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2.
Cell Signal ; : 111237, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38810861

RESUMO

BACKGROUND: The study aimed to investigate the role of copper death-related genes (CRGs) in bladder cancer (BC) for improved prognosis assessment. METHODS: Multi-omics techniques were utilized to analyze CRG expression in BC tissues from TCGA and GEO databases. Consensus clustering categorized patients into molecular subtypes based on clinical characteristics and immune cell infiltration. RESULTS: An innovative risk assessment model identified eight critical genes associated with patient risk. In vitro and in vivo experiments validated LIPT1's significant impact on copper-induced cell death, proliferation, migration, and invasion in BC. CONCLUSION: This multi-omics analysis elucidates the pivotal role of CRGs in BC progression, suggesting enhanced risk assessment through molecular subtype categorization and identification of key genes like LIPT1. Insights into these mechanisms offer the potential for improved diagnosis and treatment strategies for BC patients.

3.
Int Immunopharmacol ; 132: 111780, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38603853

RESUMO

BACKGROUND: Glycopeptide antibiotic vancomycin is a bactericidal antibiotic available for the infection to Staphylococcus aureus (SA), however, SA has a strong adaptive capacity and thereby acquires resistance to vancomycin. This study aims to illuminate the possible molecular mechanism of vancomycin resistance of SA based on the 16S rRNA sequencing data and microarray profiling data. METHODS: 16S rRNA sequencing data of control samples and urinary tract infection samples were retrieved from the EMBL-EBI (European Molecular Biology Laboratory - European Bioinformatics Institute) database. Correlation of gut flora and clinical indicators was evaluated. The possible targets regulated by SA were predicted by microarray profiling and subjected to KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. CXCL10 gene knockout and overexpression were introduced to evaluate the effect of CXCL10 on the virulence of SA and the resistance to vancomycin. SA strains were co-cultured with urethral epithelial cells in vitro. The presence of SA virulence factors was detected using PCR. Biofilm formation of SA strains was assessed using the microtiter plate method. Furthermore, the antibiotic sensitivity of SA strains was evaluated through vancomycin testing. RESULTS: Gut flora and its species abundance had significant difference between urinary tract infection and control samples. SA was significantly differentially expressed in urinary tract infection samples. Resistance of SA to vancomycin mainly linked to the D-alanine metabolism pathway. SA may participate in the occurrence of urinary tract infection by upregulating CXCL10. In addition, CXCL10 mainly affected the SA resistance to vancomycin through the TLR signaling pathway. In vitro experimental results further confirmed that the overexpression of CXCL10 in SA increased SA virulence and decreased its susceptibility to vancomycin. In vitro experimental validation demonstrated that the knockout of CXCL10 in urethral epithelial cells enhanced the sensitivity of Staphylococcus aureus (SA) to vancomycin. CONCLUSION: SA upregulates the expression of CXCL10 in urethral epithelial cells, thereby activating the TLR signaling pathway and promoting resistance to glycopeptide antibiotics in SA.


Assuntos
Antibacterianos , Quimiocina CXCL10 , Infecções Estafilocócicas , Staphylococcus aureus , Infecções Urinárias , Resistência a Vancomicina , Vancomicina , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Vancomicina/farmacologia , Humanos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Resistência a Vancomicina/genética , Infecções Urinárias/microbiologia , Infecções Urinárias/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , RNA Ribossômico 16S/genética , Células Epiteliais/microbiologia , Células Epiteliais/efeitos dos fármacos , Feminino , Masculino
4.
Am J Transl Res ; 16(1): 255-271, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322576

RESUMO

OBJECTIVES: Heterotopic ossification (HO), whether hereditary or traumatic, refers to the abnormal formation of bone in extraskeletal sites, often triggered by inflammation or flare-ups. Unfortunately, there are currently no effective treatments for HO. Metformin is well-known for its anti-diabetic, anti-inflammatory, anti-aging, and anti-cancer effects. However, its potential role in treating HO remains uncertain. METHODS: Metformin was dissolved into water and given to mice. All the mice in this study were examined by microCT and myeloid cell quantification using flow cytometry. Complex activity kit was used to examine the activity of mitochondrial complexes of myeloid cells. RESULTS: In this study, we discovered that metformin effectively inhibits genetic and traumatic HO formation and progression. Additionally, we observed a significant increase in myeloid cells in the genetic and traumatic HO mouse model compared to uninjured mice. Notably, metformin specifically reduced the infiltration of myeloid cells into the injured sites of the genetic and traumatic HO model mice. Further investigations revealed that metformin targets mitochondrial complex I and suppresses mitochondrial metabolism in myeloid cells. CONCLUSION: These findings suggest that metformin suppresses HO development by potentially downregulating the mitochondrial metabolism of myeloid cells, offering a promising therapeutic option for HO treatment.

5.
Int Microbiol ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37987892

RESUMO

We determined whether there exists a complementary pathway of cordycepin biosynthesis in wild-type Cordyceps militaris, high-cordycepin-producing strain C. militaris GYS60, and low-cordycepin-producing strain C. militaris GYS80. Differentially expressed genes were identified from the transcriptomes of the three strains. Compared with C. militaris, in GYS60 and GYS80, we identified 145 and 470 upregulated and 96 and 594 downregulated genes. Compared with GYS80, in GYS60, we identified 306 upregulated and 207 downregulated genes. Gene Ontology analysis revealed that upregulated genes were mostly involved in detoxification, antioxidant, and molecular transducer in GYS60. By Clusters of Orthologous Groups of Proteins and Kyoto Encyclopedia of Genes and Genomes analyses, eight genes were significantly upregulated: five genes related to purine metabolism, one to ATP production, one to secondary metabolite transport, and one to RNA degradation. In GYS60, cordycepin was significantly increased by upregulation of ATP production, which promoted 3',5'-cyclic AMP production. Cyclic AMP accelerated 3'-AMP accumulation, and cordycepin continued to be synthesized and exported. We verified the novel complementary pathway by adding the precursor adenosine and analyzing the expression of four key genes involved in the main pathway of cordycepin biosynthesis. Adenosine addition increased cordycepin production by 51.2% and 10.1%, respectively, in C. militaris and GYS60. Four genes in the main pathway in GYS60 were not upregulated.

6.
Int Wound J ; 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878524

RESUMO

It is difficult to avoid deep surgical site infection after spinal surgery. Debridement combined with closed suction irrigation (CSI) and other treatment methods lead to greater trauma and lower satisfaction. We developed a new method for the treatment of SSI, which has the advantages of less invasiveness and lower cost. The cohort of this retrospective study comprised 26 patients with SSI after undergoing spinal surgery in our hospital from August 2017 to March 2022. The patients were divided into CSI and microtube drainage group according to treatment methods. The durations of antibiotic use and hospital stay, hospitalization costs, and functional scores during follow-up were compared between the two groups. The only baseline characteristic that differed between the two groups was sex. Infection was controlled in both groups and there were no recurrences during follow-up. However, the length of hospital stay after the first operation and the total length of stay were significantly greater in the CSI group. Hospitalization costs and antibiotic costs were significantly higher in the CSI group. Additionally, the duration of intravenous antibiotic use was significantly longer in the CSI group. Both the CSI and microtube drainage groups had significantly improved of Short Form Health Survey (SF-36) scores 6 months postoperatively. However, 3 months postoperatively, SF-36 scores were significantly lower in the CSI group. Compared with debridement followed by CSI, percutaneous micro-drainage tube irrigation combined with high negative pressure tube drainage is a more efficient and economical means of treating SSI after spinal surgery.

7.
Int J Spine Surg ; 17(3): 356-363, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37230800

RESUMO

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) may cause cervical myelopathy. In its multilevel form, it may not be easy to manage. Minimally invasive endoscopic posterior cervical decompression may be an alternative to traditional laminectomy surgery. METHODS: Thirteen patients with multilevel OPLL and symptomatic cervical myelopathy were treated with endoscopic spine surgery from January 2019 to June 2020. In this consecutive observational cohort study, pre- and postoperative Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI) were analyzed at a final follow-up of 2 years postoperatively. RESULTS: There were 13 patients consisting of 3 women and 10 men. The patient's average age was 51.15 years. At the final 2-year follow-up, the JOA score improved from a preoperative value of 10.85 ± 2.91 to 14.77 ± 2.13 postoperatively (P < 0.001). The corresponding NDI scores decreased from 26.61 ± 12.88 to 11.12 ± 10.85 (P < 0.001). There were no infections, wound complications, or reoperations. CONCLUSION: Direct posterior endoscopic decompression for multilevel OPLL is feasible in symptomatic patients when executed at a high skill level. While 2-year outcomes were encouraging and on par with historic data obtained with traditional laminectomy, future studies will need to show whether any long-term shortcomings exist.

10.
Sci Rep ; 13(1): 6231, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37069252

RESUMO

Ventriculoperitoneal shunt (VPS) placement is the standard procedure in the management of hydrocephalus. The introduction of laparoscopy allows better visualization during the operation and a more reliable placement of the peritoneal terminal of the catheter, which significantly decreases postoperative obstruction and malposition rates. However, the fixation methods of the peritoneal terminal of the catheter have not been previously discussed. The indications, techniques, and complications were compared between conventional VPS and laparoscopy-guided VPS. Furthermore, same analyses were performed within the laparoscopy-guided VPS group subdivided by three different techniques of the fixation of the peritoneal terminal of catheter, including suture and ligature, titanium clip fixation, and subcutaneous fixation. A total of 137 patients with hydrocephalus who received VPS treatment was retrospectively studied, 85 of which were laparoscopy-guided, and 52 were not. The distal ends of the catheters were all placed in the suprahepatic space. At least one year (mean 28.6 months) follow-up was given postoperatively. The average duration of the whole operation was 45 min for suture and ligature, 40 min for titanium clip fixation, and 30 min for the subcutaneous fixation, respectively. Six patients (4.4%) had obstructive of the ventricular catheter in total. The success rates for the laparoscopy-assisted VPS procedure and the conventional VPS procedure were 87.1% (74/85) and 80.8% (42/52), respectively. Within subgroups of the laparoscopy-assisted VPS divided by fixation methods, the procedures were successful in 85.2% (23/27) of suture and ligation, 82.1% (23/28) of titanium clip fixation, and 93.3% (28/30) of subcutaneous fixation, respectively. Two patients had dislocated shunt tube in peritoneal end in laparoscopy group, all in the titanium clip fixation subgroups. The laparoscopy-assisted VPS insertion is an ideal shunt method for its effectiveness and lesser complication rate after operation. The subcutaneous fixation method of the peritoneal terminal of catheter might be the optimal fixation technique.


Assuntos
Hidrocefalia , Laparoscopia , Humanos , Derivação Ventriculoperitoneal , Estudos Retrospectivos , Titânio , Laparoscopia/métodos , Hidrocefalia/cirurgia
11.
Int J Biol Macromol ; 233: 123502, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36736976

RESUMO

A new polysaccharide, named SP800201 with Mw of 2.17 × 105 g/mol, was isolated from Saposhnikoviae Radix. The monosaccharide composition of SP800201 mainly contained Gal, GalA, Ara, and Rha. SP800201 has a core structure containing GalA as the backbone and side chains consisting of GalA, Gal, Ara and Rha. Cell and zebrafish experiments were used to explore the immunomodulatory activity of SP800201. Results of vitro RAW264.7 cell experiments showed that SP800201 could significantly improve the proliferation and phagocytosis of macrophages, and promote the release of NO, TNF-α, IL-1ß, and IL-6. Results of vivo experiments in immunocompromised zebrafish showed that SP800201 could also significantly increase the density of immune cells, the number of macrophages, and reduce NO, TNF-α, IL-1ß, and IL-6. The above results showed that the Saposhnikoviae Radix polysaccharide has certain immunomodulatory activity.


Assuntos
Fator de Necrose Tumoral alfa , Peixe-Zebra , Animais , Camundongos , Interleucina-6 , Polissacarídeos/química , Macrófagos , Células RAW 264.7
12.
Front Oncol ; 12: 816760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033440

RESUMO

The BTN2/3 subfamilies are overexpressed in many cancers, including pan-glioma (low- and high-grade gliomas). However, the expression and prognosis of BTN2/3 subfamilies and tumor-infiltrating lymphocytes in pan-glioma remain unknown. In the present study, we systematically explored and validated the expression and prognostic value of BTN2/3 subfamily members in pan-glioma [The Cancer Genome Atlas-glioblastoma and low-grade glioma (TCGA-GBMLGG) merge cohort] using multiple public databases. We used clinical specimens for high-throughput verification and cell lines for qRT-PCR verification, which confirmed the expression profiles of BTN2/3 subfamilies. In addition, the function of the BTN2/3 subfamily members and the correlations between BTN2/3 subfamily expression and pan-glioma immune infiltration levels were investigated. We found that BTN2/3 subfamily members were rarely mutated. BTN2/3 subfamilies were overexpressed in pan-glioma; high expression of BTN2/3 subfamily members was correlated with poor prognosis. In addition, BTN2/3 subfamilies might positively regulate proliferation, and the overexpression of BTN2/3 subfamilies influenced cell cycle, differentiation, and glioma stemness. In terms of immune infiltrating levels, BTN2/3 subfamily expression was positively associated with CD4+ T-cell, B-cell, neutrophil, macrophage, and dendritic cell infiltrating levels. These findings suggest that BTN2/3 subfamily expression is correlated with prognosis and immune infiltration levels in glioma. Therefore, the BTN2/3 subfamilies can be used as biomarkers for pan-glioma and prognostic biomarkers for determining the prognosis and immune infiltration levels in pan-glioma.

14.
Front Surg ; 9: 885669, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684149

RESUMO

Objective: The study aims to explore the feasibility and clinical effect of posterior minimally invasive treatment of cruciate ligament tibial avulsion fracture. Methods: Posterior knee minimally invasive approach was used to treat avulsion fracture of posterior cruciate ligament (PCL) tibia in 15 males and 11 females. The length of the incision, intraoperative blood loss, operation time, postoperative hospital stay, residual relaxation, and fracture healing time were analyzed to evaluate the curative effect, learning curve, and advantages of the new technology. Neurovascular complications were recorded. During the postoperative follow-up, the International Knee Joint Documentation Committee (IKDC), Lysholm knee joint score, and knee joint range of motion were recorded to evaluate the function. Results: All 26 patients were followed up for 18-24 months, with an average of 24.42 ± 5.00 months. The incision length was 3-6 cm, with an average of 4.04 ± 0.82 cm. The intraoperative blood loss was about 45-60 ml, with an average of 48.85 ± 5.88 ml. The operation time was 39-64 min, with an average of 52.46 ± 7.64 min. The postoperative hospital stay was 2-5 days, with an average of 2.73 ± 0.87 days. All incisions healed grade I without neurovascular injury. All fractures healed well with an average healing time of 9.46 ± 1.33 weeks (range, 8-12 weeks). The Lysholm score of the affected knee was 89-98 (mean, 94.12 ± 2.49) at 12-month follow-up. The IKDC score was 87-95 with an average of 91.85 ± 2.19, and the knee range of motion was 129-148° with an average of 137.08 ± 5.59°. The residual relaxation was 1-3 mm, with an average of 1.46 ± 0.65 mm. Conclusion: This minimally invasive method provides sufficient exposure for internal fixation of PCL tibial avulsion fractures without the surgical complications associated with traditional open surgical methods. The process is safe, less invasive, and does not require a long learning curve.

15.
J Arthroplasty ; 36(9): 3148-3153, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33962823

RESUMO

BACKGROUND: To evaluate the influence of patellar morphology on knee joint function and patellofemoral tracking in patients with primary osteoarthritis after total knee arthroplasty (TKA) without patellar resurfacing. METHODS: We performed a retrospective study of 156 patients with primary osteoarthritis who underwent TKA without patellar resurfacing from April 2018 to July 2019. As per Wiberg classification, patients were divided into Wiberg type I (group A, n = 38), II (group B, n = 88), and III (group C, n = 30) groups. The clinical data, postoperative follow-up data, and radiological data between three groups were compared. RESULTS: There was no statistically significant difference in the HSS score and Feller score between the three groups before surgery and at each follow-up point after surgery (P > .05). At the last follow-up, there were no significant differences in the height and relative thickness of the patella between the three groups (P > .05). However, the incidence of anterior knee pain was significantly higher in group C than in the group B (P < .05). The patellar tilt angle was significantly larger in group C than in the groups A and B (both P < .05). The patellar facet angle was significantly larger in group A than in group B and C, which was also significantly larger in group B than in group C (both P < .05). CONCLUSION: Patients with three different morphologic types of the patella both exhibited improved knee joint function after TKA, however, patients with Wiberg type Ⅲ patella were more prone to have poor patellofemoral tracking and anterior knee pain after surgery.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Articulação Patelofemoral , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Patela/diagnóstico por imagem , Patela/cirurgia , Articulação Patelofemoral/diagnóstico por imagem , Articulação Patelofemoral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
16.
Cell Death Dis ; 12(6): 524, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021124

RESUMO

The molecule mechanisms of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in human diseases have been broadly studied recently, therefore, our research aimed to assess the effect of lncRNA taurine upregulated gene 1 (TUG1)/miR-187-3p/tescalcin (TESC) axis in pituitary adenoma (PA) by regulating the nuclear factor-kappa B (NF-κB) signaling pathway. We observed that TUG1 was upregulated in PA tissues and was associated with invasion, knosp grade and tumor size. TUG1 particularly bound to miR-187-3p. TUG1 knockdown inhibited cell proliferation, invasion, migration, and epithelial-mesenchymal transition, promoted apoptosis, and regulated the expression of NF-κB p65 and inhibitor of κB (IκB)-α in PA cells lines in vitro, and also inhibited tumor growth in vivo, and these effects were reversed by miR-187-3p reduction. Similarly, miR-187-3p elevation inhibited PA cell malignant behaviors and modulated the expression of NF-κB p65 and IκB-α in PA cells, and reduced in vivo tumor growth as well. TUG1 inhibition downregulated TESC, which was targeted by miR-187-3p. In conclusion, this study suggests that TUG1 sponges miR-187-3p to affect PA development by elevating TESC and regulating the NF-κB signaling pathway.


Assuntos
Adenoma/patologia , Proteínas de Ligação ao Cálcio/fisiologia , MicroRNAs/fisiologia , Neoplasias Hipofisárias/patologia , RNA Longo não Codificante/fisiologia , Adenoma/genética , Adenoma/metabolismo , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , Proliferação de Células/genética , Células Cultivadas , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Transdução de Sinais/genética , Adulto Jovem
17.
J Knee Surg ; 34(12): 1304-1309, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32330971

RESUMO

The study aimed to investigate the effects of postoperative position of knee on blood loss and functional recovery after total knee arthroplasty (TKA). We enrolled patients who underwent TKA from 2017 to 2019 in our department with osteoarthritis of the knee in this prospective and randomized study. The patients were randomly allocated to flexion or extension group. In the flexion group, the affected leg was elevated by 30 degrees at the hip and the knee was flexed by 30-degree, postoperatively, while in the extension group, the affected knee was fully extended postoperatively. Patients' data related to postoperative blood loss, Hospital for Special Surgery scores, pain intensity, usage of analgesic drugs, circumference of knee, and range of motion (ROM) of knee were recorded to assess the influence of postoperative leg position on clinical outcomes. Although the transfusion rate was similar between the two groups (p > 0.05), other parameters related to blood loss (including total blood loss, hidden blood loss, usage of analgesic drugs, and postoperative circumference of knee) were significantly lower in the flexion group than those in the extension group (p < 0.05). After 6 weeks and 6 months of rehabilitation, patients gained a similar ROM in the affected knee in both groups (p > 0.05). The length of hospital stay and medical expenses were similar in both groups. Incidence of wound infection and other complications was also similar in both groups (p > 0.05). Elevation of the hip by knee flexion of 30 degrees is an effective and simple method to reduce blood loss after TKA, and contributes to reduction of the dosage of analgesic drugs in the early postoperative period. The routine application of the present protocol also did not increase medical costs and length of hospital stay after TKA.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Posicionamento do Paciente , Estudos Prospectivos , Amplitude de Movimento Articular , Resultado do Tratamento
18.
Exp Mol Pathol ; 118: 104571, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33166495

RESUMO

BACKGROUND: RabGEF1 is a guanine-nucleotide exchange factor for RAB-5, which plays an oncogenic role in certain human cancers. However, the function of RabGEF1 in glioma has not been studied. Here, we report that the down-regulation of RabGEF1 inhibits the proliferation and metastasis, and induces autophagy of U251 glioblastoma cells. METHODS: The expression of RabGEF1 in glioma and normal tissues were measured by immunohistochemistry. Four siRNAs targeting different sites of RabGEF1 were conducted and the interference efficiencies were verified by qRT-PCR assay. Western blot was used to detect the expression of interest proteins. Cell proliferation was detected using CCK-8 and clone formation assay. Cell migration and invasion were analyzed by scratch assay and transwell assay, respectively. Flow cytometry was used to detect cell cycle distribution and apoptosis. RESULTS: RabGEF1 was significantly up-regulated in human glioma tissues. RabGEF1 knockdown reduced cell viability, induced cell cycle arrest and apoptosis in U251 cells. Cell migration and invasion were also inhibited when RabGEF1 silencing. Mechanism studies showed that Cyclin D1 and CDK4/6 were significantly down-regulated when RabGEF1 silencing. p53 and caspase mediated apoptotic pathway was activated by down-regulation of RabGEF1. Moreover, RabGEF1 knockdown also induced autophagy in glioma cells. The investigation of AKT and Erk pathways suggested that phosphorylated AKT, p70S6K and phosphorylated Erk were all decreased when RabGEF1 silencing. CONCLUSION: In conclusion, our data suggest that RabGEF1 is up-regulated in human glioma and down-regulation of RabGEF1 inhibited cell proliferation and metastasis, and induced autophagy of U251 glioblastoma cells, which might be mediated by inactivation of AKT and Erk signaling pathways.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Estudos de Casos e Controles , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Glioblastoma/genética , Glioblastoma/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Células Tumorais Cultivadas
19.
Cancer Manag Res ; 12: 8363-8377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982430

RESUMO

PURPOSE: DARS antisense RNA 1 (DARS-AS1) is a long non-coding RNA that has been validated as a critical regulator in several human cancer types. Our study aimed to determine the expression profile of DARS-AS1 in prostate cancer (PCa) tissues and cell lines. Functional experiments were conducted to explore the detailed roles of DARS-AS1 in regulating PCa carcinogenesis. Furthermore, the detailed mechanisms by which DARS-AS1 regulates the oncogenicity of PCa cells were uncovered. METHODS: Reverse transcription quantitative polymerase chain reaction was performed to analyze DARS-AS1 expression in PCa tissues and cell lines. Cell Counting Kit-8 assays, flow cytometry analyses, Transwell assays, and tumor xenograft experiments were conducted to determine the regulatory effects of DARS-AS1 knockdown on the malignant phenotype of PCa cells. Bioinformatics analysis was performed to identify putative microRNAs (miRNAs) targeting DARS-AS1, and the direct interaction between DARS-AS1 and miR-628-5p was verified using RNA immunoprecipitation and luciferase reporter assays. RESULTS: DARS-AS1 was highly expressed in PCa tissues and cell lines. In vitro functional experiments demonstrated that DARS-AS1 depletion suppressed PCa cell proliferation, promoted cell apoptosis, and restricted cell migration and invasion. In vivo studies revealed that the downregulation of DARS-AS1 inhibited PCa tumor growth in nude mice. Mechanistic investigation verified that DARS-AS1 functioned as an endogenous miR-628-5p sponge in PCa cells and consequently promoted the expression of metadherin (MTDH). Furthermore, the involvement of miR-628-5p/MTDH axis in DARS-AS1-mediated regulatory actions in PCa cells was verified using rescue experiments. CONCLUSION: DARS-AS1 functioned as a competing endogenous RNA in PCa by adsorbing miR-628-5p and thereby increasing the expression of MTDH, resulting in enhanced PCa progression. The identification of a novel DARS-AS1/miR-628-5p/MTDH regulatory network in PCa cells may offer a new theoretical basis for the development of promising therapeutic targets.

20.
PLoS One ; 15(9): e0239366, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991599

RESUMO

Platelet-derived growth factor-bb (PDGF-BB) is a potent chemokine and mitogen for fibroblasts, keratinocytes, and vascular endothelium in the injured area, believed to be effective in wound healing. However, the short half-life of PDGF-BB and its rapid release from the wound surface limited its efficacy in vivo and vitro. To evaluate the wound healing effects of dorsal skin in SD rats with polydopamine-assisted immobilized PDGF-BB on PLGA nanofibrous substrate. First, the effects of pDA-coating and PDGF-BB immobilization on the morphology, compositions, and hydrophilicity of substrates were evaluated in details. Second, the wound healing effect of pDA/PLGA/PDGF-BB substrate was assessed in the dorsal skin of SD rats. Last, the cytokine analysis by ELISA method was employed to evaluate the advantages of pDA/PLGA/PDGF-BB substrate on anti-inflammatory, angiogenesis, and cellular proliferation. This method significantly improved the immobilization amount and stability of PDGF-BB on the substrate (p<0.01), further improved the hydrophilicity of substrates (p<0.05). Furthermore, the wound closure process was much more accelerated in the pDA/PLGA/PDGF-BB group (p<0.05). H&E and CD31 staining informed that the wound treated by pDA/PLGA/PDGF-BB substrate showed a high degree of regeneration and angiogenesis. The cytokine analysis showed that pDA significantly reduced the high level of inflammatory cytokines such as TNF-α (p<0.05). And the immobilized PDGF-BB significantly elevated the level of TGF-ß and VEGF (p<0.05). The pDA/PLGA/PDGF-BB substrate showed great therapeutic effect on wound healing compared with other control groups via regulating anti-inflammatory, angiogenesis, and cellular proliferation. Absolutely, this report offered an available novel method for skin regeneration.


Assuntos
Becaplermina/química , Becaplermina/farmacologia , Citocinas/metabolismo , Indóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polímeros/química , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Proteínas Imobilizadas/química , Proteínas Imobilizadas/farmacologia , Cinética , Masculino , Ratos , Ratos Sprague-Dawley
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