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1.
Mol Med ; 30(1): 41, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519941

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.


Assuntos
Hiperplasia Prostática , Humanos , Masculino , Camundongos , Animais , Idoso , Hiperplasia Prostática/genética , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Fator de Necrose Tumoral alfa , Extratos Vegetais/farmacologia , Próstata/metabolismo , Próstata/patologia , Inflamação/patologia
2.
J Nanobiotechnology ; 22(1): 208, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664789

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Osteócitos , Osteogênese , Tropomiosina , Animais , Masculino , Camundongos , Adipogenia , Diferenciação Celular , Células Cultivadas , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Osteoclastos/metabolismo , Osteócitos/metabolismo , Osteoporose/metabolismo , Tropomiosina/metabolismo , Tropomiosina/genética
3.
Inflamm Res ; 72(10-11): 2053-2072, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37816881

RESUMO

OBJECTIVE: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. METHODS: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. RESULTS: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. CONCLUSIONS: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.


Assuntos
Artrite Experimental , Artrite Reumatoide , Camundongos , Animais , Prata/uso terapêutico , Osteogênese , Inflamação/tratamento farmacológico , Inflamação/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Colágeno , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Metaloproteinases da Matriz
4.
Physiol Plant ; 175(2): e13880, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36840627

RESUMO

At the outer canopy, the white leaves of Actinidia kolomikta can turn pink but they stay white in A. polygama. We hypothesized that the different leaf colors in the two Actinidia species may represent different photoprotection strategies. To test the hypothesis, leaf optical spectra, anatomy, chlorophyll a fluorescence, superoxide (O2 ˙- ) concentration, photosystem II photo-susceptibility, and expression of anthocyanin-related genes were investigated. On the adaxial side, light reflectance was the highest for white leaves of A. kolomikta, followed by its pink leaves and white leaves of A. polygama, and the absorptance for white leaves of A. kolomikta was the lowest. Chlorophyll and carotenoid content of white and pink leaves in A. kolomikta were significantly lower than those of A. polygama, while the relative anthocyanin content of pink leaves was the highest. Chloroplasts of palisade cells of white leaves in A. kolomikta were not well developed with a lower maximum quantum efficiency of PSII than the other types of leaves (pink leaves of A. kolomikta and white leaves of A. Polygama at the inner/outer canopy). After high light treatment from the abaxial surface, Fv /Fm decreased to a larger extent for white leaves of A. kolomikta than pink leaf and white leaves of A. polygama, and its non-photochemical quenching was also the lowest. White leaves of A. kolomikta showed higher O2 ˙- concentration compared to pink leaves under the same strong irradiance. The expression levels of anthocyanin biosynthetic genes in pink leaves were higher than in white leaves. These results indicate that white leaves of A. kolomikta apply a reflection strategy for photoprotection, while pink leaves resist photoinhibition via anthocyanin accumulation.


Assuntos
Actinidia , Actinidia/metabolismo , Clorofila A/análise , Antocianinas/metabolismo , Clorofila/metabolismo , Fotossíntese/fisiologia , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/metabolismo , Luz
5.
Int Wound J ; 20(8): 3131-3139, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37143445

RESUMO

This paper describes a modified method of applying unidirectional barbed sutures to treat the incisions of the single-port video-assisted thoracoscopic surgery (VATS) and discusses its safety and feasibility. This was a retrospective analysis of 108 patients who underwent single-port VATS admitted to the Department of Thoracic Surgery, the China-Japan Union Hospital of Jilin University, from April 2019 to April 2020. The experimental group (65 patients) was given unidirectional barbed sutures (V-Loc™ sutures) to treat the incision, and the control group (43 patients) had a skin stapler to treat the incision. The complications related to the incisions of the two groups were compared. There was no statistically significant difference between the experimental and control groups regarding incisional infection, incisional splitting, fat liquefaction, and incisional resewing. The pleural fluid outflow from the drainage orifice after removal of the chest tube (0 cases in the experimental group and 7 cases in the control group, P = 0.001) was significantly lower in the experimental group than in the control group. The scores of the scars showed that the experimental group was significantly better than the control group. The modified method of treating the incisions of the single-port VATS with V-Loc™ sutures has good efficacy and safety. It reduces the incidence of pleural fluid outflow from the drainage orifice after removal of the chest tube compared with the traditional stapler suture method, and it has superior cosmetic outcomes.


Assuntos
Cicatriz , Cirurgia Torácica Vídeoassistida , Humanos , Estudos Retrospectivos , Drenagem , Suturas
6.
J Cell Mol Med ; 25(12): 5525-5533, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33960660

RESUMO

Osteoporosis is one of the most common metabolic bone diseases affecting millions of people. We previously found that harmine prevents bone loss in ovariectomized mice via increasing preosteoclast platelet-derived growth factor-BB (PDGF-BB) production and type H vessel formation. However, the molecular mechanisms by which harmine promotes preosteoclast PDGF-BB generation are still unclear. In this study, we revealed that inhibitor of DNA binding-2 (Id2) and activator protein-1 (AP-1) were important factors implicated in harmine-enhanced preosteoclast PDGF-BB production. Exposure of RANKL-induced Primary bone marrow macrophages (BMMs), isolated from tibiae and femora of mice, to harmine increased the protein levels of Id2 and AP-1. Knockdown of Id2 by Id2-siRNA reduced the number of preosteoclasts as well as secretion of PDGF-BB in RANKL-stimulated BMMs administrated with harmine. Inhibition of c-Fos or c-Jun (components of AP-1) both reversed the stimulatory effect of harmine on preosteoclast PDGF-BB production. Dual-luciferase reporter assay analyses determined that PDGF-BB was the direct target of AP-1 which was up-regulated by harmine treatment. In conclusion, our data demonstrated a novel mechanism involving in the production of PDGF-BB increased by harmine, which may provide potential therapeutic targets for bone loss diseases.


Assuntos
Becaplermina/metabolismo , Medula Óssea/efeitos dos fármacos , Harmina/farmacologia , Proteína 2 Inibidora de Diferenciação/metabolismo , Macrófagos/efeitos dos fármacos , Osteoclastos/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Medula Óssea/metabolismo , Células Cultivadas , Alucinógenos/farmacologia , Proteína 2 Inibidora de Diferenciação/genética , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Osteoclastos/citologia , Fator de Transcrição AP-1/genética
7.
Angew Chem Int Ed Engl ; 60(10): 5299-5306, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33216437

RESUMO

Combining Ising-type magnetic anisotropy with collinear magnetic interactions in single-molecule magnets (SMMs) is a significant synthetic challenge. Herein we report a Dy[15-MCCu -5] (1-Dy) SMM, where a DyIII ion is held in a central pseudo-D5h pocket of a rigid and planar Cu5 metallacrown (MC). Linking two Dy[15-MCCu -5] units with a single hydroxide bridge yields the double-decker {Dy[15-MCCu -5]}2 (2-Dy) SMM where the anisotropy axes of the two DyIII ions are nearly collinear, resulting in magnetic relaxation times for 2-Dy that are approximately 200 000 times slower at 2 K than for 1-Dy in zero external field. Whereas 1-Dy and the YIII -diluted Dy@2-Y analogue do not show remanence in magnetic hysteresis experiments, the hysteresis data for 2-Dy remain open up to 6 K without a sudden drop at zero field. In conjunction with theoretical calculations, these results demonstrate that the axial ferromagnetic Dy-Dy coupling suppresses fast quantum tunneling of magnetization (QTM). The relaxation profiles of both complexes curiously exhibit three distinct exponential regimes, and hold the largest effective energy barriers for any reported d-f SMMs up to 625 cm-1 .

8.
Oral Dis ; 26(5): 998-1009, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32144839

RESUMO

OBJECTIVES: We aimed to investigate whether skeletal-specific H-type blood vessels exist in alveolar bone and how they function in alveolar bone remodeling. MATERIALS AND METHODS: H-type vessels with high expression of CD31 and Endomucin (CD31hi Emcnhi ) were immunostained in alveolar bone. Abundance and age-related changes in CD31hi Emcnhi endothelial cells (H-ECs) were detected by flow cytometry. Osteoprogenitors association with H-type vessels and bone mass were detected in tooth extraction model of alveolar bone remodeling by immunohistofluorescence and micro-CT, respectively. Transcription and expression of H-EC feature genes during in vitro Notch inhibition were measured by RT-qPCR and immunocytofluorescence. RESULTS: We verified that H-type vessels existed in alveolar bone, the abundance of which was highest at infancy age, then decreased but maintained a constant level during aging. In tooth extraction model, H-ECs significantly increased with concomitant perivascular accumulation of Runx2+ osteoprogenitors and gradually augmentation of bone mass. Notch inhibition of in vitro cultured H-ECs resulted in decreased expression levels of Emcn and hes1, but not Pecam1 or Kdr genes, with decreased expression levels of H-EC numbers, accordingly. CONCLUSIONS: The present study suggests that H-type vessels promote osteogenesis during alveolar bone remodeling. Notch signaling pathway regulates expression of Emcn and possibly determines fate and functions of alveolar H-ECs.


Assuntos
Remodelação Óssea , Células Endoteliais , Osteogênese , Extração Dentária , Animais , Camundongos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética
9.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4820-4829, 2019 Nov.
Artigo em Zh | MEDLINE | ID: mdl-31872588

RESUMO

Agkistrodon acutus is a traditional Chinese herb medicine which has immunological regulation,anti-tumor,anti-inflammatory and analgesic effects,which is mainly used for the treatment of rheumatoid arthritis,ankylosing spondylitis,sjogren's syndrome and tumors. In order to excavate more important functional genes from A. acutus,the transcriptome of the venom gland was sequenced by the Illumina Hi Seq 4000,and 32 862 unigenes were assembled. Among them,26 589 unigenes were mapped to least one public database. 2 695 unigenes were annotated and assigned to 62 TF families,and 5 920 SSR loci were identified. The majority of mapped unigenes was from Protobothrops mucrosquamatus in the NR database,which revealed their closest homology. Three secretory phospholipase A_2 with different amino acid sequences showed similar spatial structures and all had well-conserved active sites. The 3 D structural models of C-type lectin showed conserved glycosylation binding sites( Asn45). This study will lay the foundation for the further study of the function of snake venom protein,and promoting the development and utilization of genome resources from A. acutus.


Assuntos
Agkistrodon/genética , Venenos de Crotalídeos , Venenos de Serpentes/genética , Animais , Perfilação da Expressão Gênica , Serpentes , Transcriptoma
10.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2753-2761, 2019 Jul.
Artigo em Zh | MEDLINE | ID: mdl-31359687

RESUMO

Chlorophyll content,leaf mass to per area,net photosynthetic rate and bioactive ingredients of Asarum heterotropoides var. mandshuricum,a skiophyte grown in four levels of solar irradiance were measured and analyzed in order to investigate the response of photosynthetic capability to light irradiance and other environmental factors. It suggested that the leaf mass to per area of plant was greatest value of four kinds of light irradiance and decreasing intensity of solar irradiance resulted in the decrease of leaf mass to per area at every phenological stage. At expanding leaf stage,the rate of Chla and Chlb was 3. 11 when A. heterotropoides var. mandshuricum grew in full light irradiance which is similar to the rate of heliophytes,however,the rate of Chla and Chlb was below to 3. 0 when they grew in shading environment. The content of Chla,Chlb and Chl( a+b) was the greatest value of four kinds of light irradiance and decreasing intensity of solar irradiance resulted in its decreasing remarkably( P<0. 05). The rate of Chla and Chlb decreased but the content of Chla,Chlb and Chl( a+b) increased gradually with continued shading. The maximum value of photosynthetically active radiation appeared at 10: 00-12: 00 am in a day. The maximum value of net photosynthetic rate appeared at 8: 30-9: 00 am and the minimum value appeared at 14: 00-14: 30 pm at each phenological stage if plants grew in full sunlight. However,when plants grew in shading,the maximum value of net photosynthetic rate appeared at about 10: 30 am and the minimum value appeared at 12: 20-12: 50 pm at each phenological stage. At expanding leaf stage and flowering stage,the average of net photosynthetic rate of leaves in full sunlight was remarkably higher than those in shading and it decreased greatly with decreasing of irradiance gradually( P < 0. 05). However,at fruiting stage,the average of net photosynthetic rate of leaves in full sunlight was lower than those in 50% and 28% full sunlight but higher than those in 12% full sunlight. All photosynthetic diurnal variation parameters of plants measured in four kinds of different irradiance at three stages were used in correlation analysis. The results suggested that no significant correlation was observed between net photosynthetic rate and photosynthetically active radiation,and significant negative correlation was observed between net photosynthetic rate and environmental temperature as well as vapor pressure deficit expect for 12% full sunlight. Positive correlation was observed between net photosynthestic rate and relative humidity expect for 12% full sunlight. Significant positive correlation was observed between net photosynthetic rate and stomatal conductance in the four light treatments. Only,in 12% full sunlight,the net photosynthetic rate was significantly related to photosynthetically active radiation rather than related to environmental temperature,vapor pressure deficit and relative humidity. In each light treatment,a significant positive correlation was observed between environmental temperature and vapor pressure deficit,relative humidity as well as stomatal conductance. Volatile oil content was 1. 46%,2. 16%,1. 56%,1. 30% respectively. ethanol extracts was 23. 44%,22. 45%,22. 18%,21. 12% respectively. Asarinin content was 0. 281%,0. 291%,0. 279% and 0. 252% respectively. The characteristic components of Asarum volatile oil of plant in different light treatments did not change significantly among different groups.


Assuntos
Asarum/fisiologia , Asarum/efeitos da radiação , Fotossíntese , Luz Solar , Clorofila/análise , Folhas de Planta/efeitos da radiação
11.
Cell Physiol Biochem ; 50(3): 1068-1083, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30355920

RESUMO

BACKGROUND/AIMS: Recently, we and others showed that the relative abundance of a specific vessel subtype, strongly positive for CD31 and Endomucin (CD31hiEmcnhi), is associated with bone formation and bone loss, and platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces the formation of the specific vessels and thereby stimulates osteogenesis. Inhibition of Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) has been shown to block the fusion of preosteoclasts into mature osteoclasts. However, it is unclear whether inhibition of SHP-2 could promote preosteoclast-induced angiogenesis and then enhance bone formation. This study aimed to determine the effects of a specific SHP-2 inhibitor (NSC-87877) on CD31 hiEmcnhi vessel and bone formation. METHODS: 3-month-old C57BL/6 mice were subjected to either ovariectomy (OVX) or sham operation. OVX mice were intraperitoneally injected with NSC-87877 and the control (sham) mice were treated with an equal volume of diluents (PBS). Two months later, bone samples from mice were collected for µCT, histological, immunohistochemical and immunofluorescent analyses to assess bone mass, osteogenic and osteoclastic acitivities, as well as the densities of CD31hiEmcnhi vessels. A series of angiogenesis- related assays were performed to test the effects of NSC-87877 on the pro-angiogenic activities of preosteoclasts in vitro. RESULTS: We found that NSC-87877 is sufficient to induce bone-sparing effects in OVX-induced osteoporotic mouse model. We also found that NSC-87877 induces higher numbers of preosteoclasts and CD31hiEmcnhi vessels and higher levels of PDGF-BB in bone marrow of osteoporotic mice. In vitro assays showed that NSC-87877 prevents preosteoclast fusion, increases PDGF-BB production, and augments the pro-angiogenic abilities of preosteoclasts. CONCLUSION: Our results suggest that NSC-87877 can be used as a promising therapeutic agent for osteoporosis by inhibiting osteoclast formation and promoting preosteoclast-induced angiogenesis.


Assuntos
Osteogênese/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Quinolinas/farmacologia , Animais , Becaplermina , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Osteoporose/patologia , Osteoporose/prevenção & controle , Osteoporose/veterinária , Ovariectomia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteínas Proto-Oncogênicas c-sis/metabolismo , Quinolinas/uso terapêutico , Ligante RANK/metabolismo , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Microtomografia por Raio-X
12.
Cell Biol Int ; 42(5): 580-588, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29323455

RESUMO

Osteosarcoma represents the most common primary malignant bone tumor in children and adolescents, which shows severe resistance toward standard chemotherapy because of high invasive capacity and growing incidence. Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. However, little information about SeC-induced growth inhibition against human osteosarcoma is available. Herein, the anticancer efficiency and underlying mechanism of SeC against human osteosarcoma were evaluated in vitro and in vivo. The results revealed that SeC significantly inhibited MG-63 human osteosarcoma cells growth in vitro through induction of S-phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK-2, PARP cleavage, and caspases activation. SeC treatment also resulted in mitochondrial dysfunction through affecting Bcl-2 family expression. Moreover, SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS) overproduction. ROS inhibition effectively blocked SeC-induced cytotoxicity and p53 phosphorylation. Importantly, MG-63 human osteosarcoma xenograft growth in nude mice was significantly suppressed in vivo through triggering apoptosis and p53 phosphorylation. These results indicated that SeC had the potential to inhibit human osteosarcoma cells growth in vitro and in vivo through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation, which validated the potential application of Se-containing compounds in treatment of human osteosarcoma.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Selenocisteína/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Antineoplásicos/uso terapêutico , Apoptose , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos Nus , Mitocôndrias/metabolismo , Osteossarcoma/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Selenocisteína/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Am Chem Soc ; 139(1): 373-380, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-27936686

RESUMO

The pursuit of single-molecule magnets (SMMs) with better performance urges new molecular design that can endow SMMs larger magnetic anisotropy. Here we report that two-coordinate cobalt imido complexes featuring highly covalent Co═N cores exhibit slow relaxation of magnetization under zero direct-current field with a high effective relaxation barrier up to 413 cm-1, a new record for transition metal based SMMs. Two theoretical models were carried out to investigate the anisotropy of these complexes: single-ion model and Co-N coupling model. The former indicates that the pseudo linear ligand field helps to preserve the first-order orbital momentum, while the latter suggests that the strong ferromagnetic interaction between Co and N makes the [CoN]+ fragment a pseudo single paramagnetic ion, and that the excellent performance of these cobalt imido SMMs is attributed to the inherent large magnetic anisotropy of the [CoN]+ core with |MJ = ± 7/2⟩ ground Kramers doublet.

14.
Cell Physiol Biochem ; 43(1): 320-330, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28854422

RESUMO

BACKGROUND/AIMS: This study aimed to explore the effects of the long non-coding RNA HOST2 (lnc-HOST2) on the proliferation, migration, invasion and apoptosis of osteosarcoma cells. METHODS: Osteosarcoma tissues and adjacent normal tissues from 52 patients were selected. Human osteosarcoma cell lines (SaOS2, HOS, U2OS and MG-63) were collected and cultured; MG-63 cells had the highest lnc-HOST2 expression and thus were used in subsequent experiments. Then, MG-63 cells were transfected and divided into the blank (no transfection), si-CON (transfected with negative control siRNA) and si-lnc-HOST2 (transfected with small interference lnc-HOST2 siRNA) groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of lnc-HOST2 in primary tissues and cells. Cell growth was detected using the CCK-8 and colony formation assays. Cell doubling time was detected. Cell migration and invasion were observed using the scratch test and Transwell assays. Cell apoptosis and cell cycle progression of osteosarcoma cells were detected using flow cytometry with annexin V/PI double staining and PI staining, respectively. RESULTS: The level of lnc-HOST2 expression in the si-lnc-HOST2 group was significantly decreased compared to that in the blank and si-CON groups. The OD values in the si-lnc-HOST2 group were significantly lower than those in the blank and si-CON groups. Compared to the blank and si-CON groups, the si-lnc-HOST2 group presented significant decreases in the colony number and healing rates after scratching. The number of invasive cells in the si-lnc-HOST2 group was significantly less than that in the blank and si-CON groups. In the si-lnc-HOST2 group, the cell cycle was mainly halted in the G1 phase, and the apoptosis rate and doubling time in this group were significantly higher than those in the blank group and si-CON group. CONCLUSIONS: Inhibition of lnc-HOST2 could suppress the proliferation, migration, and invasion and promote the apoptosis of osteosarcoma cells.


Assuntos
Neoplasias Ósseas/patologia , Osteossarcoma/patologia , RNA Longo não Codificante/metabolismo , Adolescente , Apoptose , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Criança , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Masculino , Osteossarcoma/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo
15.
Heart Lung Circ ; 26(1): 94-100, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27425182

RESUMO

BACKGROUND: Degradable collagen-chitosan composite materials have been used to fabricate tissue engineered heart valves. The aims of this study were to demonstrate that the collagen-chitosan composite scaffolds are cytocompatible, and endothelial cells can be differentiated from bone marrow mesenchymal stem cells (BMSCs) when seeded onto the scaffolds. The adhesion and biological activities of the seeded cells were also investigated. METHODS: Collagen-chitosan composite material was used as the cell matrix, and smooth muscle cells, fibroblasts and BMSCs were used as seed cells. After four weeks of in vitro culture, the smooth muscle cells, fibroblasts, and BMSCs were sequentially seeded into the collagen-chitosan composite material. After four weeks in culture, the cellular density and activity were assessed on segments of the tissue engineered heart valve scaffolds to determine the cell viability and proliferation in the collagen-chitosan composite material. RESULTS: The tissue engineered heart valves stained positively for both smooth muscle actin and endothelial cell factor VIII, suggesting that the seeded cells were in fact smooth muscle cells, fibroblasts, and endothelial cells. The 6-ketone prostaglandin content, as measured by radioimmunoassay, of the collagen-chitosan cell culture fluid was higher than that of the serum-free medium (P <0.01). Light and electron microscopy showed that the seeded cells had shapes similar to the morphology of smooth muscle cells, fibroblasts, and endothelial cells. CONCLUSIONS: Endothelial cells can be differentiated from BMSCs when seeded onto the collagen-chitosan composite scaffolds. The seeded cells retained their biological activity after being cultured in vitro and seeded into the collagen-chitosan composite material.


Assuntos
Implantes Absorvíveis , Quitosana/química , Colágeno/química , Fibroblastos/metabolismo , Valvas Cardíacas , Miócitos de Músculo Liso/metabolismo , Engenharia Tecidual , Animais , Células Cultivadas , Fibroblastos/classificação , Miócitos de Músculo Liso/citologia , Coelhos
16.
Clin Lab ; 62(5): 947-53, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27349023

RESUMO

BACKGROUND: Several lines of evidence suggest that slow coronary flow (SCF) phenomenon seems to be an early form of atherosclerosis and low-grade inflammation plays a role in the development of SCF. Interleukin-6 (IL-6) is a pleiotropic cytokine, functions as a mediator of inflammatory response, and has both pro-inflammatory and anti-inflammatory properties. The aim of the present study is to investigate the relationship between IL-6 -634C/G polymorphism and SCF in Han Chinese. METHODS: 250 subjects who underwent coronary angiography and had normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. 41 patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and 209 subjects within normal limits served as normal coronary flow (NCF) group. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes. RESULTS: The distribution of the IL-6 -634C/G genotypes (CC, CG, and GG) was 56.94%, 37.80%, and 5.26% in the NCF subjects, and 36.59%, 48.78%, and 14.63% in the SCF group, respectively (p = 0.0173). The frequency of the G allele in the SCF (39.02%) group was significantly higher than that in the NCF (24.16%) group (p = 0.0054). Compared with the CC genotype, the G allele carriers (CG + GG genotypes) had increased risk of SCF in both unadjusted and adjusted analyses. In SCF patients, the average serum IL-6 levels (pg/mL) in CG + GG genotype (4.78 ± 0.42) were statistically higher than in CC genotype (3.93 ± 0.36) (p = 0.0000). CONCLUSIONS: Our data support that IL-6 -634C/G polymorphism is associated with SCF and the G allele has increased risk for SCF in Han Chinese.


Assuntos
Circulação Coronária , Interleucina-6/genética , Fenômeno de não Refluxo/genética , Polimorfismo Genético , Idoso , Feminino , Genótipo , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fenômeno de não Refluxo/sangue , Fenômeno de não Refluxo/etiologia , Regiões Promotoras Genéticas
17.
Macromol Rapid Commun ; 36(5): 490-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25619384

RESUMO

Low-molecular-weight poly(ethylene glycol) (PEG) is deliberately incorporated into synthesized swellable poly(ethylene oxide) (PEO) membranes via a facile post-treatment strategy. The membranes exhibit both larger fractional free volume (FFV) and a higher content of CO2-philic building units, resulting in significant increments in both CO2 permeability and CO2/H2 selectivity. The separation performance correlates nicely with the microstructure of the membranes. This study may provide useful insights in the formation and mass transport behavior of highly efficient polymeric membranes applicable to clean energy purification and CO2 capture, and possibly bridge the material-induced technology gap between academia and industry.


Assuntos
Dióxido de Carbono/isolamento & purificação , Membranas Artificiais , Polietilenoglicóis/química , Polímeros/química , Transporte Biológico , Dióxido de Carbono/química , Peso Molecular , Permeabilidade
18.
Sex Med ; 12(1): qfae010, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505341

RESUMO

Background: The causal relationship between certain lifestyle factors and erectile dysfunction (ED) is still uncertain. Aim: The study sought to investigate the causal effect of 9 life factors on ED through 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR). Methods: Genetic instruments to proxy 9 risk factors were identified by genome-wide association studies. The genome-wide association studies estimated the connection of these genetic variants with ED risk (n = 223 805). We conducted SVMR, inverse variance-weighting, Cochran's Q, weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MVMR analyses to explore the total and direct relationship between life factors and ED. Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED. Results: In SVMR analyses, suggestive associations with increased the risk of ED were noted for ever smoked (odds ratio [OR], 5.894; 95% confidence interval [CI], 0.469 to 3.079; P = .008), alcohol consumption (OR, 1.495; 95% CI, 0.044 to 0.760; P = .028) and body mass index (BMI) (OR, 1.177; 95% CI, 0.057 to 0.268; P = .003). Earlier age at first intercourse was significantly related to reduced ED risk (OR, 0.659; 95% CI, -0.592 to -0.244; P = 2.5 × 10-6). No strong evidence was found for the effect of coffee intake, time spent driving, physical activity, and leisure sedentary behaviors on the incidence of ED (All P > .05). The result of MVMR analysis for BMI (OR, 1.13; 95% CI, 1.01 to 1.25; P = .045) and earlier age at first intercourse (OR, 0.77; 95% CI, 0.56 to 0.99; P = .018) provided suggestive evidence for the direct impact on ED, while no causal factor was detected for alcoholic drinks per week and ever smoked. Clinical implications: This study provides evidence for the impact of certain modifiable lifestyle factors on the development of ED. Strengths and limitations: We performed both SVMR and MVMR to strengthen the causal relationship between exposures and outcomes. However, the population in this study was limited to European ancestry. Conclusion: Ever smoked, alcoholic drinks per week, BMI, and age first had sexual intercourse were causally related to ED, while the potential connection between coffee intake, physical activity, recreational sedentary habits, and increased risk of ED needs to be further confirmed.

19.
Int J Biol Macromol ; 253(Pt 6): 127267, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37820903

RESUMO

Diabetes mellitus (DM) as one chronic metabolic disease was greatly increased over recent decades. The major agents treating diabetes have noticeable side effects as well as the tolerability problems. The bioactive dietary polysaccharides from abundant natural resources exhibit good hypoglycemic effect with rare adverse effects, which might serve as a candidate to prevent and treat diabetes. However, the correlations between the hypoglycemic mechanism of polysaccharides and their structure were not mentioned in several studies, what's more, most of the current hypoglycemic studies on polysaccharides were based on in vitro and in vivo experiments, and there was a lack of knowledge about the effects in human clinical trials. The aim of this review is to discuss recent literature about the variety of dietary polysaccharides with hypoglycemic activity, as well the mechanism of action and the structure-function relationship are highlighted. Meanwhile, the application of dietary polysaccharides in functional foods and clinical medicine are realized with an in-depth understanding. So as to promote the exploration of dietary polysaccharides in low glycemic healthy foods or clinical medicine to prevent and treat diabetes.


Assuntos
Diabetes Mellitus , Hipoglicemiantes , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Diabetes Mellitus/tratamento farmacológico , Carboidratos da Dieta/uso terapêutico , Alimento Funcional
20.
Front Med (Lausanne) ; 10: 1170520, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293306

RESUMO

Background: Hemoporfin-mediated photodynamic therapy (PDT) is an effective treatment for port-wine stains (PWS), and pain is the main adverse effect of this therapy. General anesthesia is commonly used for pain management during PDT, but the effect of general anesthetics on the subsequent treatment efficacy of PDT in PWS has not been reported. Objectives: To assess the use of general anesthesia combined with PDT compared with PDT alone in 207 PWS patients, and to provide further safety and efficacy data on this combined therapy. Methods: Propensity score matching (PSM) was used at a 2:1 ratio to create a general anesthetic group (n = 138) and a highly comparable nonanesthetic group (n = 69). The clinical outcomes were evaluated, and the treatment reactions and adverse effects were recorded after one treatment with PDT. Results: After matching, there was no significant difference in the demographic data of the patients in the two groups (p > 0.05), while the treatment efficacy was significantly higher in the general anesthetic group than in the nonanesthetic group (76.81 vs. 56.52%, p < 0.05). Moreover, logistic regression analysis confirmed that patients receiving general anesthesia showed an association with a good response to PDT (OR = 3.06; 95% CI, 1.57-6.00; p = 0.0011). Purpura lasted longer in the general anesthetic group, but the other treatment reactions and adverse effects were similar in the two groups (p > 0.05). No serious systemic adverse reactions were observed. Conclusion: We recommend this combined therapy, which is associated with painless, as a high efficacy treatment option for PWS patients, especially for patients with a poor response to multiple PDT alone treatments.

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