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1.
Medicine (Baltimore) ; 101(18): e29224, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35550474

RESUMO

RATIONALE: Polymorphous low-grade adenocarcinoma is a low-risk infiltrative malignant tumor of the salivary glands. However, some of these tumors are more malignant than the low-grade tumors and therefore, according to the most recent recommendation of the World Health Organization, they are renamed as polymorphous adenocarcinomas (PACs). Primary polymorphous low-grade adenocarcinomas/PACs of the lungs are rare. Herein, we report a case of primary PAC of the lung with bronchial cartilage and perineural invasion, and lymph node metastasis. PATIENT CONCERNS: A 58-year-old man had developed fever half a month prior, without chills or other accompanying symptoms, and the underlying reasons were unknown. His self-measured temperature was up to 39°C, accompanied by cough and expectoration, yellow and thin sputum, and shortness of breath. The patient's general state was normal, and respiratory sounds originating from the right lung were weak. Enhancement computed tomography revealed that the bronchial lumen of the basal segment of the lower lobe of the right lung was narrow; soft tissue density nodules were seen, with a range of approximately 2.4 cm × 1.3 cm. DIAGNOSIS: Based on clinical information, morphological features, and immunohistochemistry results, the pathological diagnosis was primary PAC of the lungs. INTERVENTION: Thoracoscopic resection of the middle and lower lobes of the right lung was performed, further extended dissection of the mediastinal lymph nodes was performed. OUTCOMES: The postoperative course was uneventful. LESSONS: Primary PAC of the lung is rare and may cause misdiagnosis. When encountering a lung tumor with diverse tissue structures, uniform cell type and nerve invasion, we should consider the possibility of PAC. Morphological and immunohistochemical features can be useful for diagnosing primary PAC of the lungs.

2.
BMC Musculoskelet Disord ; 22(1): 580, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167511

RESUMO

BACKGROUND: Revisions are mainly caused by wear debris-induced aseptic loosening. How to effectively suppress debris-induced periprosthetic osteolysis has become an urgent problem. Both zoledronic acid and teriparatide can increase the bone mass around prostheses and increase the stability of prostheses. A hypothesis was proposed: the combination of the two drugs may have a better treatment effect than the use of either drug alone. METHODS: We created a rabbit model to study the effect and mechanism of the combination of zoledronic acid and teriparatide in the treatment of aseptic loosening. Thirty-two adult male New Zealand white rabbits were selected and treated with TKA surgery, and a titanium rod prosthesis coated evenly with micrometre-sized titanium debris was implanted into the right femoral medullary cavity. All rabbits were randomized into four groups (control group = 8, zoledronic acid group = 8, teriparatide group = 8, and zoledronic acid + teriparatide group = 8). All the animals were sacrificed in the 12th week, and X-ray analyses, H&E staining, Goldner-Masson trichrome staining, von Kossa staining, and RT-PCR and Western blotting of the mRNA and protein of OCN, OPG, RANKL and TRAP5b in the interface membrane tissues around the prostheses were immediately carried out. RESULTS: The results shown that both zoledronic acid and teriparatide could inhibit debris-induced peri-prosthetic osteolysis and promote new bone formation. Zoledronic acid was more capable of inhibiting osteoclast activation and peri-prosthetic osteolysis, while teriparatide was more capable of promoting osteoblast function and peri-prosthetic bone integration. CONCLUSION: This research confirmed that the combination of zoledronic acid and teriparatide could prevent and treat aseptic loosening of the prosthesis more effectively. However, the safety of this combination and the feasibility of long-term application have not been ensured, and the clinical application requires further experiments and clinical research support.


Assuntos
Osteólise , Teriparatida , Animais , Masculino , Osteoclastos , Osteólise/tratamento farmacológico , Osteólise/etiologia , Osteólise/prevenção & controle , Falha de Prótese , Coelhos , Titânio , Ácido Zoledrônico
3.
Chem Asian J ; 16(14): 1918-1924, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-33960138

RESUMO

Two Cp*-RhIII based trefoil knots were obtained in high yield under ambient conditions via the coordination-driven self-assembly of semi-rigid thioether dipyridyl ligand 1,4-bis[(pyridin-4-ylthio)methyl]benzene (L1 ), ligand chloranilic acid (H2 -CA) and 6,11-dihydroxytetracene-5,12-dione (H2 -TtDo) with Cp*RhIII metal corner units, respectively. Furthermore, using the bulkier 4,4'-{[(2,5-dimethyl-1,4-phenylene)bis(methylene)]bis(sulfanediyl)}dipyridine (L2 ) in the place of ligand L1 in the construction process resulted in the formation of a teranuclear metallacycle and a template-free Borromean ring in high yields thanks to significantly altered intermolecular forces between the constituent ligands induced by the sterically-hindering methyl groups of L2 , as demonstrated via a detailed X-ray crystallographic analysis and NMR spectroscopy.

4.
Angew Chem Int Ed Engl ; 60(28): 15466-15471, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33871131

RESUMO

A Cp*-Rh based D-shaped binuclear metallacycle and a template-free molecular Borromean ring (BR) were obtained in high yield using the semi-rigid thioether dipyridyl ligand 1,4-bis[(pyridin-4-ylthio)methyl]benzene (Bptmb). The topological transformation from a binuclear metallacycle and a BR to tetranuclear metallacycles was realized via the controlled oxidation of thioethers. The strategy used in this work can be regarded as a new form of stimuli-responsive post-synthesis modification (PSM).

5.
J Am Chem Soc ; 143(2): 1119-1125, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33382617

RESUMO

Two molecular metalla-knots containing over 500 non-hydrogen atoms (especially 16 RhIII ions) and one molecular Borromean ring were obtained in high yields facilitated by multiple intermolecular interactions between their components. The syntheses rely on the strategic selection of the nonlinear dipyridyl ligand 2,7-di(pyridin-4-yl)-9H-fluorene (L1) as precursor, and the structures of the assemblies were confirmed by detailed X-ray crystallographic analysis. Subsequently, replacing L1 with the bulkier ligand 4,4'-(9,9-dimethyl-9H-fluorene-2,7-diyl)dipyridine (L2) led to the formation of three tetranuclear metallocycles in high yields on account of the weakened π-π stacking interactions between the naphthacene/anthracene and fluorene moieties, which in turn confirmed the significance of stacking interactions in the construction of the molecular 818 metalla-knots and the molecular Borromean ring.

6.
BMC Musculoskelet Disord ; 21(1): 775, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33234136

RESUMO

BACKGROUND: The major causes of failure after total knee arthroplasty (TKA) include prosthesis loosening and infection. This study aimed to investigate the role of carboxymethyl chitosan (CMC) in knee arthroplasty. METHODS: A total of 20 New Zealand white rabbits that were divided into two groups (10 in the control group and 10 in the chitosan group) were included in the study. They underwent TKA surgery, and all were implanted with titanium rod prostheses; the prosthesis in the chitosan group was coated with CMC. After 12 weeks, all rabbits were euthanized, and the following analyses of some specific surface membrane tissues around the prosthesis were performed: X-ray analysis; micro-computed tomography scan; haematoxylin and eosin, Van Gieson, and Von Kossa staining; reverse transcription polymerase chain reaction; and Western Blotting. RESULTS: The result of CCK8 test showed CMC can promote cell proliferation and increase cell viability. Radiological result showed better amount of bone deposits and more bone formation in the chitosan group. HE staining result showed CMC reduces inflammation around the prosthesis. The VG and Von Kossa staining results showed CMC can promote bone deposition around prosthesis. And according to the results of PCR and WB, the OCN content was higher in the chitosan group, while the MMPs content was lower. The chitosan group has an increased OPG/RANKL ratio than the control group. CONCLUSION: CMC can effectively inhibit the inflammatory response around the prosthesis and osteoclast activation and promote osteogenesis by interfering with the osteoprotegerin/receptor activator of nuclear factor kappa-Β ligand/receptor activator of nuclear factor kappa-Β signalling pathway.


Assuntos
Artroplastia do Joelho , Quitosana , Animais , Artroplastia do Joelho/efeitos adversos , Inflamação/tratamento farmacológico , Osteogênese , Osteoprotegerina , Ligante RANK , Coelhos , Microtomografia por Raio-X
7.
Orthop Surg ; 12(6): 1843-1853, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33094903

RESUMO

OBJECTIVE: To compare the postoperative inflammation and pain response between medial pivot (MP) and posterior stabilized (PS) prostheses among total knee arthroplasty (TKA) patients. METHODS: A prospective cohort study was conducted from January 2019 to May 2019 at the Affiliated Hospital of Qingdao University. The study included patients diagnosed with stage III or IV Kellgren-Lawrence knee osteoarthritis (KOA) who had failed conservative treatment, had undergone no previous knee surgeries, had varus substantial deformities (11°-20° deviation), and had received their first unilateral TKA. A total of 109 patients who underwent PS prosthesis TKA and 98 patients who underwent MP prosthesis TKA were continuously enrolled. Inflammation biomarkers, such as leukocyte (white blood cells), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), together with hemoglobin (Hb), the visual analog pain score (VAS) and range of motion (ROM) were compared between the two groups. The Student t-test was applied to analyze continuous parameters, and the χ2 -test was used for categorical parameters. The linear mixed model was used for the repeated measurement data from the follow-up visits. Multivariate backward logistic and linear regression models were used to determine the factors potentially influencing prostheses and VAS scores. RESULTS: All these enrolled patients were followed up at 2, 4, 7, and 30 days after TKA. There were no significant differences between the PS group and the MP group in body mass index (BMI), gender, laterality, usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, and drain tube extubation time (P > 0.05). Compared with the PS group, the MP group were older (67.5 years vs 65.4 years), and had a higher mid-vastus approach rate (67.3% vs 26.6%), a shorter tourniquet duration (68.3 ± 10.2 h vs 73.9 ± 11.2 h), a larger prosthetic pad (10.8 ± 1.2 mm vs 10.4 ± 1.2 mm), and a lower drain tube diversion volume (187.6 ± 119.3 mL vs 234.0 ± 155.7 mL). In the linear mixed model, MP prostheses had less CRP and ESR elevation and less Hb decrease than PS prostheses (P for group × time < 0.001). There were no significant differences in the changing trends between MP and PS prostheses by time for VAS scores and ROM. In the multivariate logistic regression model, MP prostheses showed significant differences compared with PS prostheses in treatment approach (odds ratio [OR] = 3.371, 95% confidence interval [CI]: 1.953-7.127; P < 0.001), ultrasound treatment start time (OR = 2.669, 95% CI: 1.385-5.141; P = 0.003), and tourniquet duration (OR = 0.954, 95% CI: 0.925-0.984; P = 0.003). Higher VAS scores on the second day postoperatively were related to high VAS scores preoperatively, use of opioids, high drain tube diversion, long tourniquet duration, and long drain tube extubation (P < 0.05), respectively. CONCLUSION: The MP prostheses showed potential advantages compared with PS prostheses in TKA in inflammatory responses.


Assuntos
Artroplastia do Joelho/instrumentação , Inflamação/sangue , Prótese do Joelho , Desenho de Prótese , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Amplitude de Movimento Articular , Torniquetes
8.
J Am Chem Soc ; 141(40): 16057-16063, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31509410

RESUMO

A template-free Cp*Ir-based molecular Solomon link and an unusual trefoil knot induced by stacking interactions were realized via selection of the nonrigid dipyridyl ligand 4,4'-bis(pyridin-4-ylmethyl)-1,1'-biphenyl (BpmBp). In addition, a novel heterobimetallic tetranuclear (IrIII2 + AgI2) complex featuring argentophilic interaction was synthesized in high yield. Remarkably, the reversible topological transformation between the Solomon link and an unusual trefoil knot can be achieved by utilizing the chemical reactivity of silver(I) ions under mild conditions, as demonstrated by a detailed X-ray crystallographic study.

10.
Chemistry ; 24(71): 18913-18921, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30430671

RESUMO

A series of metallosupramolecular architectures have been prepared, including rectangles, prisms and cages, that feature half-sandwich rhodium(III) fragments at the vertices. Remarkably, a stable cage-like heteropolymetallic complex possessing eight rhodium(III) and two silver(I) metal ions (3) has been obtained following a multistep procedure. The RhIII /AgI mixed macrocage enables the separation of dihalogenated benzene derivatives with high selectivity. Furthermore, a detailed X-ray crystallographic study confirmed that the discriminative encapsulation of para-dihalobenzene (dichlorobenzene, dibromobenzene and diiodobenzene) is favored by Ag-π interactions and steric effects.

11.
Int J Mol Med ; 42(6): 3640, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30320334

RESUMO

The authors have requested that their research article entitled 'Piezo1 protein induces the apoptosis of human osteoarthritis­derived chondrocytes by activating caspase­12, the signaling marker of ER stress' published in International Journal of Molecular Medicine 40, 845­853, 2017, be retracted from the journal. Following the publication of this article, an interested reader drew to our attention that certain of the figures, or figure parts, published in this article contained data that also appeared at around the same time in a publication featuring several of the same authors in Experimental Cell Research: Li XF, Leng P, Zhang Z and Zhang HN: 'The Piezo1 protein ion channel functions in human nucleus pulposus cell apoptosis by regulating mitochondrial dysfunction and the endoplasmic reticulum stress signal pathway'. Exp Cell Res 358: 377­389, 2017. Though these studies were performed in osteoarthritic chondrocytes and nucleus pulposus cells, respectively, the authors realize that their submission to International Journal of Molecular Medicine was in breach of the requirement that a submitted paper should represent an (entirely) original study presenting novel work, and that none of the data therein had been previously submitted to or accepted by any other journal. Therefore, following the advice of the Editor, they are going to retract the paper from International Journal of Molecular Medicine. All the named authors agree to this retraction. They sincerely apologize for this mistake, thank the reader of their article who drew this matter to their attention, and regret any inconvenience this has caused. [the original article was published in International Journal of Molecular Medicine Med 40: 845-853, 2017; DOI: 10.3892/ijmm.2017.3075].

12.
Medicine (Baltimore) ; 97(31): e11620, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075538

RESUMO

RATIONALE: Subacute combined degeneration (SCD) of the spinal cord has been reported to have distinctive characteristics on magnetic resonance imaging (MRI), such as an "inverted V sign", a "pair of binoculars sign", and a "dot sign". We report a 3-point sign as a novel MRI characteristic, expanding the spectrum of imaging signs for SCD. PATIENT CONCERNS: A 64-year-old female vegetarian presented with a 3-month history of progressive numbness and weakness in the lower extremities. DIAGNOSIS: Laboratory examination showed a reduced serum vitamin B12 level. Spinal MRI showed hyperintensity within the posterior and lateral columns (appearing as a three-point sign) on T2-weighted imaging. Thus, the patient was diagnosed with SCD. INTERVENTIONS: The patient was treated with intravenous cyanocobalamin and oral vitamin B12. OUTCOMES: After a follow-up period of 5 months, the symptoms were significantly improved. LESSONS: Clinicians should be aware of this atypical MRI pattern, which may facilitate an early diagnosis.


Assuntos
Imageamento por Ressonância Magnética , Medula Espinal/diagnóstico por imagem , Degeneração Combinada Subaguda/diagnóstico por imagem , Diagnóstico Precoce , Feminino , Humanos , Pessoa de Meia-Idade
13.
Medicine (Baltimore) ; 97(30): e11661, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30045319

RESUMO

RATIONALE: We report a rare case of syphilitic meningomyelitis presenting with visceral crisis and possessing characteristic imaging findings. PATIENT CONCERNS: The patient, a 50-year-old woman, complained of pain in the upper abdomen and back. She then developed numbness in both lower extremities and weakness in the left lower limb. DIAGNOSIS: Magnetic resonance imaging (MRI) of the spinal cord revealed the candle guttering sign and irregular enhancement at the T6 level. Rapid plasma reagin test of the cerebrospinal fluid yielded a titer of 1:8. Thus, the patient was diagnosed with syphilitic meningomyelitis. INTERVENTIONS: She was treated with ceftriaxone and dexamethasone after the failure of penicillin treatment. OUTCOMES: She could perform the activities of daily living, and her pain completely disappeared. LESSONS: A patient with syphilitic meningomyelitis can present with visceral crisis caused by the involvement of the posterior nerve roots or the posterior horn, which usually occurs in patients with tabes dorsalis. Considering the non-specific symptoms and MRI features, we should be aware that abdominal pain may be a symptom of myelopathy, and syphilitic meningomyelitis ought to be taken into account in a patient with longitudinally extensive myelitis.


Assuntos
Dor/etiologia , Estômago , Tabes Dorsal/diagnóstico , Dor Abdominal/etiologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dor nas Costas/etiologia , Ceftriaxona/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Hipestesia/etiologia , Extremidade Inferior , Pessoa de Meia-Idade , Tabes Dorsal/complicações , Tabes Dorsal/tratamento farmacológico
14.
Acc Chem Res ; 51(9): 2148-2158, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-29987929

RESUMO

Over the last two decades, interlocked molecular species have received considerable attention, not only because of their intriguing structures and topological importance, but also because of their potential applications as smart materials, nanoscale devices, and molecular machines. Through judicious choice of metal centers and their adjoining ligands, a range of interesting interlocked structures have been realized by coordination-driven self-assembly. In addition, researchers have extensively developed synthetic methodologies for the construction of organized self-assemblies. One fascinating and challenging synthetic target in this field is the family of molecular Borromean rings, which consist of three chemically independent rings that are locked in such a way that no two of the three rings are linked with each other. Toward this goal, we have developed a template-free self-assembly method for synthesizing molecular Borromean rings by rationally designing metal-containing precursors and organic ligands. In this Account, we present our recent work, focusing on interlocked structures comprising half-sandwich iridium- and rhodium-based organometallic assemblies obtained by rational design. We first describe a series of template-free self-assembled organometallic molecular Borromean rings, which we constructed from preorganized binuclear half-sandwich molecular clips and suitable pyridyl ligands. These molecular Borromean rings can be sorted into four types according to their different bridging ligands, including those based on metallaligands, dihalogenated ligands, naphthazarin and π-acceptor ligands. By single-crystal X-ray crystallographic analysis, NMR experiment, and DFT calculation, we discuss their driving forces and the inter-ring interactions. Furthermore, we took advantage of the dissimilarity in their interactions to realize selective, reversible conversions between molecular Borromean rings and monomeric rectangles by the use of suitable solvents or guest molecules. Subsequently, a stepwise chemoseparation method based on molecular Borromean rings was established, with the molecular Borromean rings used in the separation being recoverable and recyclable. Due to their structural complexity and difficult synthesis, useful guidelines or rules to help design complicated interlocked molecules are highly desirable. We also highlight our efforts to develop empirical guidelines to uncover the relationship between the aspect ratio of metallarectangles and the formation or stability of molecular Borromean rings. An empirical formula has further been established to show the approximate ratio of lengths of the short arm and the long arm in molecular Borromean rings based on π-π (or p-π) stacking. We then demonstrate how to use these guidelines to design new molecular Borromean rings and further lead to other interlocked structures, for example, [2]- and [3]catenane structures. Taken together, our results may lead to a promising future for the design of fascinating and useful interlocked structures by coordination-driven self-assembly.

15.
Biomed Res Int ; 2018: 5410875, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29651439

RESUMO

Wear debris induced aseptic loosening is the leading cause of total knee arthroplasty (TKA) failure. The complex mechanism of aseptic loosening has been a major issue for introducing effective prevention and treatment methods, so a simplified yet efficient rabbit model was established to address this concern with the use of micrometer-sized titanium particles. 20 New Zealand white rabbits were selected and divided into two groups (control = 10, study = 10). A TKA surgery was then performed for each of them, with implantation of a titanium rod prosthesis which was coated evenly with micrometer-sized titanium in the study group and nothing in the control group, into right femoral medullary cavity. After 12 weeks, all the animals were euthanized and X-ray analyses, H&E staining, Goldner Masson trichrome staining, Von Kossa staining, PCR, and Western blotting of some specific mRNAs and proteins in the interface membrane tissues around the prosthesis were carried out. The implantation of a titanium rod prosthesis coated with 20 µm titanium particles into the femoral medullary cavity of rabbits caused continuous titanium particle stimulation around the prosthesis, effectively inducing osteolysis and aseptic loosening. Titanium particle-induced macrophages produce multiple inflammatory factors able to activate osteoclast differentiation through the OPG/RANKL/RANK signaling pathway, resulting in osteolysis while suppressing the function of osteoblasts and reducing bone ingrowth around the prosthesis. This model simulated the implantation and loosening process of an artificial prosthesis, which is an ideal etiological model to study the aseptic prosthetic loosening.


Assuntos
Artroplastia do Joelho , Fêmur , Prótese do Joelho/efeitos adversos , Osteoclastos , Osteólise , Falha de Prótese/efeitos adversos , Titânio/efeitos adversos , Animais , Diferenciação Celular , Fêmur/metabolismo , Fêmur/patologia , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteólise/induzido quimicamente , Osteólise/metabolismo , Osteólise/patologia , Coelhos , Transdução de Sinais
16.
Chem Commun (Camb) ; 54(13): 1559-1562, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29300403

RESUMO

Template-free molecular Borromean rings (BRs) and open-ended molecular capsules were realized by strategic selection of the polypyridyl ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine (TPPHZ) with a large surface area and specific geometry. The topology of these intricate architectures was constructed via precisely controlled stacking interactions, as evidenced from single-crystal X-ray analysis.

17.
Exp Cell Res ; 358(2): 377-389, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28705727

RESUMO

The Piezo1 protein ion channel is a novel mechanical stretch-activated ion channel (SAC) closely related to mechanical signals. Mechanotransduction plays a crucial role in organ development and homeostasis. Previous studies identified Piezo1 and demonstrated that it is distinct from other ion channels with well-established roles in lower organisms. Mechanical stretch-activated ion channels from other organisms are not conserved in mammals or do not act as mechanically activated channels in mammals. In the current study, we explored the role of the Piezo1 ion channel in human nucleus pulposus cell (NP cell) apoptosis through mechanical force-induced mitochondrial dysfunction and endoplasmic reticulum stress. Reverse Transcription Polymerase chain reaction (RT-PCR), immunofluorescence, immunohistochemistry and Annexin V binding and propidium iodide analyses revealed that the Piezo1 protein ion channel was highly expressed in human NP cells, which are the primary cells that comprise the intervertebral disc. In patients with intervertebral disc degeneration (IVDD), the Piezo1 protein may play a crucial role in human NP cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress under abnormal loading conditions. This study also verified that human NP cells have an intimate connection with the cytoskeleton upon treatment of the cells with the Piezo1 blocking peptide GsMTx4 from tarantula venom. In summary, Piezo1 functions in human NP cell apoptosis, which may be one underlying mechanism of apoptosis induced by abnormal loading in IVDD patients.


Assuntos
Apoptose/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Canais Iônicos/metabolismo , Mecanotransdução Celular/fisiologia , Mitocôndrias/metabolismo , Núcleo Pulposo/metabolismo , Transdução de Sinais , Adulto , Feminino , Homeostase/fisiologia , Humanos , Disco Intervertebral/metabolismo , Transporte de Íons/fisiologia , Masculino , Pessoa de Meia-Idade
18.
Int J Mol Med ; 40(3): 845-853, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28731145

RESUMO

The present study was carried out to determine whether the mechanically activated cation channel Piezo1 protein plays a role as a signaling pathway which causes the apoptosis of human chondrocytes. The chondrocytes were isolated, cultured, and then subjected to mechanical stretch force for 0, 2, 12, 24 and 48 h, respectively. The expression levels of Piezo1 and the apoptosis-related protein caspase-12 were assessed by reverse transcription-quantitative polymerase chain reaction, as well as the apoptosis-related genes, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-associated X protein (Bax) and Bcl-2-associated death promoter (BAD). Lactate dehydrogenase (LDH) activity was used to discern dead cells. Piezo1 expression was determined by immunofluorescence. In addition, Piezo1 inhibitor, GsMTx4, was used to block the mechanically activated (MA) cation channel Piezo1, and served as a positive control. The results showed that the osteoarthritis (OA)-derived chondrocytes showed a tendency to undergo late-stage apoptosis under compressive loading. Piezo1 and caspase-12 were significantly upregulated under static compressive stimuli and the expression was related to the rate of apoptosis of the OA-derived chondrocytes during compressive loading. The expression of caspase-12 and late-stage apoptosis of the human OA-derived chondrocytes were repressed by GsMTx4, the specific inhibitor of Piezo1, while the expression of Piezo1 and the induction of the apoptosis of the OA-derived chondrocytes during compressive loading was not totally blocked. Thus, we conclude that Piezo1 plays an important role in the apoptosis of human OA-derived chondrocytes through a caspase-12-dependent pathway. The expression of Piezo1 protein was not totally inhibited by GsMTx4.


Assuntos
Apoptose , Condrócitos/metabolismo , Estresse do Retículo Endoplasmático , Canais Iônicos/metabolismo , Osteoartrite do Joelho/metabolismo , Transdução de Sinais , Adulto , Biomarcadores/metabolismo , Caspase 12 , Condrócitos/patologia , Ativação Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo
19.
Mol Med Rep ; 13(4): 3289-96, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26936538

RESUMO

The aim of the current study was to investigate the effects of Astragaloside­IV (AS­IV) on inflammatory mediators in synoviocytes and collagen­induced arthritic rats. Synoviocytes were stimulated with lipopolysaccharides (LPS) and Sprague­Dawley rats were injected with type II collagen. AS­IV was administered to the LPS­stimulated synoviocytes and collagen­induced arthritis (CIA) rats. The inflammation of LPS­stimulated synoviocytes and CIA rats was assessed using enzyme­linked immunosorbent assays and western blotting. Using Cell Counting Kit­8 analysis, it was demonstrated that AS­IV (5, 20 and 50 mg/ml) inhibited the LPS­stimulated synoviocytes proliferation in a dose­dependent manner. AS­IV significantly inhibited the LPS­stimulated inflammatory response, as indicated by the expression levels of TNF­α, IL­1ß, IL­6 and IL­8. In addition, treatment with AS­IV significantly reduced the LPS­stimulated cyclooxygenase (COX)­1, COX­2, high mobility group box 1 protein (HMGB1) and intercellular adhesion molecule 1 overexpression, and intranuclear nuclear factor (NF)­κBp65 subunit accumulation and activation of c­Jun N­terminal kinase (JNK)1/2 and p38. Similar to the protective effects of AS­IV on LPS­stimulated synoviocytes, AS­IV treatment significantly reduced the expression levels of tumor necrosis factor α, interleukin (IL)­1ß, IL­6 and IL­8 expression levels, and attenuated intranuclear NF­κBp65 subunit accumulation and overexpression of COX­2 and inducible nitric oxide synthase in CIA rats. In conclusion, the results of the present study demonstrated for the first time, to the best of our knowledge, that AS­IV protects synoviocytes against LPS­ and collagen­induced inflammatory responses through inhibition of the HMGB1­dependent JNK1/2­ and p38­activated NF­κB/COX­2 pathway.


Assuntos
Colágeno Tipo II/farmacologia , Mediadores da Inflamação/metabolismo , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Artrite Experimental/etiologia , Artrite Experimental/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Citocinas/análise , Regulação para Baixo/efeitos dos fármacos , Proteína HMGB1/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Saponinas/química , Sinoviócitos/citologia , Sinoviócitos/metabolismo , Triterpenos/química
20.
Saudi Med J ; 35(5): 435-41, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24825802

RESUMO

OBJECTIVE: To observe the effect of transfecting the gene human insulin-like growth factor (hIGF)-1 into human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) via non-viral vector. METHODS: This study was performed in the Affiliated Hospital of Qingdao University, Qingdao, China from June 2012 to May 2013. Twelve hUCB samples were harvested, and isolated in lymphocyte separation medium, and then cultured. Surface antigen expression in MSCs was detected by flow cytometry. Recombinant plasmid pIRES2-enhanced green fluorescent protein (EGFP)-hIGF-1 was transfected into MSCs by X-treme GENE HP DNA transfection reagent. Then, EGFP was observed with reverse fluorescent microscope at different time points. Enzyme-linked immunosorbent assay was used to determine the hIGF-1 protein concentration in supernatants. Immunofluorescence microscopy and reverse transcription polymerase chain reaction were used to detect the expression of hIGF-1 in the hUCB-MSCs. Expression of type II collagen was detected by immunohistochemistry staining. RESULTS: Transfection efficiency was 28.74 +/- 7.31%. The cluster of differentiation (CD)90, CD105, and CD146 expression increased CD34, CD45, and anti-HLA-DR expression decreased. Results of immunofluorescence microscopy and RT-PCR confirmed expression of the hIGF-1 gene. The hIGF-1 protein concentration in the supernatants showed a peak level at 34.63 +/- 1.61 ng/ml 48 hours after transfection. Immunohistochemical analysis of transfected hUCB-MSCs proved that type II collagen could be expressed positively. CONCLUSION: Human IGF-1 gene can be transfected into hUCB-MSCs, and expressed at a high level with subsequent expression of type II collagen.


Assuntos
Fator de Crescimento Insulin-Like I/genética , Células-Tronco Mesenquimais/metabolismo , Transfecção , Cordão Umbilical/metabolismo , Sequência de Bases , Primers do DNA , Humanos , Cordão Umbilical/citologia
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