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1.
Pharmacogenomics J ; 24(2): 5, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378770

RESUMO

OBJECTIVE: To explore the role of p300 in the context of paclitaxel (PTX) resistance in triple-negative breast cancer (TNBC) cells, focusing on its interaction with the phosphoenolpyruvate carboxykinase 1 (PCK1)/adenosine monophosphate-activated protein kinase (AMPK) pathway. METHODS: The expression of p300 and PCK1 at the messenger ribonucleic acid (mRNA) level was detected using a quantitative polymerase chain reaction. The GeneCards and GEPIA databases were used to investigate the relationship between p300 and PCK1. The MDA-MB-231/PTX cell line, known for its PTX resistance, was chosen to understand the specific role of p300 in such cells. The Lipofectamine™ 3000 reagent was used to transfer the p300 small interfering RNA and the overexpression of PCK1 plasmid into MDA-MB-231/PTX. The expression levels of p300, PCK1, 5'AMPK and phosphorylated AMPK (p-AMPK) were determined using the western blot test. RESULTS: In TNBC cancer tissue, the expression of p300 was increased compared with TNBC paracancerous tissue (P < 0.05). In the MDA-MB-231 cell line of TNBC, the expression of p300 was lower than in the PTX-resistant TNBC cells (MDA-MB-231/PTX) (P < 0.05). The PCK1 expression was decreased in the TNBC cancer tissue compared with TNBC paracancerous tissue, and the PCK1 expression was reduced in MDA-MB-231/PTX than in MDA-MB-231 (P < 0.05) indicating that PCK1 was involved in the resistance function. Additionally, p-AMPK was decreased in MDA-MB-231/PTX compared with MDA-MB-231 (P < 0.05). The adenosine triphosphate (ATP) level was also detected and was significantly lower in MDA-MB-231/PTX than in MDA-MB-231 (P < 0.05). Additionally, cell proliferation increased significantly in MDA-MB-231/PTX at 48 and 72 h (P < 0.05) suggesting that MDA-MB-231/PTX cells obtained the resistance function which was associated with AMPK and ATP level. When p300 was inhibited, p-AMPK and ATP levels elevated in MDA-MB-231/PTX (P < 0.05). When PCK1 was suppressed, the ATP consumption rate decreased, and cell proliferation increased (P < 0.05). However, there were no changes in p300. CONCLUSIONS: In MDA-MB-231/PTX, p300 can inhibit p-AMPK and ATP levels by inhibiting PCK1 expression. Our findings suggest that targeting p300 could modulate the PCK1/AMPK axis, offering a potential therapeutic avenue for overcoming PTX resistance in TNBC.


Assuntos
Paclitaxel , Neoplasias de Mama Triplo Negativas , Humanos , Trifosfato de Adenosina/uso terapêutico , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Peptídeos e Proteínas de Sinalização Intracelular/genética , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Regulação para Cima
2.
J Recept Signal Transduct Res ; 40(6): 584-590, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32456526

RESUMO

Osteosarcoma (OS) is the most frequent primary malignancy initially in bone with multiple genomic aberrations. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is linked with the progression of diverse tumors. However, its function in OS is not understood completely. The expression pattern and prognostic significance of MTHFD1L in OS tissues were analyzed based on GEO database. The expression level of MTHFD1L in OS cell lines was explored by qRT-PCR. The cell proliferation, colony formation ability, invasion as well as migration in OS cells after MTHFD1L knockdown were determined using cell counting kit 8 (CCK-8) assay, colony formation and transwell methods. GSEA analysis was performed to predict the underlying mechanisms of MTHFD1L in OS development. Furthermore, the western blot was utilized to study the influence of MTHFD1L on AKT/mTOR pathway. Our results indicated that MTHFD1L expression was significantly up-regulated in OS tissues and cells compared with normal tissues and cells. High expression of MTHFD1L could lead to poor prognosis of OS patients. Cell proliferation, colony formation ability, migration and invasion were blocked because of reduced MTHFD1L in vitro. Moreover, cell cycle and AKT/mTOR pathway were all associated with MTHFD1L expression. In conclusion, the findings revealed that MTHFD1L might promote the development of OS via mediating cell cycle and AKT/mTOR pathway, indicating that MTHFD1L might act as a promising therapeutic target for OS treatment.


Assuntos
Aminoidrolases/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Formiato-Tetra-Hidrofolato Ligase/metabolismo , Regulação Neoplásica da Expressão Gênica , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Complexos Multienzimáticos/metabolismo , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Aminoidrolases/genética , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Ciclo Celular , Movimento Celular , Proliferação de Células , Ácido Fólico/metabolismo , Formiato-Tetra-Hidrofolato Ligase/genética , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Complexos Multienzimáticos/genética , Invasividade Neoplásica , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/genética , Células Tumorais Cultivadas
3.
Eur Spine J ; 29(8): 2105, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32577863

RESUMO

Zhao-he and Sun-qingling are the co-first authors for this manuscript in the initial submission. Because of author's negligence and fault, this information was not shown clearly in the originally published article.

4.
Eur Spine J ; 28(5): 1092-1112, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30666481

RESUMO

PURPOSE: It is an open question whether cell transplantation can provide safety and effective outcome to spinal cord injury (SCI) patient which has remained controversial for almost 40 years. This study aimed to evaluate the safety and efficacy of cell transplantation in SCI patients. METHOD: Studies of the cell transplantation for SCI were retrieved from PubMed, Embase, Medline, Cochrane Library and analyzed quantitative data by Review Manager 5.3. RESULTS: Twenty-one clinical controlled studies with 973 patients were included. The pooled results suggested that cell transplantation significantly improved ASIA score, ASIA motor score, ASIA sensory score, Barthel Index score, residual urine volume, rehabilitative time of automatic micturition. Furthermore, subgroup analysis indicated that the stem cells exhibited more potent than the non-stem cells in spinal cord repair. Cell transplantation at more than 14 days after injury showed more significant improvements than that within 14 days from injury. The dosage of cell transplantation between 1-5 × 107 and 10-20 × 107 was the potent quantity for the patient with SCI. Intrathecal injection and intravenous + intrathecal injection showed more superior to the other method. The top 5 adverse events were febrile reaction (11.5%), neurologic pain (11.3%), headache (2.6%), neurologic deterioration (2.4%), and rigidity or spasticity (1.6%). CONCLUSION: Cell transplantation appears to be a safe therapeutic strategy possessing substantial beneficial effects in the patients with SCI in clinic. Moreover, treating SCI with stem cell, the dosage of cells between 1-5 × 107 and 10-20 × 107, in intermediate or chronic phase, minimally invasive techniques, may bring more advantage to SCI patient. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Transplante de Células , Traumatismos da Medula Espinal/cirurgia , Transplante de Células/efeitos adversos , Transplante de Células/métodos , Transplante de Células/estatística & dados numéricos , Humanos , Complicações Pós-Operatórias
5.
Artigo em Inglês | MEDLINE | ID: mdl-28674050

RESUMO

Thirty-nine fosfomycin-resistant Escherichia coli isolates carrying fosA3 were obtained from pigs, chickens, dairy cows, and staff in four northeastern provinces of China between June 2015 and April 2016. The fosA3 gene was colocated with blaCTX-M genes on conjugative plasmids of the incompatibility groups IncN (n = 12), IncN-F33:A-:B-(n = 2), IncF33:A-:B-(n = 14), IncF14:A-:B-(n = 2), and IncI1/sequence type 136 (ST136) (n = 9). Four different genetic contexts of fosA3 were detected among the 39 E. coli isolates. Three potential epidemic plasmids circulated among E. coli strains from this region.


Assuntos
Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Fosfomicina/farmacologia , Plasmídeos/genética , Animais , Bovinos , Galinhas/microbiologia , China , Infecções por Escherichia coli/microbiologia , Testes de Sensibilidade Microbiana/métodos , Suínos/microbiologia
6.
J Mater Sci Mater Med ; 28(1): 2, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27866345

RESUMO

Rib segment, as one of the most widely used autologous boneresources for bone repair, is commonly isolated with an empty left in the defect. Although defective rib repair is thought to be unnecessary traditionally, it's of vital importance actually to promote rib regeneration for patients with better postoperative recovery and higher life quality. Comparative investigations on rabbit rib bone regeneration with and without graft were reported in this article. A segmental defect was performed on the 8th rib of 4-month-old male New Zealand rabbits. The mineralized collagen bone graft (MC) was implanted into the defect and evaluated for up to 12 weeks. The rib bone repair was investigated by using X-ray at 4, 8 and 12 weeks and histological examinations at 12 weeks after surgery, which showed a higher bone remodeling activity in the groups with MC implantation in comparison with blank control group, especially at the early stage of remodeling.


Assuntos
Regeneração Óssea , Transplante Ósseo/métodos , Costelas/cirurgia , Animais , Remodelação Óssea , Substitutos Ósseos , Calcificação Fisiológica , Colágeno , Masculino , Coelhos , Costelas/lesões , Alicerces Teciduais , Cicatrização
7.
J Craniofac Surg ; 27(7): 1815-1818, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27564074

RESUMO

PURPOSE: The purpose of this study was to present the outcome and discuss the feasibility of rib composite flap with intercostal nerve and internal thoracic vessels for reconstructing mandibular defect. METHODS: Rib composite flaps have been used in 82 patients for reconstructing benign tumor-caused large mandibular defects: 66 of the 82 patients were reconstructed using rib composite flap with intercostal nerve and internal thoracic vessels, whereas the other 16 patients were reconstructed using rib composite flap with internal thoracic vessels, without intercostal nerve. After operation, clinical observation, imageological examination, and sensory detection were used to evaluate the effect of reconstruction. RESULTS: All rib composite flaps with intercostal nerve and internal thoracic vessels were successfully harvested and transplanted. Both immediate and long-term examination showed good appearance reconstruction. All followed-up patients conveyed good satisfaction degree with function and appearance reconstruction. Postoperative panoramic x-ray examination showed new bone formation between the transplanted rib and mandibular stump. Good recoveries of mandibular nerve sensory were observed when followed up after reconstruction surgery. CONCLUSIONS: Rib composite flap with intercostal nerve and internal thoracic vessels could be a promising method for reconstruction of mandibular defects.


Assuntos
Nervos Intercostais/cirurgia , Traumatismos Mandibulares/cirurgia , Reconstrução Mandibular/métodos , Costelas/transplante , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/inervação , Artérias Torácicas/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Antimicrob Agents Chemother ; 59(2): 1337-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25421479

RESUMO

Two porcine Escherichia coli isolates harbored the cfr gene on conjugative plasmids of 38,405 bp (pGXEC6) and 41,646 bp (pGXEC3). In these two plasmids, the cfr gene was located within a 4,612-bp region containing a tnpA-IS26-cfr-IS26-Δhyp element. Plasmid pGXEC3 was almost identical to pGXEC6 except for a 3,235-bp ISEcp1-blaCTX-M-14b insertion. The colocation of the multiresistance cfr gene with an extended-spectrum-ß-lactamase gene on a conjugative plasmid may support the dissemination of these genes by coselection.


Assuntos
Escherichia coli/enzimologia , beta-Lactamases/genética , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Plasmídeos/genética , Suínos
9.
Antimicrob Agents Chemother ; 59(11): 7113-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26324271

RESUMO

A novel nonconjugative plasmid of 28,489 bp from a porcine linezolid-resistant Enterococcus faecium isolate was completely sequenced. This plasmid harbored a novel type of multiresistance gene cluster that comprised the resistance genes lnu(B), lsa(E), spw, aadE, aphA3, and two copies of erm(B), which account for resistance to macrolides, lincosamides, streptogramins, pleuromutilins, streptomycin, spectinomycin, and kanamycin/neomycin. Structural comparisons suggested that this plasmid might have developed from other enterococcal plasmids by insertion element (IS)-mediated interplasmid recombination processes.


Assuntos
Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/genética , Animais , Antibacterianos/farmacologia , Diterpenos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Lincosamidas/farmacologia , Linezolida/farmacologia , Macrolídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Compostos Policíclicos , Estreptograminas/farmacologia , Suínos , Pleuromutilinas
10.
J Antimicrob Chemother ; 69(2): 385-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24013193

RESUMO

OBJECTIVES: To determine the complete nucleotide sequence of the multidrug resistance plasmid pSCEC2, isolated from a porcine Escherichia coli strain, and to analyse it with particular reference to the cfr gene region. METHODS: Plasmid pSCEC2 was purified from its E. coli J53 transconjugant and then sequenced using the 454 GS-FLX System. After draft assembly, predicted gaps were closed by PCR with subsequent sequencing of the amplicons. RESULTS: Plasmid pSCEC2 is 135 615 bp in size and contains 200 open reading frames for proteins of ≥100 amino acids. Analysis of the sequence of pSCEC2 revealed two resistance gene segments. The 4.4 kb cfr-containing segment is flanked by two IS256 elements in the same orientation, which are believed to be involved in the dissemination of the rRNA methylase gene cfr. The other segment harbours the resistance genes floR, tet(A)-tetR, strA/strB and sul2, which have previously been found on other IncA/C plasmids. Except for these two resistance gene regions, the pSCEC2 backbone displayed >99% nucleotide sequence identity to that of other IncA/C family plasmids isolated in France, Chile and the USA. CONCLUSIONS: The cfr gene was identified on an IncA/C plasmid, which is well known for its broad host range and transfer and maintenance properties. The location on such a plasmid will further accelerate the dissemination of cfr and co-located resistance genes among different Gram-negative bacteria. The genetic context of cfr on plasmid pSCEC2 underlines the complexity of cfr transfer events and confirms the role that insertion sequences play in the spread of cfr.


Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Metiltransferases/genética , Fosfoproteínas/genética , Plasmídeos/genética , Animais , Proteínas de Bactérias/isolamento & purificação , Elementos de DNA Transponíveis/genética , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Proteínas de Escherichia coli/isolamento & purificação , Metiltransferases/isolamento & purificação , Fosfoproteínas/isolamento & purificação , Suínos
11.
World J Gastrointest Oncol ; 16(4): 1465-1478, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660658

RESUMO

BACKGROUND: Colorectal cancer has a low 5-year survival rate and high mortality. Human ß-defensin-1 (hBD-1) may play an integral function in the innate immune system, contributing to the recognition and destruction of cancer cells. Long non-coding RNAs (lncRNAs) are involved in the process of cell differentiation and growth. AIM: To investigate the effect of hBD-1 on the mammalian target of rapamycin (mTOR) pathway and autophagy in human colon cancer SW620 cells. METHODS: CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration. Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation. Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway. Additionally, p-mTOR (Ser2448), Beclin1, and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis. RESULTS: hBD-1 inhibited the proliferative ability of SW620 cells, as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1. hBD-1 decreased the expression of p-mTOR (Ser2448) protein and increased the expression of Beclin1 and LC3II/I protein. Furthermore, bioinformatics analysis identified seven lncRNAs (2 upregulated and 5 downregulated) related to the mTOR pathway. The lncRNA TCONS_00014506 was ultimately selected. Following the inhibition of the lncRNA TCONS_00014506, exposure to hBD-1 inhibited p-mTOR (Ser2448) and promoted Beclin1 and LC3II/I protein expression. CONCLUSION: hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

12.
World J Gastrointest Surg ; 15(9): 1932-1940, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37901721

RESUMO

BACKGROUND: Perioperative nursing can reduce the stress reaction and improve the prognosis of children. AIM: To elucidate the influence of multidisciplinary collaborative nursing for enhanced recovery after surgery (ERAS) with family care in perioperative nursing children with an inguinal hernia and its impact on the prognosis. METHODS: The data of 100 children with inguinal hernia were retrospectively analyzed. The participants were divided into three groups according to different nursing methods: Groups A (n = 38), B (n = 32), and C (n = 30). Group A received multidisciplinary collaborative ERAS nursing combined with family care nursing; Group B received multidisciplinary collaborative nursing for ERAS; and Group C received routine nursing. The postoperative recovery results of the three groups were compared, including intraoperative blood loss and postoperative feeding time, time of getting out of bed, hospitalization time, and defecation time. Furthermore, the incidence of common complications was also compared between the three groups. RESULTS: There was less intraoperative blood loss in Groups A and B than in Group C (P < 0.05), and the time of getting out of bed and postoperative hospitalization and defecation times were also decreased in Group C (P < 0.05). There was no significant difference in postoperative feeding time among the three groups (P > 0.05). Each index had no statistical significance between Groups A and B (P > 0.05). The incidence of urinary retention, infection, hematoma, and hernia recurrence in Group A was less than that in Group C (P < 0.05). No significant difference was observed in the overall complication rate between Groups A and B and between Groups B and C (P > 0.05). CONCLUSION: The application of multidisciplinary collaborative nursing combined with family care in the perioperative care of children with an inguinal hernia for ERAS may promote postoperative rehabilitation for children and reduce the incidence of complications.

13.
Front Oncol ; 13: 1164331, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37350947

RESUMO

Hemangioma is a congenital vascular malformation that occurs commonly in the skin and soft tissues of younger individuals but rarely in the bone. The term hemangioma occurring in bone has been referred to as venous bony malformation also. In these rare cases, vertebral bodies occur more often, followed by the craniofacial skeleton and long bones. Most rib tumors are malignant, and hemangiomas of the rib tend to grow expansively and disrupt the cortex. Venous malformations in ribs are not tumors but can be misdiagnosed as aggressive tumors or infectious processes. In fact, hemangioma of bone is a locally aggressive benign vascular malformation associated with a good prognosis. To date, no more than 50 cases of rib hemangiomas have been described in the English literature. This report presents a case of an asymptomatic 27-year-old female patient who found a quail egg-sized lump on the right side of her chest that was the size of a cocoon 2 months prior. Then, the lump grew rapidly to the size of an egg when she presented to the hospital. Because of its worrisome histomorphologic features and aggressive clinical radiologic findings, it was once misdiagnosed as a malignant tumor by most doctors. However, the pathological results after the operation confirmed rib hemangioma. Therefore, this case report aims to share this particular case so that more doctors can better understand the particularity of this disease's progression.

14.
J Multidiscip Healthc ; 16: 3619-3628, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034876

RESUMO

Objective: To investigate the application of a multidisciplinary collaboration model to optimise the configuration management of orthopaedic external device sets in general hospitals. Methods: A pretest-post-test study design was used. Sixty patients who underwent unilateral total knee arthroplasty and 60 patients who underwent posterior lumbar interbody fusion between March and May 2022 were recruited as the control stage. Additionally, a total of 120 patients, 60 of each, who underwent the two procedures between September and November 2022, were recruited as the experimental stage. For the control stage, conventional external equipment management was used, and for the experimental stage, an external device management programme was implemented based on multidisciplinary collaboration with the control stage. Based on the PDSA cycle, the configuration management of orthopaedic external device sets was optimised, and the differences in collating and counting external devices, nurses' overtime in the external device stage and orthopaedic surgeon satisfaction were compared between the two stages. Results: Compared with the control stage, the collation count took less time (8.65 ± 0.25 min vs 5.37 ± 0.13 min; 13.55 ± 1.10 min vs 7.85 ± 0.82 min), the number of overtime hours was shorter (175.80 ± 12.19 min vs 96.68 ± 13.66 min) and orthopaedic surgeon satisfaction was improved (4.58 ± 0.62 vs 4.10 ± 0.68; 4.33 ± 0.73 vs 3.87 ± 0.77; 4.20 ± 0.71 vs 3.82 ± 0.71; 4.12 ± 0.69 vs 3.87 ± 0.72; 4.05 ± 0.68 vs 3.79 ± 0.68) in the experimental stage (all P < 0.05). Conclusion: Multidisciplinary collaboration offers various benefits for optimising the configuration of external device sets, such as reducing the time taken for the preoperative sorting and counting of external devices, enhancing nurses' work efficiency and improving surgeons' job satisfaction; therefore, it is worthy of reference in clinical practice.

15.
Cell Oncol (Dordr) ; 46(3): 777-791, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36920728

RESUMO

PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies worldwide, with dramatically increasing incidence and mortality for decades. However, current therapeutic strategies for CRC, including chemotherapies and immunotherapies, have only demonstrated limited efficacy. Here, we report a novel immune molecule, CD43, that can regulate the tumor immune microenvironment (TIME) and serves as a promising target for CRC immunotherapy. METHODS: The correlation of CD43 expression with CRC patient prognosis was revealed by public data analysis. CD43 knockout (KO) CRC cell lines were generated by CRISPR-Cas9 technology, and a syngenetic murine CRC model was established to investigate the in vivo function of CD43. The TIME was analyzed via immunohistochemical staining, flow cytometry and RNA-seq. Immune functions were investigated by depletion of immune subsets in vivo and T-cell functional assays in vitro, including T-cell priming, cytotoxicity, and chemotaxis experiments. RESULTS: In this study, we found that high expression of CD43 was correlated with poor survival of CRC patients and the limited infiltration of CD8+ T cells in human CRC tissues. Importantly, CD43 expressed on tumor cells, rather than host cells, promoted tumor progression in a syngeneic tumor model. Loss of CD43 facilitated the infiltration of immune cells and immunological memory in the TIME of CRC tumors. Mechanistically, the protumor effect of CD43 depends on T cells, thereby attenuating T-cell-mediated cytotoxicity and cDC1-mediated antigen-specific T-cell activation. Moreover, targeting CD43 synergistically improved PD-L1 blockade immunotherapy for CRC. CONCLUSION: Our findings revealed that targeting tumor-intrinsic CD43 could activate the antitumor immune response and provide particular value for optimized cancer immunotherapy by regulating the TIME in CRC patients.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Colorretais , Humanos , Animais , Camundongos , Imunoterapia , Neoplasias Colorretais/metabolismo , Ativação Linfocitária , Microambiente Tumoral
16.
Ibrain ; 9(2): 148-156, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37786547

RESUMO

In children after cardiac surgery, alterations in cognitive ability and behavior are increasingly common, but whether postoperative cognitive dysfunction (POCD) occurs in children undergoing noncardiac surgery is not known. The present study was performed to investigate the incidence rate and potential risk factors of early neurocognitive dysfunction in children after noncardiac surgery. Two hundred patients aged between 4 and 14 years old underwent elective noncardiac surgery and 100 healthy age-matched controls were enrolled in this prospective observational study. Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children-Revised were conducted 1 day before and 3 days after surgery. POCD was calculated and diagnosed as a combined Z score. Any factors that differed between POCD and non-POCD group (p < 0.10) were tested together by multivariate logistic regression analysis against the cognitive outcome of patients, to find out the independent risk factors of POCD. The general incidence of POCD was 15.6%. The univariate analysis revealed that POCD was associated with general anesthesia, surgical and anesthesia duration, early postoperative fever (EPF), and surgical history. However, only the history of surgery (p = 0.029), anesthesia duration (p = 0.010), and EPF (p < 0.001) were demonstrated to be independent risk factors for POCD. The occurrence rate of early POCD after noncardiac surgery in children is 15.6%. Children who had surgical history, longer anesthesia duration, or EPF are more prone to develop POCD.

17.
Zhonghua Yan Ke Za Zhi ; 48(1): 20-6, 2012 Jan.
Artigo em Zh | MEDLINE | ID: mdl-22490912

RESUMO

OBJECTIVES: To investigate the expression of matrix metalloproteinase-2 (MMP-2) and Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in rabbit corneas implanted with modified titanium skirt of keratoprosthesis in order to explore the potential roles. METHODS: A total of 20 New Zealand white rabbits with corneal alkali burn in right eye rabbit corneas were divided into three groups. There were 6 animals in each group. Skirt of hydroxyapatite/Sandblast-Titanium and Sandblast-Titanium were inserted into the corneal stroma of rabbits in group A and group B. The group C did not insert skirt as surgical control.2 rabbits were as normal control D group. A total of 20 New Zealand white rabbits were divided into four groups with the same way. The expression of MMP-2 and TIMP-2 was determined by immunohistochemistry at 1 month, 3 months. The expression of MMP-2 and TIMP-2 mRNA level was determined by real time-polymerase chain reaction, and its protein level was determined by western blot. The optical cylinder was implanted to rabbit corneas, which were implanted with modified titanium skirt after 3 months. RESULTS: There was one case of corneal dissolution being found in group F. MMP-2 and TIMP-2 immunoreactivities were expressed in the normal corneas, predominantly in the corneal epithelium. After injury, immunoreactivities of both MMP-2 and TIMP-2 were increased notably in the healing corneal epithelium, infiltrating inflammatory cells, stromal fibroblasts and in growing vascular endothelial cells. The expression of MMP-2 was lower in group A and E than that in group B and F after 1 month and 3 months (t = 12.05, 2.93, 12.006, 3.781, P < 0.05). The Western blot revealed no significant differences of MMP-2 mRNA between group 3 months and 2 weeks (t = 2.104, P > 0.05); MMP-2 immunoreactivities were absent or lowly expressed predominantly in the corneal epithelium of normal corneas. The expression of MMP-2, TIMP-2 mRNA level was parallel that of protein level. CONCLUSIONS: The expression of MMP-2 was lower in the corneal tissue sections of HA/SB-Ti skirt inserted eyes than that in the tissue sections of SB-Ti skirt inserted eyes. The studies of MMP-2, TIMP-2 can provide a new way to prevent the incidence of corneal dissolving after surgery for keratoprosthesis.


Assuntos
Córnea/metabolismo , Queimaduras Oculares/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Animais , Transplante de Córnea , Queimaduras Oculares/cirurgia , RNA Mensageiro/genética , Coelhos , Alicerces Teciduais , Titânio
18.
Zhongguo Zhen Jiu ; 42(7): 779-84, 2022 Jul 12.
Artigo em Zh | MEDLINE | ID: mdl-35793888

RESUMO

OBJECTIVE: To observe the effect of acupuncture and moxibustion on the water content of stratum corneum (WCSC), expression of serum inflammatory factors and aquaporin 3 (AQP3) in skin, lung and rectum in guinea pigs with eczema of skin damp-heat accumulation, and to explore the possible mechanism of acupuncture and moxibustion for regulating skin barrier function. METHODS: A total of 24 male albino guinea pigs were randomly divided into a blank group (n=6) and a modeling group (n=18). The guinea pigs in the modeling group were induced by 2,4-dinitrochlorobenzene (DNCB) to establish the eczema model of skin damp-heat accumulation. The guinea pigs with successful modeling were further randomly divided into a model group, a medication group and an acupuncture-moxibustion group, 6 guinea pigs in each group. The guinea pigs in the medication group were treated with loratadine tablets (0.8 mg/kg) by gavage, once a day for 7 days; the guinea pigs in the acupuncture-moxibustion group were treated with acupuncture at "Feishu" (BL 13), "Pishu" (BL 20), "Quchi" (LI 11), "Zusanli" (ST 36) and "Xuehai" (SP 10); at the same time, moxibustion was applied at "Feishu" (BL 13) and "Zusanli" (ST 36), moxibustion intervention for 10 min and needle retaining for 15 min at each acupoint, once a day for 7 days. The eczema area and severity index (EASI) score was evaluated before and After intervention, and WCSC and trans-epidermal water loss (TEWL) were measured by skin tester. After intervention, The HE staining was used to observe the changes of skin histomorphology in each group; ELISA was used to measure the contents of serum immunoglobulin E (IgE), interleukin (IL)-4 and IL-17; Western blot was used to measure the protein expression of AQP3 in skin, lung and rectum. RESULTS: Before the intervention, compared with the blank group, the EASI scores and TEWL were increased in the remaining groups (P<0.01), and the WCSC was decreased (P<0.01). After the intervention, compared with the model group, the EASI scores and TEWL were decreased (P<0.05, P<0.01), and WCSC was increased (P<0.01) in the medication group and the acupuncture-moxibustion group. The epidermal structure in the blank group was complete and the fibers in the dermis were arranged orderly; in the model group, epidermal hyperkeratosis, proliferation of granular layer, spinous cell layer and basal layer, and disordered arrangement of dermal fibers and infiltration of inflammatory cells were observed. The morphological performance in the medication group and the acupuncture-moxibustion group was better than that in the model group. Compared with the blank group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 and the protein expression of AQP3 in skin, lung and rectum were decreased in the model group (P<0.01, P<0.05). Compared with the model group, the contents of serum IgE and IL-17 were decreased and the contents of serum IL-4 were increased in the medication group and the acupuncture-moxibustion group (P<0.01), and the protein expression of AQP3 in skin, lung and rectum in the acupuncture- moxibustion group were increased (P<0.05). Compared with the medication group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 was decreased (P<0.01) in the acupuncture-moxibustion group. CONCLUSION: Acupuncture and moxibustion could improve the epidermal water metabolism and skin tissue morphology in guinea pigs with eczema of skin damp-heat accumulation. Its mechanism may be related to regulating inflammatory factors, up-regulating the expression of AQP3, and then repairing the skin barrier function.


Assuntos
Terapia por Acupuntura , Eczema , Moxibustão , Eczema/terapia , Temperatura Alta , Humanos , Imunoglobulina E , Interleucina-17 , Interleucina-4 , Masculino , Água
19.
J Korean Neurosurg Soc ; 65(2): 186-195, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35108774

RESUMO

OBJECTIVE: To explore the histological feature of the cervical disc degeneration in patients with degenerative ossification (DO) and its potential mechanisms. METHODS: A total of 96 surgical segments, from cervical disc degenerative disease patients with surgical treatment, were divided into ossification group (group O, n=46) and non-ossification group (group NO, n=50) based on preoperative radiological exams. Samples of disc tissues and osteophytes were harvested during the decompression operation. The hematoxylin-eosin staining, Masson trichrome staining and Safranin O-fast green staining were used to compare the histological differences between the two groups. And the distribution and content of transforming growth factor (TGF)-ß1, p-Smad2 and p-Smad3 between the two groups were compared by a semi-quantitative immunohistochemistry (IHC) method. RESULTS: For all the disc tissues, the content of disc cells and collagen fibers decreased gradually from the outer annulus fibrosus (OAF) to the central nucleus pulposus (NP). Compared with group NO, the number of disc cells in group O increased significantly. But for proteoglycan in the inner annulus fibrosus (IAF) and NP, the content in group O decreased significantly. IHC analysis showed that TGF-ß1, p-Smad2, and p-Smad3 were detected in all tissues. For group O, the content of TGF-ß1 in the OAF and NP was significantly higher than that in group NO. For p-Smad2 in IAF and p-Smad3 in OAF, the content in group O were significantly higher than group NO. CONCLUSION: Histologically, cervical disc degeneration in patients with DO is more severe than that without DO. Local higher content of TGF-ß1, p-Smad2, and p-Smad3 are involved in the disc degeneration with DO. Further studies with multi-approach analyses are needed to better understand the role of TGF-ß/Smads signaling pathway in the disc degeneration with DO.

20.
Front Surg ; 9: 809622, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923435

RESUMO

Objective: The present study explored the construction and application of a standardized postoperative pain-management procedure for patients with perianal abscess. Methods: Two study groups (the observation group and the intervention group) were established retrospectively. The observation group comprised 46 patients with perianal abscess who enrolled in this study between June 2019 and June 2020. The intervention group comprised 48 patients who enrolled in the study between July 2020 and July 2021. All patients were enrolled using the convenience sampling method. A pain-management team was established, and standardized procedure management was implemented in the intervention group, while routine pain management was implemented in the observation group. Indices related to the patients' postoperative pain-control satisfaction and rehabilitation were compared between the two groups. Results: The patients' pain-control satisfaction, wound edema score, edema disappearance time, urinary retention, and defecation difficulty following intervention were better in the intervention group than in the observation group, and the differences were statistically significant (P < 0.05 for all). Conclusion: The implementation of the standardized postoperative pain-management procedure in patients with perianal abscess can effectively improve the patient's level of pain and satisfaction and promote rehabilitation.

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