment of retinal diseases. Some diseases (such as diabetes and ischemia-reperfusion) impair BRB function via altering tight junctions, RCEC death, and transporter expression. This chapter will illustrate function of BRB, expressions and functions of these transporters, and their clinical significances.


Assuntos
Barreira Hematorretiniana , Proteínas de Membrana Transportadoras , Expressão Gênica , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Retina/metabolismo , Doenças Retinianas/fisiopatologia , Junções Íntimas
12.
Adv Exp Med Biol ; 1141: 505-548, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571173

RESUMO

The placenta is the only organ linking two different individuals, mother and fetus, termed as blood-placental barrier. The functions of the blood-placental barrier are to regulate material transfer between the maternal and fetal circulation. The main functional units are the chorionic villi within which fetal blood is separated by only three or four cell layers (placental membrane) from maternal blood in the surrounding intervillous space. A series of drug transporters such as P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), multidrug resistance-associated proteins (MRP1, MRP2, MRP3, MRP4, and MRP5), organic anion-transporting polypeptides (OATP4A1, OATP1A2, OATP1B3, and OATP3A1), organic anion transporter 4 (OAT4), organic cation transporter 3 (OCT3), organic cation/carnitine transporters (OCTN1 and OCTN2), multidrug and toxin extrusion 1 (MATE1), and equilibrative nucleoside transporters (ENT1 and ENT2) have been demonstrated on the apical membrane of syncytiotrophoblast, some of which also expressed on the basolateral membrane of syncytiotrophoblast or fetal capillary endothelium. These transporters are involved in transport of most drugs in the placenta, in turn, affecting drug distribution in fetus. Moreover, expressions of these transporters in the placenta often vary along with the gestational ages and are also affected by pathophysiological factor. This chapter will mainly illustrate function and expression of these transporters in placentas, their contribution to drug distribution in fetus, and their clinical significance.


Assuntos
Regulação da Expressão Gênica , Proteínas de Membrana Transportadoras , Placenta , Feminino , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Placenta/metabolismo , Gravidez , Distribuição Tecidual , Trofoblastos/metabolismo
13.
Nanoscale ; 11(39): 18009-18014, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31570912

RESUMO

All-inorganic perovskite (CsPbX3) quantum dots (QDs) have achieved unprecedented success in various applications due to their outstanding performance. Nevertheless, the inherent instability of these QDs severely limits their practical applications. Here, ultra-stable full visible spectrum CsPbX3 (X = Cl, Br, I) QD glasses are prepared successfully. For the first time, the full spectrum tunable up-conversion (UC) emission of CsPbX3 QD glasses ranging from 420 nm to 711 nm under excitation with an 800 nm femtosecond (fs) laser was achieved. Importantly, the two-photon absorption properties, the exciton binding energy and the UC full width at half maximum (FWHM) of CsPbCl1.5Br1.5 (blue), CsPbBr3 (green), and CsPbBr1.5I1.5 (red) QD glasses were studied in depth. Furthermore, CsPbCl1.5Br1.5 showed the highest exciton binding energy (∼87.5 meV), allowing the CsPbCl1.5Br1.5 QD glass to act as a good optical gain material that could more easily achieve amplified spontaneous emission (ASE).

14.
Phys Chem Chem Phys ; 21(39): 21806-21813, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31573002

RESUMO

Due to the intrinsic heterogeneity of nanocatalysis, many underlying catalytic details on nanocatalysts are hidden in ensemble-averaged measurements. Here, the single-molecule approach was adopted to study the temperature-dependent catalytic kinetics and dynamics of individual Pt nanoparticles and then reveal the thermodynamics of individual catalytic steps on Pt nanoparticles. In this way, the temperature-dependent catalytic kinetics (the effective rate constant of the product formation process, the rate constants of the direct/indirect production desorption process and the substrate adsorption equilibrium constants) and thermodynamics (free energy, entropy and enthalpy of substrate adsorption) were obtained systematically at the single particle level. Based on such results, we further obtained the activation energies of the catalytic product formation step and the direct/indirect product desorption steps. Moreover, by analyzing the temperature-dependent surface restructuring rates of individual Pt nanocatalysts, the activation energies of both the catalysis-induced surface restructuring and the spontaneous surface restructuring were obtained for the first time. All these results obtained here deepen our understanding of the catalytic thermodynamics of nanocatalysts.

15.
J Cell Biochem ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478229

RESUMO

Vascular endothelial growth factor C (VEGF-C) has been reported to be responsible for the lymphatic vessel density, tumor staging and lymph node metastasis, resulting in the failure of nasopharyngeal carcinoma (NPC) after radiotherapy. Therefore, the aim of this study was to explore the effects and the underlying mechanism of VEGF-C on the radiotherapy and in the human NPC cell lines CNE-2. In our study, VEGF-C silenced CNE-2 cells were stably established. Different small interfering VEGF-C (si-VEGFC) were transfected into CNE-2 cells and combined with 8 Gy X-ray. The proliferation, cloning ability, DNA damage, and apoptosis of CNE-2 cells were evaluated by counting kit-8 (CCK-8), colony-forming assay, comet assays, and flow cytometry, respectively. Moreover, the VEGFC knockdown involved signaling pathways in CNE-2 cells were predicted by polymerase chain reaction (PCR) array, and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Results demonstrated that silencing VEGF-C combined with radiation can significantly inhibit the proliferation and cloning ability, while increase the apoptosis and DNA damage of CNE-2 cells, thereby promote the radiosensitivity. Furthermore, the effects of silencing VEGF-C probably through activating the NF-kB signal pathway. In conclusion, the study demonstrated that VEGF-C may be a potential target to increase the radiosensitivity in NPC by activating NF-kB signaling.

16.
Appl Opt ; 58(19): 5301-5309, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503629

RESUMO

The optical behavior of twisted nematic liquid crystals (TNLCs) is revealed through an angular scanning technique. Experimental results show that the optical rotation and degree of polarization of transmitted light are dependent on the polarization direction of incident light. The optical rotation is reciprocal, i.e., the polarization direction of incident and transmitted light can reciprocate when optical rotation is π/2. In some cases, the optical rotation is zero. The orientation of alignment layers in the TN cell can be determined from the behavior of optical rotation, which agrees with the measurement by an atomic force microscope. The experimental results are explained with the model of circularly polarized light based on the circular birefringence effect. Linearly polarized incident light is the superposition of right- and left-handed circularly polarized light. The propagation velocity of circularly polarized light in the LC is relevant to the polarization direction of incident light, so that the refractive indices of left- and right-handed circularly polarized light, n- and n+, or circular birefringence Δn(=n--n+) are not constants. As a result, when a linearly polarized light with the wavelength λ propagates through a TN cell with the cell gap l, the polarization direction of transmitted light is rotated to an angle Δθ. The optical rotation Δθ(=π(n--n+)l/λ) is dependent on the polarization direction of incident light, whereas the averaged refractive index ⟨n⟩(=(n-+n+)/2) can be independent of that. The incident light is partially linearly polarized light in our experiments, so that the degree of polarization of transmitted light varies with the polarization direction of incident light because the optical rotatory rates for the primary and secondary light beams are different.

17.
J Bone Miner Res ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498905

RESUMO

Calcium and its putative receptor (CaSR) control skeletal development by pacing chondrocyte differentiation and mediating osteoblast (OB) function during endochondral bone formation-an essential process recapitulated during fracture repair. Here, we delineated the role of the CaSR in mediating transition of callus chondrocytes into the OB lineage and subsequent bone formation at fracture sites and explored targeting CaSRs pharmacologically to enhance fracture repair. In chondrocytes cultured from soft calluses at a closed, unfixed fracture site, extracellular [Ca2+ ] and the allosteric CaSR agonist (NPS-R568) promoted terminal differentiation of resident cells and the attainment of an osteoblastic phenotype. Knockout (KO) of the Casr gene in chondrocytes lengthened the chondrogenic phase of fracture repair by increasing cell proliferation in soft calluses but retarded subsequent osteogenic activity in hard calluses. Tracing growth plate (GP) and callus chondrocytes that express Rosa26-tdTomato showed reduced chondrocyte transition into OBs (by >80%) in the spongiosa of the metaphysis and in hard calluses. In addition, KO of the Casr gene specifically in mature OBs suppressed osteogenic activity and mineralizing function in bony calluses. Importantly, in experiments using PTH (1-34) to enhance fracture healing, co-injection of NPS-R568 not only normalized the hypercalcemic side effects of intermittent PTH (1-34) treatment in mice but also produced synergistic osteoanabolic effects in calluses. These data indicate a functional role of CaSR in mediating chondrogenesis and osteogenesis in the fracture callus and the potential of CaSR agonism to facilitate fracture repair. © 2019 American Society for Bone and Mineral Research.

18.
Free Radic Biol Med ; 143: 454-470, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31472247

RESUMO

Brachial plexus avulsion (BPA) occurs when the spinal nerve roots are pulled away from the surface of the spinal cord and disconnects neuronal cell body from its distal downstream axon, which induces massive motoneuron death, motor axon degeneration and de-innervation of targeted muscles, thereby resulting in permanent paralysis of motor functions in the upper limb. Avulsion injury triggers oxidative stress and intense local neuroinflammation at the lesioned site, leading to the death of most motoneurons. Berberine (BBR), a natural isoquinoline alkaloid derived from medicinal herbs of Berberis and Coptis species, has been reported to possess neuro-protective, anti-inflammatory and anti-oxidative effects in various animal models of central nervous system (CNS)-related disorders. In this study, we aimed to investigate the effect of BBR on motoneuron survival and axonal regeneration following spinal root avulsion plus re-implantation in rats. Our results indicated BBR significantly accelerated motor function recovery in the forelimb as revealed by the increased Terzis grooming test score, facilitated motor axon regeneration as evidenced by the elevated number of Fluoro-Gold-labeled and P75-positive regenerative motoneurons. The survival of motoneurons was notably promoted by BBR administration presented with boosted ChAT-immunopositive and neutral red-stained neurons. BBR treatment efficiently alleviated muscle atrophy, attenuated functional motor endplates loss in biceps and prevented the reduction of motor axons in the musculocutaneous nerve. Additionally, BBR treatment markedly mitigated the avulsion-induced neuroinflammation via inhibiting microglial and astroglial reactivity, up-regulated the expression of antioxidative indicator Cu/Zn SOD, and down-regulated the levels of nNOS, 3-NT, lipid peroxidation and NF-κB, as well as promoted SIRT1, PI3K and Akt activation. Collectively, BBR might be a promising therapy to assist re-implantation surgery for the treatment of BPA.

19.
J Phys Chem Lett ; 10(18): 5402-5407, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31460765

RESUMO

Understanding the heterogeneous electron-transfer (ET) kinetics on graphene is essential for its extensive applications. Here, on the basis of the redox-induced fluorescence variation of monolayer graphene itself, the heterogeneous ET kinetics at the interface between the electrode and the monolayer graphene was studied label-freely at the single-sheet level. By tuning the defect density on graphene, an optimal heterogeneous ET rate was observed at a moderate defect density, indicating defect-driven ET kinetics. The heterogeneities of both the intrasheet and intersheet ET kinetics were revealed at the single-sheet level. With the optimal defective graphene sheets as a sensing material for oxygen gas, a cost-effective electrochemical oxygen sensor was obtained with high sensitivity, fast response/recovery, and remarkable durability. The results obtained here deepen our understanding of the electrochemical properties of graphene and imply that rational defect control can enhance the ET process between the electrode and graphene and then improve the performance of graphene-based functional materials or devices.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1040-1045, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418354

RESUMO

OBJECTIVE: To study the long-term efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of relapsed patients with B-cell acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 7 patients with B-cell ALL relapsed after allo-HSCT were treated with CD19 CAR-T cells from September 2015 to March 2018. Among them, 6 had hematological recurrence and 1 had positive of MRD. They all were treated with a single infusion of CAR-T cells. FC chemotherapy regimen was administered before transfusion. The median number of CAR-T cells transfused was 6.0 (range 4.0-8.6) )×106/kg. Long-term efficacy and toxicity were evaluated. RESULTS: Bone marrow examination performed at d 30 after CAR-T infusion showed that all 7 patients achieved complete remission and MRD negative, grade I CRS for 1 case and grade II CRS for 6 cases, two of them had mild neurotoxicity, which was controlled by treatment. Two patients presented grade VI intestinal GVHD after CAR-T infusion. The median follow-up time was 18 months (range 12-42). Follow-up showed that two patients relapsed at 9 months and 14 months after treatment, out of 2 patients one died of progressive disease and the other reachived the hematological remission, but MRD was positive after CD22 CAR-T cell therapy. At present, five patients are disease-free survival, moreover showed complete donor chimerism. One year after CAR-T cell therapy, the results of immune reconstitution showed that CD4 level was more than 300×106/L in 5 patients who disease-free survived. Among them, 3 patients had poor recovery of immunoglobulin and received gamma globulin replacement therapy. CONCLUSION: All patients are followed up for at least one year. The preliminary efficacy and safety are satisfactory. CAR-T cell infusion is an effective method for the treatment of B-ALL recurrence after allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfócitos B , Humanos , Receptores de Antígenos Quiméricos , Linfócitos T
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