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1.
Proc Natl Acad Sci U S A ; 120(29): e2207993120, 2023 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-37428931

RESUMEN

Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 (NOS2) expression and downregulated mitochondria function-associated genes. NOS inhibition partially restored the expression of these genes, and rescued mitochondrial function and ATP production. Correspondingly, Nos2-/- mice were protected from age-related OA development. Taken together, the TLR2-NOS axis promotes human chondrocyte dysfunction and murine OA development, and targeted interventions may provide therapeutic and preventive approaches in OA.


Asunto(s)
Cartílago Articular , Osteoartritis , Humanos , Ratones , Animales , Condrocitos/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Osteoartritis/metabolismo , Receptores Toll-Like/metabolismo , Cartílago Articular/metabolismo , Células Cultivadas
2.
Small ; : e2311648, 2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38402429

RESUMEN

Ternary strategy with integration characteristics and adaptability is a simple and effective method for blooming of the performance of photovoltaic devices. Herein, a novel wideband gap polymer donor PBB2-Hs is synthesized as the guest component to optimize all-polymer solar cells (all-PSCs). High-energy photon absorption and long exciton lifetime of PBB2-Hs constitute efficient energy transfer. Good miscibility and cascade energy levels promote the formation of alloy-like structure between PBB2-Hs and host system. The dual working mechanisms greatly improve photon capture and charge transfer in active layers. Additionally, the introduction of PBB2-Hs also optimizes the ordered molecular stacking of acceptors and suppresses molecular peristalsis. Upon adding 15 wt% PBB2-Hs, the ternary all-PSC achieved a champion efficiency of 17.66%, and can still maintain 82% photostability (24 h) and 91% storage stability (1000 h) of the original PCE. Moreover, the strong molecular stacking and entanglement between PBB2-Hs and the host material increased the elongation at break of ternary blend film by 1.6 times (16.2%), allowing the flexible device to maintain 83% of the original efficiency after 800 bends (R = 5 mm). This work highlights the effectiveness of guest polymer on simultaneously improving photovoltaic performance, photostability and mechanical stability in all-PSCs.

3.
Mol Biol Rep ; 51(1): 680, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796595

RESUMEN

Menstrual blood-derived endometrial stem cells (MenSCs) have attracted increasing interest due to their excellent safety, and lack of ethical dilemma as well as their ability to be periodically obtained in a noninvasive manner. However, although preclinical research as shown the therapeutic potential of MenSCs in several diseases, their poor cell survival and low engraftment at disease sites reduce their clinical efficacy. Flotillins (including Flot1 and Flot2) are implicated in various cellular processes, such as vesicular trafficking, signal transduction, cell proliferation, migration and apoptosis. In this study, we aimed to determine the effects of Flotillins on MenSCs survival, proliferation and migration. Our experimental results show that MenSCs were modified to overexpress Flot1 and/or Flot2 without altering their intrinsic characteristics. Flot1 and Flot2 co-overexpression promoted MenSC viability and proliferation capacity. Moreover, Flot1 or Flot2 overexpression significantly promoted the migration and inhibited the apoptosis of MenSCs compared with the negative control group, and these effects were stronger in the Flot1 and Flot2 gene co-overexpression group. However, these effects were significantly reversed after Flot1 and/or Flot2 knockdown. In conclusion, our results indicate that Flot1 and Flot2 overexpression in MenSCs improved their proliferation and migration and inhibited their apoptosis, and this might be an effective approach to improve the efficiency of cell-based therapies.


Asunto(s)
Apoptosis , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Proteínas de la Membrana , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Femenino , Endometrio/citología , Endometrio/metabolismo , Células Madre/metabolismo , Células Madre/citología , Células Cultivadas , Transducción de Señal
4.
Histochem Cell Biol ; 160(1): 11-25, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37014442

RESUMEN

Experimental autoimmune encephalomyelitis (EAE) is a classical animal model of human multiple sclerosis (MS) that is most commonly used to study the neuropathology and therapeutic effects of the disease. Telocytes (TCs) are a specialized type of interstitial or mesenchymal cell first identified by Popescu in various tissues and organs. However, the existence, distribution and role of CD34+ stromal cells (SCs)/TCs in the EAE-induced mouse spleen remain to be elucidated. We conducted immunohistochemistry, immunofluorescence (double staining for CD34 and c-kit, vimentin, F4/80, CD163, Nanog, Sca-1, CD31 or tryptase) and transmission electron microscopy experiments to investigate the existence, distribution and role of CD34+ SCs/TCs in the EAE-induced mouse spleen. Interestingly, immunohistochemistry, double-immunofluorescence, and transmission electron microscopy results revealed that CD34+ SCs/TCs were significantly upregulated in the EAE mouse spleen. Immunohistochemical or double-immunofluorescence staining of CD34+ SCs/TCs showed positive expression for CD34, c-kit, vimentin, CD34/vimentin, c-kit/vimentin and CD34/c-kit, and negative expression for CD31 and tryptase. Transmission electron microscopy (TEM) results demonstrated that CD34+ SCs/TCs established close connections with lymphocytes, reticular cells, macrophages, endothelial cells and erythrocytes. Furthermore, we also found that M1 (F4/80) or M2 (CD163) macrophages, and haematopoietic, pluripotent stem cells were markedly increased in EAE mice. Our results suggest that CD34+ SCs/TCs are abundant and may play a contributing role in modulating the immune response, recruiting macrophages and proliferation of haematopoietic and pluripotent stem cells following injury to promote tissue repair and regeneration in EAE mouse spleens. This suggests that their transplantation combined with stem cells might represent a promising therapeutic target for the treatment and prevention of multiple autoimmune and chronic inflammatory disorders.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Células Madre Pluripotentes , Telocitos , Animales , Ratones , Antígenos CD34/metabolismo , Moléculas de Adhesión Celular/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Células Endoteliales/metabolismo , Células Madre Pluripotentes/metabolismo , Bazo , Células del Estroma/metabolismo , Telocitos/metabolismo , Telocitos/patología , Triptasas/metabolismo , Vimentina/metabolismo
5.
J Med Virol ; 95(2): e28492, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36633204

RESUMEN

Mammalian orthoreovirus (MRV) infects many mammalian species including humans, bats, and domestic animals. To determine the prevalence of MRV in bats in the United States, we screened more than 900 bats of different species collected during 2015-2019 by a real-time reverse-transcription polymerase chain reaction assay; 4.4% bats tested MRV-positive and 13 MRVs were isolated. Sequence and phylogenetic analysis revealed that these isolates belonged to four different strains/genotypes of viruses in Serotypes 1 or 2, which contain genes similar to those of MRVs detected in humans, bats, bovine, and deer. Further characterization showed that these four MRV strains replicated efficiently on human, canine, monkey, ferret, and swine cell lines. The 40/Bat/USA/2018 strain belonging to the Serotype 1 demonstrated the ability to infect and transmit in pigs without prior adaptation. Taken together, this is evidence for different genotypes and serotypes of MRVs circulating in US bats, which can be a mixing vessel of MRVs that may spread to other species, including humans, resulting in cross-species infections.


Asunto(s)
Quirópteros , Ciervos , Orthoreovirus de los Mamíferos , Orthoreovirus , Animales , Perros , Humanos , Bovinos , Estados Unidos , Porcinos , Orthoreovirus de los Mamíferos/genética , Filogenia , Hurones
6.
Sensors (Basel) ; 23(3)2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36772369

RESUMEN

With the development of 5G, artificial intelligence, and the Internet of Things, diversified sensors (such as the signal acquisition module) have become more and more important in people's daily life. According to the extensive use of various distributed wireless sensors, powering them has become a big problem. Among all the powering methods, the self-powered sensor system based on triboelectric nanogenerators (TENGs) has shown its superiority. This review focuses on four major application areas of wireless sensors based on TENG, including environmental monitoring, human monitoring, industrial production, and daily life. The perspectives and outlook of the future development of self-powered wireless sensors are discussed.

7.
Macromol Rapid Commun ; 42(10): e2000757, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33870582

RESUMEN

With the significant progress of low bandgap non-fullerene acceptors, the development of wide bandgap (WBG) donors possessing ideal complementary absorption is of crucial importance to further enhance the photovoltaic performance of organic solar cells. An ideal strategy to design WBG donors is to down-shift the highest occupied molecular orbital (HOMO) and up-shift the lowest unoccupied molecular orbital (LUMO). A properly low-lying HOMO of the donor is favorable to obtaining a high open-circuit voltage, and a properly high-lying LUMO of the donor is conductive to efficient exciton dissociation. This work provides a new strategy to enlarge the bandgap of a polymer with simultaneously decreased HOMO and increased LUMO by increasing the polymer backbone curvature. The polymer PIDT-fDTBT with a large molecular backbone curvature shows a decreased HOMO of -5.38 eV and a prominently increased LUMO of -3.35 eV relative to the linear polymer PIDT-DTBT (EHOMO = -5.30 eV, ELUMO = -3.55 eV). The optical bandgap of PIDT-fDTBT is obviously broadened from 1.75 to 2.03 eV. This work demonstrates that increasing the polymer backbone curvature can effectively broaden the bandgap by simultaneously decreasing HOMO and increasing LUMO, which may guide the design of WBG conjugated materials.


Asunto(s)
Energía Solar , Conductividad Eléctrica , Polímeros
8.
Macromol Rapid Commun ; 39(8): e1700782, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29436043

RESUMEN

Benzo[c][1,2,5]oxadiazole (BO) moiety is a strong electron-withdrawing unit compared to benzo[c][1,2,5]thiadiazole (BT). It is usually introduced as an acceptor to construct narrow band-gap donor-acceptor (D-A) materials. Herein, the π-extended conjugated moiety dithieno[3',2':3,4″;2,3″:5,6]benzo[1,2-c][1,2,5]oxadiazole (BOT) was adopted as the acceptor moiety to design D-A polymers. Considering the more extended π-conjugated molecular system of BOT compared to the BO unit, a narrower optical band-gap is expected for BOT-based IDT polymer (PIDT-BOT). Unexpectedly, the UV-vis absorption spectra of PIDT-BOT films display a great hypochromatic shift of about 60 nm compared to a BO-based analog (PIDT-BO). The optical band-gaps of the materials are broadened from 1.63 eV (PIDT-BO) to 2.00 eV (PIDT-BOT) accordingly. Although the range of external quantum efficiency (EQE) of PIDT-BOT-based polymer solar cell (PSC) devices is not as wide as for PIDT-BO-based devices, the EQE response intensities of the PIDT-BOT based device are evidently high. As a result, PSC devices based on PIDT-BOT reveal the best power conversion efficiency at 6.08%.


Asunto(s)
Oxadiazoles/química , Polímeros/química , Tiofenos/química , Energía Solar
9.
Macromol Rapid Commun ; 39(21): e1800446, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30144192

RESUMEN

The 2D asymmetric benzodithiophene (BDT) unit is used as a donor unit to construct one new polymer PBDTBDD-Th with benzo[1,2-c:4,5-c']dithiophene-4,8-dione (BDD) as acceptor building block. In comparison to the polymer PBDTsTh-BDD with a side chain containing a sulfur atom, the devices based on PBDTBDD-Th/ITIC show better performance due to the introduction of carbon atoms in the side chain, which could weaken the self-aggregations of polymer chains. As a result, the devices based on PBDTBDD-Th/ITIC blends yield power conversion efficiencies (PCEs) over 10%, much higher than those based on PBDTsTh-BDD/ITIC blends (7.09%). The exciton dissociation probabilities (P diss ) of a device based on PBDTBDD-Th/ITIC blends is 95.3%, which suggests that the device achieves good exciton dissociation and charge transfer. In general, the polymer PBDTBDD-Th shows capability to increase the PCEs of polymer solar cells (PSCs) with a non-fullerene acceptor.


Asunto(s)
Polímeros/química , Energía Solar , Tiofenos/química , Estructura Molecular , Polímeros/síntesis química
10.
Appl Microbiol Biotechnol ; 102(20): 8979-8987, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30056515

RESUMEN

A low-cost floating photobioreactor (PBR) without the use of aeration and/or an agitation device, in which carbon was supplied in the form of bicarbonate and only wave energy was utilized for mixing, was developed in our previous study. Scaling up is a common challenge in the practical application of PBRs and has not yet been demonstrated for this new design. To fill this gap, cultivation of Spirulina platensis was conducted in this study. The results demonstrated that S. platensis had the highest productivity at 0.3 mol L-1 sodium bicarbonate, but the highest carbon utilization (104 ± 2.6%) was obtained at 0.1 mol L-1. Culture of Spirulina aerated with pure oxygen resulted in only minor inhibition of growth, indicating that its productivity will not be significantly reduced even if dissolved oxygen is accumulated to a high level due to intermittent mixing resulting from the use of wave energy. In cultivation using a floating horizontal photobioreactor at the 1.0 m2 scale, the highest biomass concentration of 2.24 ± 0.05 g L-1 was obtained with a culture depth of 5.0 cm and the highest biomass productivity of 18.9 g m-2 day-1 was obtained with a depth of 10.0 cm. This PBR was scaled up to 10 m2 (1000 L) with few challenges; biomass concentration and productivity during ocean testing were little different than those at the 1.0 m2 (100 L) scale. However, the larger PBR had an apparent carbon utilization efficiency of 45.0 ± 2.8%, significantly higher than the 39.4 ± 0.9% obtained at the 1 m2 scale. These results verified the ease of scaling up floating horizontal photobioreactors and showed their great potential in commercial applications.


Asunto(s)
Oxígeno/metabolismo , Spirulina/crecimiento & desarrollo , Biomasa , Microalgas/crecimiento & desarrollo , Microalgas/metabolismo , Oxígeno/análisis , Fotobiorreactores , Spirulina/metabolismo
11.
J Gen Virol ; 98(4): 577-584, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28100299

RESUMEN

In our previous studies, the reassortant virus containing only the PR8 H1N1 matrix (M) gene in the background of the modified bat influenza Bat09 : mH1mN1 virus could be generated. However, whether M genes from other origins can be rescued in the background of the Bat09 : mH1mN1 virus and whether the resulting novel reassortant virus is virulent remain unknown. Herein, two reassortant viruses were generated in the background of the Bat09 : mH1mN1 virus containing either a North American or a Eurasian swine influenza virus M gene. These two reassortant viruses and the reassortant virus with PR8 M as well as the control Bat09 : mH1mN1 virus replicated efficiently in cultured cells, while the reassortant virus with PR8 M grew to a higher titre than the other three viruses in tested cells. Mouse studies showed that reassortant viruses with either North American or Eurasian swine influenza virus M gene did not enhance virulence, whereas the reassortant virus with PR8 M gene displayed higher pathogenicity when compared to the Bat09 : mH1mN1 virus. This is most likely due to the fact that the PR8 H1N1 virus is a mouse-adapted virus. Furthermore, reassortment potential between the Bat09 : mH1mN1 virus and an H3N2 swine influenza virus (A/swine/Texas/4199-2/1998) was investigated using co-infection of Madin-Darby canine kidney cells, but no reassortant viruses were detected. Taken together, our results indicate that the modified bat influenza virus is most likely incapable of reassortment with influenza A viruses with in vitro co-infection experiments, although reassortant viruses with different M genes can be generated by reverse genetics.


Asunto(s)
Variación Genética , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Infecciones por Orthomyxoviridae/veterinaria , Virus Reordenados/genética , Virus Reordenados/aislamiento & purificación , Proteínas de la Matriz Viral/genética , Animales , Quirópteros , Modelos Animales de Enfermedad , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Ratones , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/virología , Porcinos , Carga Viral , Virulencia , Replicación Viral
12.
J Gen Virol ; 98(1): 31-42, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28008819

RESUMEN

Although several studies have exploited the effects of PB1-F2 in swine influenza viruses, its contribution to the pathogenicity of swine influenza viruses remains unclear. Herein, we investigated the effects of PB1-F2 on the pathogenicity of influenza virus using a virulent H1N1 A/swine/Kansas/77778/2007 (KS07) virus, which expresses a full-length PB1-F2, in mice and pigs. Using reverse genetics, we generated the wild-type KS07 (KS07_WT), a PB1-F2 knockout mutant (KS07_K/O) and its N66S variant (KS07_N66S). KS07_K/O showed similar pathogenicity in mice to the KS07_WT, whereas KS07_N66S displayed enhanced virulence when compared to the other two viruses. KS07_WT exhibited more efficient replication in lungs and nasal shedding in infected pigs than the other two viruses. Pigs infected with the KS07_WT had higher pulmonary levels of granulocyte-macrophage colony-stimulating factor, IFN-γ, IL-6 and IL-8 at 3 and 5 days post-infection, as well as lower levels of IL-2, IL-4 and IL-12 at 1 day post-infection compared to those infected with the KS07_K/O. These results indicate that PB1-F2 modulates KS07 H1N1 virus replication, pathogenicity and innate immune responses in pigs and the single substitution at position 66 (N/S) in the PB1-F2 plays a critical role in virulence in mice. Taken together, our results provide new insights into the effects of PB1-F2 on the virulence of influenza virus in swine and support PB1-F2 as a virulence factor of influenza A virus in a strain- and host-dependent manner.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Infecciones por Orthomyxoviridae/veterinaria , Proteínas Virales/genética , Animales , Línea Celular , Femenino , Técnicas de Inactivación de Genes , Células HEK293 , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/virología , Porcinos/inmunología , Porcinos/virología , Enfermedades de los Porcinos/virología , Virulencia/genética , Factores de Virulencia/genética , Replicación Viral/genética
13.
Cell Immunol ; 295(1): 36-45, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25734547

RESUMEN

UNLABELLED: Few studies have investigated the impact of liver cirrhosis on dendritic cell function. The purpose of this study was to compare the activation and antigen-presentation capacity of monocyte-derived dendritic cells (MoDC) from cirrhotic patients (CIR) relative to healthy donors (HD). MoDC from CIR and HD were matured, phenotyped, irradiated and pulsed with 15mer peptides for two hepatocellular carcinoma-related antigens, alphafetoprotein and glypican-3, then co-cultured with autologous T-cells. Expanded T-cells were evaluated by interferon-gamma ELISPOT and intracellular staining. 15 CIR and 7 HD were studied. While CD14+ monocytes from CIR displayed enhanced M2 polarization, under MoDC-polarizing conditions, we identified no significant difference between HD and CIR in maturation-induced upregulation of co-stimulation markers. Furthermore, no significant differences were observed between CIR and HD in subsequent expansion of tumor antigen-specific IFNγ+ T-cells. CONCLUSION: MoDCs isolated from cirrhotic individuals retain similar capacity for in vitro activation, maturation and antigen-presentation as those from healthy donors.


Asunto(s)
Presentación de Antígeno/inmunología , Diferenciación Celular/inmunología , Células Dendríticas/inmunología , Cirrosis Hepática/inmunología , Monocitos/inmunología , Adulto , Anciano , Proliferación Celular , Células Cultivadas , Técnicas de Cocultivo , Células Dendríticas/metabolismo , Ensayo de Immunospot Ligado a Enzimas , Citometría de Flujo , Voluntarios Sanos , Humanos , Inmunofenotipificación , Interferón gamma/inmunología , Interferón gamma/metabolismo , Receptores de Lipopolisacáridos/inmunología , Receptores de Lipopolisacáridos/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Macrófagos/clasificación , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo
14.
Cell Immunol ; 297(2): 87-93, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26205091

RESUMEN

The difference in immunoregulatory effects between sirolimus and tacrolimus on kidney transplantation remains unclear. In this study, a total of 18 living-donor-related kidney transplant recipients received sirolimus (n=8) or tacrolimus (n=10) treatment. Kidney function, acute rejection, peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs), CD19(+)CD5(+)CD1d(+) regulatory B cells (Bregs), and panel reactivity antibody were analyzed after one and three years. Th1/2 cell polarization was also determined at one year. The proportion of Tregs in the recipients receiving tacrolimus significantly decreased to 3.69% and 2.49% at one and three years, respectively, compared to 6.59% in controls, whereas the proportion in the recipients receiving sirolimus remained at 6.67% and 5.66%, respectively. However, no differences in kidney function, acute rejection, proportion of Bregs, panel reactivity antibody, or the frequencies of Th1/2 cells were identified. In conclusion, unlike tacrolimus, sirolimus maintains the proportion of Tregs in kidney transplant recipients.


Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Aloinjertos , Linfocitos B Reguladores/efectos de los fármacos , Linfocitos B Reguladores/inmunología , Recuento de Linfocito CD4 , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Factores de Tiempo
15.
Angew Chem Int Ed Engl ; 54(46): 13586-9, 2015 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-26403214

RESUMEN

We studied charge transport through core-substituted naphthalenediimide (NDI) single-molecule junctions using the electrochemical STM-based break-junction technique in combination with DFT calculations. Conductance switching among three well-defined states was demonstrated by electrochemically controlling the redox state of the pendent diimide unit of the molecule in an ionic liquid. The electrical conductances of the dianion and neutral states differ by more than one order of magnitude. The potential-dependence of the charge-transport characteristics of the NDI molecules was confirmed by DFT calculations, which account for electrochemical double-layer effects on the conductance of the NDI junctions. This study suggests that integration of a pendant redox unit with strong coupling to a molecular backbone enables the tuning of charge transport through single-molecule devices by controlling their redox states.

16.
Cell Physiol Biochem ; 33(5): 1467-74, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24854431

RESUMEN

BACKGROUND: Bone marrow-derived mesenchymal stem cells (bmMSCs) are the most promising seed cells for cell transplant therapy. Hypoxia is a known stimulus of autophagy. Recent studies showed that hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells (CP-MSCs). However, whether hypoxia affects autophagy of bmMSCs has not been examined. The goal of this study was to investigate the effect of hypoxia on autophagy of mouse bmMSCs and the underlying mechanisms. METHODS: BmMSCs from mouse bone marrow were randomly divided into three groups: control (C), hypoxia (H) and hypoxia + reoxygenation (H+R) groups. Subsequent autophagic signals were analyzed by immunostaining and Western blot assays. RESULTS: The expression of autophagic signals LC-3, Atg5 and Beclin-1, as well as the conversion of LC3B-I to LC3B-II in bmMSCs were significantly increased in H group as compared with control (p<0.05). These autophagic signals were also higher in H+R group than in H group (p<0.05). Also, the expression of phospho-ERK1/2 was significantly increased in H and H+R groups as compared with control (p<0.05). Notably, application of ERK1/2 inhibitor U0126 (5µM) significantly repressed hypoxia-induced expression of LC-3 and Atg5, as well as conversion of LC3B-I to LC3B-II (p<0.05). CONCLUSION: Hypoxia can induce autophagy of bmMSCs, which depends on activation of ERK1/2 pathway.


Asunto(s)
Autofagia , Células de la Médula Ósea/citología , Hipoxia/patología , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Animales , Autofagia/efectos de los fármacos , Butadienos/farmacología , Células Cultivadas , Activación Enzimática , Células Madre Mesenquimatosas/enzimología , Ratones , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Nitrilos/farmacología
17.
Chemistry ; 20(45): 14614-8, 2014 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-25266337

RESUMEN

Two-dimensional covalent organic frameworks (2D COFs) provide a unique platform for the molecular design of electronic and optoelectronic materials. Here, the synthesis and characterization of an electroactive COF containing the well-known tetrathiafulvalene (TTF) unit is reported. The TTF-COF crystallizes into 2D sheets with an eclipsed AA stacking motif, and shows high thermal stability and permanent porosity. The presence of TTF units endows the TTF-COF with electron-donating ability, which is characterized by cyclic voltammetry. In addition, the open frameworks of TTF-COF are amenable to doping with electron acceptors (e.g., iodine), and the conductivity of TTF-COF bulk samples can be improved by doping. Our results open up a reliable route for the preparation of well-ordered conjugated TTF polymers, which hold great potential for applications in fields from molecular electronics to energy storage.


Asunto(s)
Compuestos Heterocíclicos/química , Benzaldehídos/química , Electroquímica , Conformación Molecular , Difracción de Rayos X
18.
Exp Cell Res ; 319(7): 1054-9, 2013 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-23399833

RESUMEN

The bone marrow-derived mesenchymal stem cells (bmMSCs) have been widely used in cell transplant therapy, and the proliferative ability of bmMSCs is one of the determinants of the therapy efficiency. Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) as a transmembrane protein is responsible for binding, internalizing and degrading oxidized low density lipoprotein (ox-LDL). It has been identified that LOX-1 is expressed in endothelial cells, vascular smooth muscle cells, cardiomyocytes, fibroblasts and monocytes. In these cells, low concentration of ox-LDL (<40 µg/mL) stimulates their proliferation via LOX-1 activation. However, it is poor understood that whether LOX-1 is expressed in bmMSCs and which role it plays. In this study, we investigated the status of LOX-1 expression in bmMSCs and its function on bmMSC proliferation. Our results showed that primary bmMSCs exhibiting a typical fibroblast-like morphology are positive for CD44 and CD90, but negative for CD34 and CD45. LOX-1 in both mRNA and protein levels is highly expressed in bmMSCs. Meanwhile, bmMSCs exhibit a strong potential to take up ox-LDL. Moreover, LOX-1 expression in bmMSCs is upregulated by ox-LDL with a dose- and time-dependent manner. Presence of ox-LDL also enhances the proliferation of bmMSCs. Knockdown of LOX-1 expression significantly inhibits ox-LDL-induced bmMSC proliferation. These findings indicate that LOX-1 plays a role in bmMSC proliferation.


Asunto(s)
Células de la Médula Ósea/metabolismo , Proliferación Celular , Lipoproteínas LDL/metabolismo , Células Madre Mesenquimatosas/metabolismo , Receptores Depuradores de Clase E/metabolismo , Animales , Células de la Médula Ósea/citología , Células Cultivadas , Células Endoteliales/metabolismo , Humanos , Lipoproteínas LDL/inmunología , Células Madre Mesenquimatosas/citología , Ratones , Receptores Depuradores de Clase E/inmunología
19.
Asian J Surg ; 47(2): 853-863, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38042663

RESUMEN

The aim was to evaluate the efficacy and safety between the watch-and-wait strategy (WW), radical surgery (RS), and local excision (LE) for rectal cancer with clinical complete response (cCR) after neoadjuvant radiotherapy (nCRT). We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trials to compare WW with RS and LE for patients with cCR until March 2023 and collected the following data: local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), overall survival (OS), and disease-free survival (DFS). In total, 2240 patients from 21 studies were included. Pairwise meta-analysis revealed no statistically significant differences between the three groups in terms of CRD and 2-, 3-, and 5-year OS (P < 0.05). The RS group was significantly better than the WW group in terms of the LR rate (odds ratio [OR] = 0.12, 95 % confidence interval [CI]: 0.06-0.21, P < 0.001, I2 = 0 %], 3-year DFS (OR = 1.56, 95 % CI: 1.10-2.21, P = 0.01, I2 = 38 %), and 5-year DFS (OR = 2.30, 95 % CI: 1.53-3.46, P < 0.001, I2 = 34 %). The results of network meta-analysis were also similar. After sensitivity analysis, the 5-year OS of the RS group was significantly better than that of the WW group (OR = 2.77, 95 % CI: 1.28-6.00, P = 0.009, I2 = 33 %). Nevertheless, neither regression analysis nor subgroup analysis provided meaningful results. However, the cumulative meta-analysis of LR, DM, and 3- and 5-year DFS revealed significant turning points (P < 0.05). Our meta-analysis recommends using the WW strategy for patients with cCR having poor underlying conditions and high surgical risk; however, there is a risk of higher LR and worse survival after 3 years.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Metaanálisis en Red , Quimioradioterapia , Espera Vigilante/métodos , Recurrencia Local de Neoplasia , Neoplasias del Recto/cirugía , Resultado del Tratamiento
20.
World J Gastroenterol ; 30(15): 2128-2142, 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38681988

RESUMEN

BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) in the presence of cirrhosis is unfavourable, primarily attributable to the high incidence of recurrence. AIM: To develop a machine learning model for predicting early recurrence (ER) of post-hepatectomy HCC in patients with cirrhosis and to stratify patients' overall survival (OS) based on the predicted risk of recurrence. METHODS: In this retrospective study, 214 HCC patients with cirrhosis who underwent curative hepatectomy were examined. Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods. Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses. Five machine learning methods were used for model comparison, aiming to identify the optimal model. The model's performance was evaluated using the receiver operating characteristic curve [area under the curve (AUC)], calibration, and decision curve analysis. Additionally, the Kaplan-Meier (K-M) curve was used to evaluate the stratification effect of the model on patient OS. RESULTS: Within this study, the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features. In the training cohort, this model attained an AUC of 0.844, while in the validation cohort, it achieved a value of 0.790. The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients' OS. CONCLUSION: The combined model, integrating both radiomics and clinical-radiologic characteristics, exhibited excellent performance in HCC with cirrhosis. The K-M curves assessing OS revealed statistically significant differences.


Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Cirrosis Hepática , Neoplasias Hepáticas , Aprendizaje Automático , Recurrencia Local de Neoplasia , Tomografía Computarizada por Rayos X , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Femenino , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Anciano , Tomografía Computarizada por Rayos X/métodos , Pronóstico , Valor Predictivo de las Pruebas , Curva ROC , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Estimación de Kaplan-Meier , Adulto , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Factores de Riesgo , Radiómica
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