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1.
Oncol Lett ; 28(3): 431, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39049985

RESUMO

Breast cancer has surpassed lung cancer as the most prevalent malignancy affecting women worldwide. Triple-negative breast cancer (TNBC) is the type of breast cancer with the worst prognosis. As a heterogeneous disease, TNBC has a pathogenesis that involves multiple oncogenic pathways, including involvement of gene mutations and alterations in signaling pathways. MicroRNAs (miRNAs) are small endogenous, single-stranded non-coding RNAs that bind to the 3' untranslated region of target cell mRNAs to negatively regulate the gene expression of these specific mRNAs. Therefore, miRNAs are involved in cell growth, development, division and differentiation stages. miRNAs are also involved in gene targeting in tumorigenesis, tumor growth and the regulation of metastasis, including in breast cancer. Meanwhile, miRNAs also regulate components of signaling pathways. In this review, the role of miRNAs in the TNBC signaling pathway discovered in recent years is described in detail. The new concept of bi-targeted therapy for breast cancer using miRNA and artificial intelligence is also discussed.

2.
BMC Musculoskelet Disord ; 25(1): 510, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961446

RESUMO

PURPOSE: Crowe IV developmental dysplasia of the hip (DDH) is a catastrophic hip disease. Moreover, obtaining ideal clinical efficacy in conventional total hip arthroplasty (THA) is often difficult. In this study, we aimed to assess the mid-term clinical results of THA with porous tantalum trabecular metal (TM) pads for acetabular reconstruction in the treatment of Crowe IV DDH. METHODS: A cohort of 28 patients (32 hips) diagnosed with Crowe type IV DDH who underwent acetabular reconstruction during THA using TM pads with scheduled follow-up between 2011 and 2018, were included in this study. Eight cases were men and 24 were women, with a mean age of 48.4 years (range, 36-72 years) and a mean follow-up was 74.3 months (range, 42-132 months). All patients underwent acetabular reconstruction using TM pads and total hip replacement with subtrochanteric osteotomy. RESULTS: At the final follow-up, 28 hips (87.5%) demonstrated mild or no postoperative limping. The Harris Hip Score improved from 58.4 ± 10.6 preoperatively to 85.6 ± 8.9. The mean pain, stiffness, and function scores on the Western Ontario and McMaster University Osteoarthritis index were 86.5 ± 10.2, 87.3 ± 12.4 and 85.4 ± 11.6 respectively. The mean score of patient satisfaction was 90.4 ± 7.6. Additionally, the SF-12 physical summary score was 41.8 ± 5.6 and the SF-12 mental summary score was 51.6 ± 5.4. TM construct survivorship due to all-cause failure was 90.6% at 5 years with 3 hips at risk, 87.5% at 10 years with 4 hips at risk. The survivorship due to failure from aseptic loosening was 96.9% at 5 years with 1hips at risk and 93.75% at 10 years with 2 hips at risk. CONCLUSION: This study demonstrated satisfactory mid-term clinical and radiological results with the application of TM pads for acetabular reconstruction combined with THA in patients with Crowe IV DDH. TRIAL REGISTRATION NUMBER: ChiCTR1800014526, Date: 18/01/2018.


Assuntos
Artroplastia de Quadril , Displasia do Desenvolvimento do Quadril , Prótese de Quadril , Tantálio , Humanos , Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , Adulto , Seguimentos , Displasia do Desenvolvimento do Quadril/cirurgia , Displasia do Desenvolvimento do Quadril/diagnóstico por imagem , Resultado do Tratamento , Acetábulo/cirurgia , Acetábulo/diagnóstico por imagem , Desenho de Prótese , Estudos Retrospectivos , Porosidade
3.
Artigo em Inglês | MEDLINE | ID: mdl-39010835

RESUMO

Hypoxia is a critical factor contributing to a poor prognosis and challenging glioma therapy. Previous studies have indicated that hypoxia drives M2 polarization of macrophages and promotes cancer progression in various solid tumors. However, the more complex and diverse mechanisms underlying this process remain to be elucidated. Here, we aimed to examine the functions of hypoxia in gliomas and preliminarily investigate the underlying mechanisms of M2 macrophage polarization caused by hypoxia. We found that hypoxia significantly enhances the malignant phenotypes of U87 and U251 cells by regulating glycolysis. In addition, hypoxia-mediated accumulation of the glycolysis product (lactic acid, LA), which is subsequently absorbed by macrophages to induce its M2 polarization, and this process is reverted by both the glycolysis inhibitor and silenced monocarboxylate transporter (MCT-1) in macrophages, indicating that M2 macrophages polarization is associated with the promotion of glycolysis by hypoxia. Interestingly, we also found that hypoxia-mediated LA accumulation in glioma cells upon uptake by macrophages upregulates H3K18La expression and promotes tumor necrosis factor superfamily member 9 (TNFSF9) expression in a histone-lactylation-dependent manner based on the results of ChIP-seq enrichment analysis. Subsequent in vitro and in vivo experiments further indicated that TNFSF9 facilitated glioma progression. Mechanistically, hypoxia-mediated LA accumulation in glioma cells is taken up by macrophages and then induces its M2 macrophage polarization by regulating TNFSF9 expression via MCT-1/H3K18La signaling, thus facilitating the malignant progression of gliomas.

4.
J Med Case Rep ; 18(1): 333, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39033155

RESUMO

BACKGROUND: Leiomyosarcoma is a tumor that can develop in any organ that contains smooth muscles. Although leiomyosarcoma is common, its epididymal localization is quite rare. CASE PRESENTATION: A 79-year-old male Chinese Han patient presented with mild pain in the right groin and scrotum for 3 years concomitant with right scrotal swelling. Ultrasonography and magnetic resonance imaging of the scrotum showed a irregular and heterogeneous mass that was extratesticular. Right high orchiectomy was performed, and pathological examination of the resected specimen confirmed the diagnosis of leiomyosarcoma of the epididymis with surgical margins clear of tumor. CONCLUSION: Epididymal leiomyosarcoma is rare and difficult to diagnose preoperatively. The final diagnosis of epididymal leiomyosarcoma requires histologic examination. Resection must be extensive and complete. The effect of chemotherapy and radiation on the epididymal leiomyosarcoma remains unclear. Recurrence is common, so follow-up is necessary.


Assuntos
Epididimo , Neoplasias dos Genitais Masculinos , Leiomiossarcoma , Orquiectomia , Humanos , Masculino , Leiomiossarcoma/patologia , Leiomiossarcoma/cirurgia , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/diagnóstico , Idoso , Epididimo/patologia , Epididimo/diagnóstico por imagem , Epididimo/cirurgia , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/cirurgia , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Neoplasias dos Genitais Masculinos/diagnóstico , Neoplasias dos Genitais Masculinos/terapia , Imageamento por Ressonância Magnética , Ultrassonografia
5.
Orthop Surg ; 16(8): 1912-1919, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38858808

RESUMO

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe orthopedic disease, which may cause severe hip dysfunction in later stage. Therefore, it is necessary to treat nontraumatic ONFH during the early stages. The aim of this study was to evaluate the clinical efficacy and survival rates of different combined therapies based on modified core decompression (CD) for early-stage nontraumatic ONFH. METHODS: This retrospective cohort study assessed 397 hips with ONFH who underwent different combined therapies based on modified CD in our institution between January 2010 and December 2017. Patients were classified into six groups based on treatment modalities, and were followed up at 1 year and 5 years postoperatively. Clinical outcomes, including Harris hip score (HHS) and Western Ontario and McMaster Universities osteoarthritis index (WOMAC), were compared to evaluate the hip function and quick rehabilitation effect. Radiographic progression of ONFH and the incidence of total hip arthroplasty were analyzed to evaluate the survival rate of ONFH postoperatively. Statistical analyses were mainly performed with Kruskal-Wallis test, chi-square test and Kaplan-Meier method. RESULTS: HHS increased significantly in all groups but showed no significant differences among the six groups in the first years. The nonvascularized allogeneic fibula with bone grafting (NVAF + BG) and percutaneous femoral neck-head fenestration with bone grafting via the direct anterior approach (DAA + BG) groups had significantly higher HHS (p = 0.010; p = 0.025) and WOMAC function score (p < 0.001; p = 0.012) than the CD group 5 years postoperatively. Compared with the CD group, all the other groups showed statistically significant differences in radiographic progression (p < 0.001) and a higher survival rate with no significant difference (p = 0.569). CONCLUSION: Our study demonstrates the potential use of NVAF + BG and DAA + BG, may serve as a promising combined therapy for the treatment of early-stage nontraumatic ONFH.


Assuntos
Transplante Ósseo , Descompressão Cirúrgica , Necrose da Cabeça do Fêmur , Humanos , Estudos Retrospectivos , Necrose da Cabeça do Fêmur/cirurgia , Masculino , Feminino , Descompressão Cirúrgica/métodos , Adulto , Pessoa de Meia-Idade , Terapia Combinada , Transplante Ósseo/métodos , Adulto Jovem , Artroplastia de Quadril/métodos
6.
Transl Cancer Res ; 13(2): 1139-1149, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482408

RESUMO

Background and Objective: Breast cancer is presently the most prevalent cancer and the leading cause of cancer-related deaths in women worldwide. Circular RNA (circRNA) is a class of closed circRNAs lacking a 5'-end cap structure and a 3'-end polyA tail, which is highly stable and widely involved in a variety of pathophysiological processes such as cell proliferation, differentiation, and apoptosis. In recent years, accumulating studies have shown that circRNAs play an important role in the development and prognosis of breast cancer, but there are fewer literature reviews on their intrinsic molecular mechanisms which is the aim of this study. Methods: This review synthesizes the findings of literature retrieved from searches of PubMed and Google Scholar databases, hand searches, and authoritative texts. Citations mainly originate from the past 3 years. The articles need to describe the role of circRNA in breast cancer; no language restrictions were imposed. Key Content and Findings: This review summarizes the latest relevant literature and systematically reviews the four main mechanisms of circRNA in breast cancer from the perspective of circRNA function. At the same time, we describe the formation mechanism, characterization, and biological functions of circRNAs. Conclusions: We reviewed the status of actual knowledge about circRNA biogenesis and functions and summarized novel findings regarding the molecular mechanism of circRNA in breast cancer. Meanwhile, this review explores the possibility of circRNAs for becoming new biodiagnostic indicators and therapeutic targets in breast cancer.

7.
J Mater Chem B ; 12(10): 2571-2586, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38363109

RESUMO

Management of diabetic wounds presents a global health challenge due to elevated levels of ROS in the wound microenvironment, persistent dysregulation of inflammation modulation, and limitations in commercially available dressings. Addressing this issue, we have developed a pH-responsive and glucose-sensitive multifunctional hydrogel dressing that dynamically responds to the wound microenvironment and enables on-demand drug release. The dressing incorporates a matrix material based on aminophenylboronic acid-functionalized alginate and a polyhydroxy polymer, alongside an enhancer phase consisting of self-assembled metal-phenol coordination nanospheres formed by tannic acid and iron ions. Using the dynamic borate ester bonds and catechol-metal ion coordination bonds, the dressing exhibits remarkable shape adaptability, self-healing capability, tissue adhesiveness, antioxidant activity, and photothermal responsiveness, without additional curatives or crosslinking agents. As a wound dressing, it elicits macrophage polarization towards an anti-inflammatory phenotype while maintaining long-lasting antimicrobial effects. In a diabetic mouse model of full-thickness wound infections, it effectively mitigated inflammation and vascular damage, significantly expediting the wound healing process with a commendable 97.7% wound closure rate. This work provides a new direction for developing multifunctional smart hydrogel dressings that can accelerate diabetic wound healing for human health.


Assuntos
Diabetes Mellitus , Nanosferas , Polifenóis , Humanos , Animais , Camundongos , Fenóis , Metais , Alginatos , Inflamação , Hidrogéis/farmacologia
8.
Adv Healthc Mater ; 12(31): e2301517, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37689990

RESUMO

Photodynamic therapy is a promising cancer therapeutic method that can damage DNA via photoinduced reactive oxygen species production. However, tumor cells can initiate DNA repair pathways to resist oxidative damage. In this study, a nuclear-targeted photosensitizer PARP-PS with a poly (ADP-ribose) polymerase 1 (PARP1) inhibitory effect is developed based on the reported PARP1 inhibitor, rucaparib. As a dual-mode DNA-damaging agent, PARP-PS damages DNA upon photoirradiation and enhances oxidative DNA damage by blocking the DNA repair pathway via PARP1 inhibition and degradation. Both in vitro and in vivo investigations demonstrate that PARP-PS exhibits high antitumor activity with few side effects in breast cancer. In addition, PARP-PS can act as an immunogenic cell death inducer to activate immune responses characterized by the promotion of cytotoxic T lymphocyte activation and tumor infiltration. Therefore, PARP-PS is a potential multimodal antitumor agent with synergistic phototherapeutic, chemotherapeutic, and immunotherapeutic effects.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Dano ao DNA , Neoplasias da Mama/tratamento farmacológico , DNA , Linhagem Celular Tumoral , Reparo do DNA , Poli(ADP-Ribose) Polimerase-1/genética
9.
Biologics ; 17: 113-128, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37767463

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is conventionally characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), accounting for approximately 15-20% of all breast cancers. Compared to other molecular phenotypes, TNBC is typically associated with high malignancy and poor prognosis. Cytotoxic agents have been the mainstay of treatment for the past few decades due to the lack of definitive targets and limited therapeutic interventions. However, recent developments have demonstrated that TNBC has peculiar molecular classifications and biomarkers, which provide the possibility of evolving treatment from basic cytotoxic chemotherapy to an expanding domain of targeted therapies. This review presents a framework for understanding the current clinical experience surrounding molecular biology mechanisms in TNBC (Figure 1). Including immunotherapy, polymerase (PARP) and PI3K/AKT pathway inhibitors, antibody-drug conjugates, and androgen receptor (AR) blockade. Additionally, the role of miRNA therapeutics targeting TNBC and potential strategies targeting cancer stem cells (CSCs) are discussed and highlighted. As more and more treatments arise on the horizon, we believe that patients with TNBC will have a new sense of hope.

10.
J Med Chem ; 66(15): 10265-10272, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37421416

RESUMO

In this work, we described a photocatalytic approach, termed ligand-directed photodegradation of interacting proteins (LDPIP), for efficient protein-protein heterodimer degradation. This LDPIP approach utilizes a combination of a photosensitizing protein ligand and appropriate light and molecular oxygen to induce oxidative damage to the ligand-binding protein as well as its interacting protein partner. As a showcase study, a photosensitizing HER2 ligand HER-PS-I was rationally designed based on the FDA-approved HER2 inhibitor lapatinib to efficiently degrade HER2 together with its interacting protein partner HER3, which is thought to induce HER2-targeted therapy resistance and difficult to target by small molecules. HER-PS-I exhibited excellent anticancer activity against drug-resistant MDA-MB-453 cells and its three-dimensional multicellular spheroids. We hope that this LDPIP approach would find more applications in degrading proteins that are thought undruggable or difficult to drug.


Assuntos
Antineoplásicos , Lapatinib/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Trastuzumab , Receptor ErbB-2/metabolismo , Ligantes , Fotólise , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Receptor ErbB-3/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos
11.
ACS Appl Mater Interfaces ; 15(24): 28891-28906, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37305922

RESUMO

Glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) is a serious bone disease that often affects young individuals. Bone grafting combined with core decompression is mainly used in the clinic to treat GC-ONFH. However, the outcome is usually not satisfactory, as expected. Here, we report an engineered exosome-functionalized extracellular matrix-mimicking hydrogel for promoting bone repair in GC-ONFH. Compared with Con-Exo, exosomes secreted by bone marrow stem cells (BMSCs) in conventional culture medium, the engineered Li-Exo, exosomes derived from bone marrow stem cells (BMSCs) stimulated by lithium ions, promoted macrophage M2 polarization while inhibiting macrophage M1 polarization. Furthermore, inspired by the fact that hydrogels can serve as desirable carriers of exosomes to facilitate their release in a sustained manner for improved therapeutic efficiency and in vivo application, an extracellular matrix (ECM)-mimicking hydrogel (Lightgel) composed of methacryloylated type I collagen was employed to incorporate Li-Exo/Con-Exo to construct the Lightgel-Li-Exo hydrogel/Lightgel-Con-Exo hydrogel. In vitro studies showed that the Lightgel-Li-Exo hydrogel had the most significant pro-osteogenic and pro-angiogenic activity. Finally, we evaluated the therapeutic effects of the hydrogel in rat models of GC-ONFH. As a result, the Lightgel-Li-Exo hydrogel had the most significant effect on enhancing macrophage M2 polarization, osteogenesis, and angiogenesis to promote bone repair in GC-ONFH. Taken together, this novel engineered exosome-functionalized ECM-mimicking hydrogel could be a promising strategy for osteonecrosis treatment.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Osteonecrose , Ratos , Animais , Glucocorticoides , Cabeça do Fêmur , Hidrogéis/farmacologia , Matriz Extracelular
12.
Neuroscience ; 526: 74-84, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37290685

RESUMO

Ischemic stroke is one of the main causes of serious disability and death worldwide. NLRP3 inflammasome is an intracellular pattern recognition receptor composed of polyprotein complex, which participates in mediating a series of inflammatory responses and is considered as a potential target for the treatment of ischemic stroke. Vinpocetine, a derivative of vincamine, has been widely used in the prevention and treatment of ischemic stroke. However, the therapeutic mechanism of vinpocetine is not clear, and its effect on NLRP3 inflammasome remains to be determined. In this study, we used the mouse model of transient middle cerebral artery occlusion (tMCAO) to simulate the occurrence of ischemic stroke. Different doses of vinpocetine (5, 10, 15 mg/kg/d) were injected intraperitoneally for 3 days after ischemia-reperfusion in mice. The effects of different doses of vinpocetine on the degree of ischemia-reperfusion injury in mice were observed by TTC staining and modified neurological severity score scale, and the optimal dose was determined. Then, based on this optimal dose, we observed the effects of vinpocetine on apoptosis, microglial proliferation and NLRP3 inflammasome. In addition, we compared the effects of vinpocetine and MCC950 (a specific inhibitor of NLRP3 inflammasome) on NLRP3 inflammasome. Our results show that vinpocetine can effectively reduce the infarct volume and promote the recovery of behavioral function in stroke mice, and the maximal beneficial effects were observed at the dose of 10 mg/kg/d. Vinpocetine can effectively inhibit the apoptosis of peri-infarct neurons, promote the expression of Bcl-2, inhibit the expression of Bax and Cleaved Caspase-3, and reduce the proliferation of peri-infarct microglia. In addition, vinpocetine, like MCC950, can reduce the expression of NLRP3 inflammasome. Therefore, vinpocetine can effectively alleviate the ischemia-reperfusion injury in mice, and the inhibition of NLRP3 inflammasome may be an important therapeutic mechanism of vinpocetine.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Sulfonamidas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais
13.
Eur J Med Chem ; 255: 115418, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37119664

RESUMO

Development of safe and effective photosensitizers is important for enhancing the efficacy of photodynamic cancer therapy. Phenalenone is a type II photosensitizer with a high singlet oxygen quantum yield; however, its short UV absorption wavelength hinders its application in cancer imaging and in vivo photodynamic therapy. In this study, we report a new redshift phenalenone derivative, 6-amino-5-iodo-1H-phenalen-1-one (SDU Red [SR]), as a lysosome-targeting photosensitizer for triple-negative breast cancer therapy. SDU Red produced singlet oxygen (Type II reactive oxygen species [ROS]) and superoxide anion radicals (Type I ROS) upon light irradiation. It also exhibited good photostability and a remarkable phototherapeutic index (PI > 76) against triple-negative breast cancer MDA-MB-231 cancer cells. Additionally, we designed two amide derivatives, SRE-I and SRE-II, with decreased fluorescence and photosensitizing capabilities based on SDU Red as activatable photosensitizers for photodynamic cancer therapy. SRE-I and SRE-II could be further converted into the active photosensitizer SDU Red via carboxylesterase-catalyzed amide bond cleavage. Moreover, SDU Red and SRE-II induced DNA damage and cell apoptosis in the presence of light. Therefore, SRE-II can act as a promising theranostic agent for triple-negative breast cancer.


Assuntos
Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio , Oxigênio Singlete/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fotoquimioterapia/métodos
14.
Protein J ; 42(4): 365-373, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36892742

RESUMO

Exosomes are responsible for cell-to-cell communication and serves as a valuable drug delivery vehicle. However, exosome heterogeneity, non-standardized isolation methods and proteomics/bioinformatics approaches limit its clinical applications. To better understand exosome heterogeneity, biological function and molecular mechanism of its biogenesis, secretion and uptake, techniques in proteomics or bioinformatics were applied to investigate human embryonic kidney cell (293T cell line)-derived exosome proteome and enable an integrative comparison of exosomal proteins and protein-protein interaction (PPI) networks of eleven exosome proteomes extracted from diverse human samples, including 293T (two datasets), dermal fibroblast, mesenchymal stem cell, thymic epithelial primary cell, breast cancer cell line (MDA-MB-231), patient neuroblastoma cell, plasma, saliva, serum and urine. Mapping of exosome biogenesis/secretion/uptake-related proteins onto exosome proteomes highlights exosomal origin-specific routes of exosome biogenesis/secretion/uptake and exosome-dependent intercellular communication. The finding provides insight into comparative exosome proteomes and its biogenesis, secretion and uptake, and potentially contributes to clinical applications.


Assuntos
Exossomos , Proteoma , Humanos , Proteoma/metabolismo , Linhagem Celular , Células Epiteliais/metabolismo
15.
Int J Biol Macromol ; 234: 123691, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36806769

RESUMO

A novel injectable hydrogel dressing (GA@AgNPs-SA) with long-term antimicrobial effect is developed that can accelerate the closure of bacteria-infected wounds. The hydrogel dressing was prepared by cross-linking sodium alginate molecular chains and gallic acid functionalized silver nanoparticles (GA@AgNPs) via calcium ions to form a three-dimensional network. The hydrogel dressing demonstrates excellent biocompatibility and can achieve a sustainable release of silver ions, ensuring a long-term antibacterial activity and inhibiting biofilm formation. Moreover, an in vivo study demonstrates that the GA@AgNPs-SA hydrogel can effectively decrease the expression of IL-6 and TNF-α to alleviate the inflammatory response, and promote angiogenesis by upregulating CD31, α-SMA and VEGF expression, thus significantly accelerating the repair of infected wounds. Given these interesting properties, this antibacterial hydrogel has great potential for application in the clinical care of bacteria-infected wounds.


Assuntos
Nanopartículas Metálicas , Cicatrização , Prata/farmacologia , Hidrogéis/farmacologia , Alginatos , Antibacterianos/farmacologia , Íons
17.
Adv Healthc Mater ; 11(1): e2101412, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34694067

RESUMO

Corticosteroids-induced Dickkopf-1 (DKK1) upregulation and Wnt signaling inhibition result in bone metabolism disorder and steroid-associated osteonecrosis (SAON). Implanting biomaterials to regulate the Wnt pathway is a promising method to repair challenging bone defects associated with SAON. Here, tetrahedral DNA nanostructures (TDNs) are fabricated as gene carriers to deliver MiR335-5p, which targets DKK1 translation. Heparin lithium hydrogel (Li-hep-gel) is synthesized to act as a lithium and MiR@TDNs delivery agent. Finally, the repair effects on challenging bone defect in SAON using a MiR@TDNs/Li-hep-gel composite are assessed in vivo. The results reveal that MiR@TDNs are absorbed by bone mesenchymal stem cells (BMSCs) and increase cell viability and reduce apoptosis. Moreover, MiR@TDNs promote alkaline phosphatase expression and calcium nodular deposition, decrease lipid droplet expression of BMSCs, and improve vascular endothelial growth factor secretion and vascular-like structure formation in vitro. After MiR@TDNs/Li-hep-gel is implanted into the SAON model, the internal bone defect of osteonecrosis is repaired with a large area of new bone accompanied with neovascularization and reduced empty lacunae. In conclusion, MiR@TDNs/Li-hep-gel can provide dual delivery of lithium and MiR@TDNs, which synergistically upregulate the Wnt signaling pathway, enhancing bone regeneration in challenging bone defects, and can be potentially used in SAON repair.


Assuntos
MicroRNAs , Nanoestruturas , Osteonecrose , DNA , Heparina , Humanos , Hidrogéis , Lítio , Osteogênese , Esteroides , Fator A de Crescimento do Endotélio Vascular
18.
J Orthop Surg Res ; 16(1): 591, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645496

RESUMO

BACKGROUND: Adductor canal block (ACB) with additional nerve blocks (ANBs) is reported to provide adequate analgesia and enhanced functional rehabilitation in total knee arthroplasty (TKA). The present study aims to evaluate whether ANBs are superior to multiple-site infiltration analgesia (MIA) in patients undergoing TKA under ACB. METHODS: We enrolled 530 patients undergoing primary TKA from 2015 to 2019 at our institution in this retrospective cohort study. Patients were divided into two groups: Group A was treated with ANBs + ACB; Group B was treated with MIA + ACB. Primary outcomes were pain scores and morphine consumption. Functional recovery was the secondary outcome. Other outcomes included satisfaction score, cost-effectiveness, adverse events, and length of hospital stay (LOS). RESULTS: Pain scores at rest and morphine consumption were slightly lower in the ANBs + ACB group than in the MIA + ACB group. No significant difference was found in functional recovery, post-operative complications or LOS between the groups. Meanwhile, the cost of analgesic intervention in the MIA + ACB group was less than that in the ANBs + ACB group. CONCLUSION: The present study suggests that ANBs do not provide superior pain relief compared to MIA for patients undergoing TKA under ACB. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100043227. Registered 9 February 2021, https://www.chictr.org.cn/showproj.aspx?proj=121745 .


Assuntos
Analgesia , Artroplastia do Joelho , Bloqueio Nervoso , Analgésicos Opioides , Anestésicos Locais , Artroplastia do Joelho/efeitos adversos , Humanos , Morfina , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Estudos Retrospectivos
19.
Biosci Rep ; 41(10)2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34612484

RESUMO

MicroRNAs (miRNAs) play important roles in a variety of human diseases, including breast cancer. A number of miRNAs are up- and down-regulated in breast cancer. However, little is known about miRNA similarity and similarity network in breast cancer. Here, a collection of 272 breast cancer-associated miRNA precursors (pre-miRNAs) were utilized to calculate similarities of sequences, target genes, pathways and functions and construct a combined similarity network. Well-characterized miRNAs and their similarity network were highlighted. Interestingly, miRNA sequence-dependent similarity networks were not identified in spite of sequence-target gene association. Similarity networks with minimum and maximum number of miRNAs originate from pathway and mature sequence, respectively. The breast cancer-associated miRNAs were divided into seven functional classes (classes I-VII) followed by disease enrichment analysis and novel miRNA-based disease similarities were found. The finding would provide insight into miRNA similarity, similarity network and disease heterogeneity in breast cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Redes Reguladoras de Genes , MicroRNAs/genética , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos
20.
Am J Transl Res ; 13(8): 9914-9917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540128

RESUMO

[This corrects the article on p. 6632 in vol. 11, PMID: 31737213.].

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