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1.
J Am Chem Soc ; 146(29): 19643-19648, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38990177

RESUMO

We report 9 crystal structures of a two-dimensional (2D) covalent organic framework (COF), including the parent Py-1P, 5 derivatives formed by chemical reactions, and 3 dynamic states by solvent exchange/loss. Structure details of these porous crystals, including stacking mode, interlayer distance, pore aperture, and incline angle, before, during, and after conversion processes in solution, were unveiled by single-crystal X-ray diffraction with resolutions up to 0.85 Å. The structure evolution is triggered by stepwise conformational transformation of the molecular building blocks in 2D COF, while their long-range ordering remained unsacrificed.

2.
Cancer Sci ; 113(9): 2962-2973, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35289035

RESUMO

The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathological development. Dysregulation of N6-methyladenosine (m6A) modification has begun to emerge as a significant contributor to cancer development and progression. However, the biological effects and molecular mechanisms of m6A modification in arecoline-promoted OSCC malignance remain elusive. We reveal that chronic arecoline exposure substantially induces upregulation of fat mass and obesity-associated protein (FTO), MYC, and programmed cell death-ligand 1 (PD-L1) in OSCC cells. Moreover, upregulation of PD-L1 is observed in OSCC cell lines and tissues and is associated with areca nut chewing in OSCC patients. We also demonstrate that arecoline-induced FTO promotes the stability and expression levels of PD-L1 transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells. Blockage of PD-L1 by administration of anti-PD-L1 antibody shrinks tumor size and improves mouse survival by elevating T-cell-mediated tumor cell killing. Therefore, targeting PD-L1 might be a potential therapeutic strategy for treating PD-L1-positive OSCC patients, especially those with habitual areca nut chewing.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Apoptose , Areca/efeitos adversos , Areca/metabolismo , Arecolina/farmacologia , Carcinoma de Células Escamosas/patologia , Imunidade , Ligantes , Camundongos , Neoplasias Bucais/patologia , Obesidade/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço
3.
Anticancer Drugs ; 33(1): e491-e499, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261923

RESUMO

The most common pathological subtype of renal carcinoma is RCC, and its development is closely related to immune infiltration. In our study, we investigated the relationship between zinc finger protein 668 and the prognostic risk, clinical characteristics, overall survival and related pathways. We analyzed the association between ZNF668 and immune cell infiltration through the TIMER database. The results showed that the expression of ZNF668 in RCC was higher than that in normal tissues (P < 0.001). The high expression of ZNF668 is clinically relevant, such as tumor stage (P = 0.001) and TNM classification (T: P = 7.37 e-04; N: P = 0.008; M: P < 0.001). Survival analysis showed that patients with high ZNF668 expression had a significantly poor prognosis (P = 0.023). Univariate analysis showed a significant decrease in overall survival in RCC patients with high ZNF668 expression (P = 0.023). Immuno-cell infiltration showed a significant decrease in CD4+ T cell and dendritic cell infiltration in RCC patients with high expression of ZNF668. GO/KEGG analysis showed that multiple pathways were differentially enriched in the high expression pathway of ZNF668, such as complement activation, and estrogen signaling pathway. In conclusion, high ZNF668 expression is a predictor in RCC.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Proteínas Supressoras de Tumor/genética , Idoso , Biomarcadores Tumorais , Linfócitos T CD4-Positivos/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Proteínas do Sistema Complemento/agonistas , Células Dendríticas/metabolismo , Estrogênios/metabolismo , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Transdução de Sinais/fisiologia , Análise de Sobrevida
4.
J Oral Pathol Med ; 51(5): 474-482, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35377493

RESUMO

BACKGROUND: Oral submucosal fibrosis (OSF) is a precancerous condition that closely related to the habit of chewing betel nut. The OSF patients of 3%-19% may develop cancer, and this probability is increasing year by year. Epigenetics modifications have been reported as part of the pathogenesis of OSF. However, in OSF field, the role and mechanism of arecoline-induced activation of transforming growth factor ß (TGF-ß) signaling on N6-methyladenosine (m6A) modification remain unclear. In this study, we investigated the effect and mechanism of arecoline on m6A modification. METHODS: MeRIP-Seq and RNA-seq were performed in arecoline-stimulated cells. Quantitative polymerase chain reaction and western blot were performed to detect the expression of m6A writers and erasers. CCK-8 and flow cytometry analyses were performed to measure the cell viability and apoptosis. RESULTS: m6A level was increased in OSF tissues compared to normal tissues; arecoline promoted the m6A methyltransferase Mettl3 and Mettl14 through TGF-ß. MeRIP-seq and RNA-seq analyses found that MYC was the target gene of Mettl14. In addition, Mettl14 silence reversed the effects of arecoline on cell proliferation and apoptosis in Hacat cells. CONCLUSION: TGF-ß-METTL14-m6A-MYC axis was crucially implicated in arecoline-mediated OSF and may be an effective therapeutic strategy for OSF treatment.


Assuntos
Arecolina , Fibrose Oral Submucosa , Adenosina/análogos & derivados , Adenosina/metabolismo , Arecolina/farmacologia , Humanos , Metiltransferases/genética , Fibrose Oral Submucosa/induzido quimicamente , Fibrose Oral Submucosa/genética , Fator de Crescimento Transformador beta
5.
Med J Aust ; 216(2): 96-102, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35034365

RESUMO

•Of the women who gave birth in Australia in 2018, 47% had overweight or obesity, with obesity being associated with both maternal and fetal complications. •Bariatric surgery improves fertility and some pregnancy-related outcomes. •Following bariatric surgery, pregnancy should be delayed by at least 12-18 months due to adverse pregnancy outcomes associated with rapid weight loss. •Contraception should be prescribed after bariatric surgery, although the effectiveness of the oral contraceptive pill may be reduced due to malabsorption and contraceptive devices such as intrauterine devices should be considered as first line therapy. •After bariatric surgery, women should undergo close monitoring for nutritional insufficiencies before, during and after pregnancy. Expert opinion recommends these women undergo dietary assessment and supplementation to prevent micronutrient deficiencies. •Bariatric surgeons, bariatric medical practitioners, bariatric dieticians, the patient's usual general practitioner, obstetricians, and maternity specialists should be involved to assist in the multidisciplinary management of these complex patients.


Assuntos
Cirurgia Bariátrica , Obesidade/cirurgia , Complicações na Gravidez/prevenção & controle , Austrália , Anticoncepção , Feminino , Fertilidade , Humanos , Obesidade/complicações , Período Pós-Operatório , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez
6.
Int Orthop ; 46(5): 1145-1154, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35124710

RESUMO

BACKGROUND: Over the last 20 years, suprapatellar (SP) intramedullary nailing has gained considerable attention for treating tibia fractures and is believed to improve fracture alignments, decrease anterior knee pain, and facilitate intraoperative fluoroscopy. However, it is associated with various concerns, including the need to make another infrapatellar (IP) incision to remove the nail. AIMS: This study was aimed at developing a new technique for the removal of SP tibial nails through an SP approach using a cannulated extraction system. The efficiency of the novel SP approach was compared to that of the traditional IP approach for the removal of SP tibial nails. PATIENTS AND METHODS: This was a retrospective cohort study from a prospectively collected clinical registry. The data for 69 consecutive patients who received surgery to remove a previous SP intramedullary nail using an SP approach (n = 30, SP cohort) or an IP approach (n = 39, IP cohort) were analyzed. Intra-operative evaluations included intraoperative blood loss, operation time, and changes in the surgical procedures. At six months follow-up, post-operative Lysholm knee score, visual analog scale (VAS) score, and the active range of motion (ROM) of the affected knee and complications were assessed. RESULTS: Patients in the SP cohort exhibited an increased post-operative Lysholm knee score (ß, 2.6; 95% confidence interval [CI], 0.6 to 4.6; P = 0.012), decreased post-operative VAS score (ß, - 0.7; 95% CI, - 1.1 to - 0.2; P = 0.004), and increased operation time (ß, 9.8 minutes; 95% CI, 5.7 to 14.0 minutes; P < 0.001) compared with those treated with the IP approach after adjustment for baseline characteristics. There were no statistically significant differences in blood loss, post-operative ROM, or complications between the two cohorts. CONCLUSIONS: Compared with the IP technique, the SP approach for the removal of an SP tibial nail was independently associated with an increased post-operative Lysholm knee score and decreased VAS score, although the surgery was longer in duration. The novel technique offers a reliable and minimally invasive option for the removal of an SP tibial nail.


Assuntos
Fixação Intramedular de Fraturas , Fraturas da Tíbia , Pinos Ortopédicos , Estudos de Coortes , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/métodos , Humanos , Estudos Retrospectivos , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
7.
J Orthop Traumatol ; 23(1): 53, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443615

RESUMO

BACKGROUND: Malalignment is a common event during the intramedullary nailing (IMN) of distal tibia fractures (DTFs). Although it is reported that the semi-extended IMN techniques such as suprapatellar (SP) and parapatellar (PP) approaches may be superior in preventing malalignment, the application of these techniques is concerning owing to the intra-articular involvement. We thus developed an extra-articular semi-extended infrapatellar (SEIP) approach which utilizes the infrapatellar (IP) space while maintaining the knee in a semi-extended position. However, there are no studies on the safety and efficacy of SEIP in treating DTFs. Therefore, in this study, the SEIP technique was examined, particularly in terms of the potential alignment improvement of DTFs, and this technique was compared with the traditional hyperflexed infrapatellar (HFIP) procedure. MATERIALS AND METHODS: This randomized clinical trial (RCT) compared IMN malalignment while correcting extraarticular and nondisplaced intra-articular DTFs between April 2018 and June 2021 using the HFIP and SEIP techniques at a level I trauma center in China. The study participants were clinically and radiographically examined for at least 12 months of follow-ups. Intraoperative fluoroscopy time, operation time, blood loss, hospitalization duration, functional ankle score, and complications were assessed as well. RESULTS: Among the 88 recruited participants, 45 (51%) underwent traditional HFIP IMN and 43 (49%) underwent SEIP IMN. Malalignment occurred in 9 patients (20.0%) from the HFIP cohort and in 2 patients (4.7%) from the SEIP cohort (P value = 0.030). In addition, the SEIP IMN technique significantly reduced the intraoperative fluoroscopy time, operation time, and improved the postoperative ankle function compared to the HFIP IMN technique. However, the intraoperative blood loss, hospitalization duration, infection, delay union, and nonunion remained the same between the two cohorts. CONCLUSIONS: In summary, we demonstrated that the SEIP IMN provides markedly enhanced alignment of extraarticular and nondisplaced intra-articular DTFs compared to the traditional HFIP IMN procedure. The described technique represents an effective option for IMN of DTFs. LEVEL OF EVIDENCE: Level 2. Trial registration The Chinese Clinical Trial Registry, ChiCTR2100043673. Registered 26 February 2021, retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=122263.


Assuntos
Fraturas do Tornozelo , Fixação Intramedular de Fraturas , Fraturas da Tíbia , Humanos , Tíbia , Fraturas da Tíbia/cirurgia , Articulação do Tornozelo
8.
Int Orthop ; 45(10): 2719-2726, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33559052

RESUMO

PURPOSE: The semi-extended tibial intramedullary nailing method would enable easier and improved reductions for tibial fractures as well as facilitate fluoroscopic imaging; however, its in-articular nature remains controversial. The aim of this study was to compare the clinical and functional outcomes of the semi-extended infrapatellar (SEIP) approach and hyper-flexed infrapatellar (HFIP) approach for intramedullary nailing to treat tibial shaft fractures. METHODS: This study involved the retrospective analysis of the medical records of patients with tibial shaft fractures that were fixed through either the SEIP approach or the HFIP approach of intramedullary nailing and who were admitted to a level 1 trauma centre. The minimum patient follow-up period was 12 months and the clinical and functional outcomes were estimated at the 12-month visit. RESULTS: Of the 80 patients whose medical records were analyzed, 40 (50%) underwent SEIP nailing and the remaining 40 (50%) underwent the traditional HFIP nailing. Compared with the HFIP group, patients in the SEIP group had a higher Lysholm knee score (median, 92 [interquartile range, 88-95] vs median, 88 [interquartile range, 81-92]; p = .01), a shorter intra-operative fluoroscopy time (median, 93 [interquartile range, 78-105] s, vs median, 136 [interquartile range, 110-157] s; p < .001), and operation time (mean, 88.1 [SD, 17.8] min vs mean, 98.7 [SD, 19.3] min; p = .01). The VAS score was significantly lower in the SEIP group (median, 0; interquartile range, 0-0) than in the HFIP group (median, 0; interquartile range, 0-2) (p = .03). There were two cases (5%) in the SEIP group and 10 cases (25%) in the HFIP group of moderate AKP (p = .03). Meanwhile, there was no significant difference in malalignment, nonunion, delayed union, infection, and other complications, as well as SF-36 physical and mental scores. CONCLUSION: We found that the SEIP approach to tibia intramedullary nailing was superior to the HFIP approach based on the intra-operative and post-operative outcomes. Thus, this novel technique provides an infrapatellar option for semi-extended tibial nailing.


Assuntos
Fixação Intramedular de Fraturas , Fraturas da Tíbia , Pinos Ortopédicos , Humanos , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
9.
Nanotechnology ; 30(8): 085403, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30248023

RESUMO

The unique tunable bandgaps and straightforward synthesis of colloidal quantum dots make them promising low-cost materials for photovoltaics. High-performance colloidal quantum dot solar cells rely on good-quality electron transporting layers (ETLs) to make carrier selective contacts. Despite extensive use of n-type oxides as ETLs, a detailed understanding of their surface and interface states as well as mechanisms to improve their optical properties are still under development. Here, we report a simple procedure to produce MgCl2 passivated ZnO nanoparticles ETLs that show improved device performance. The MgCl2 treated ZnO electron transporting layers boost the PbS colloidal quantum dot cell efficiency from 6.3% to 8.2%. The cell exhibits reduced defects leading to significant improvements of both FF and J sc. This low-temperature MgCl2 treated ZnO electron transporting layer may be applied in solution processed tandem cells as a promising strategy to further increase cell efficiencies.

10.
Proc Natl Acad Sci U S A ; 113(37): E5454-63, 2016 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-27573839

RESUMO

Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCR-CD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCR-CD3 complexes. We found that only TCR-CD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCR-pMHC affinity determined the density of TCR-CD3 clusters, which scaled with overall phosphorylation levels. Thus, TCR-CD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination.


Assuntos
Antígenos/imunologia , Complexo CD3/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Imunidade Adaptativa/genética , Animais , Antígenos/genética , Humanos , Camundongos , Peptídeos/imunologia , Fosforilação/imunologia , Transdução de Sinais , Imagem Individual de Molécula
12.
Clin Sci (Lond) ; 130(5): 349-63, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26574480

RESUMO

Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.


Assuntos
Injúria Renal Aguda/fisiopatologia , Proteínas Reguladoras de Apoptose/fisiologia , Rim/irrigação sanguínea , Traumatismo por Reperfusão/fisiopatologia , Injúria Renal Aguda/etiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Idoso , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Digitoxina/farmacologia , Feminino , Fibrose , Técnicas de Silenciamento de Genes/métodos , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Rim/metabolismo , Rim/patologia , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ratos Sprague-Dawley , Regeneração/fisiologia , Traumatismo por Reperfusão/complicações , Transdução de Sinais/fisiologia , Fatores de Transcrição , Regulação para Cima/efeitos dos fármacos , Proteínas de Sinalização YAP , Adulto Jovem
13.
Medicine (Baltimore) ; 103(19): e37999, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728502

RESUMO

Glioma is a typical malignant tumor of the nervous system. It is of great significance to identify new biomarkers for accurate diagnosis of glioma. In this context, THOC6 has been studied as a highly diagnostic prognostic biomarker, which contributes to improve the dilemma in diagnosing gliomas. We used online databases and a variety of statistical methods, such as Wilcoxon rank sum test, Dunn test and t test. We analyzed the mutation, location and expression profile of THOC6, revealing the network of THOC6 interaction with disease. Wilcoxon rank sum test showed that THOC6 is highly expressed in gliomas (P < 0.001). Dunn test, Wilcoxon rank sum test and t test showed that THOC6 expression was correlated with multiple clinical features. Logistic regression analysis further confirmed that THOC6 gene expression was a categorical dependent variable related to clinical features of poor prognosis. Kaplan-Meier survival analysis showed that the overall survival (OS) of glioma patients with high expression of THOC6 was poor (P < 0.001). Both univariate (P < 0.001) and multivariate (P = 0.04) Cox analysis confirmed that THOC6 gene expression was an independent risk factor for OS in patients with glioma. ROC curve analysis showed that THOC6 had a high diagnostic value in glioma (AUC = 0.915). Based on this, we constructed a nomogram to predict patient survival. Enrichment analysis showed that THOC6 expression was associated with multiple signal pathways. Immuno-infiltration analysis showed that the expression of THOC6 in glioma was closely related to the infiltration level of multiple immune cells. Molecular docking results showed that THOC6 might be the target of anti-glioma drugs. THOC6 is a novel diagnostic factor and prognostic biomarker of glioma.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Biologia Computacional , Glioma , Simulação de Acoplamento Molecular , Proteínas de Ligação a RNA , Feminino , Humanos , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Biologia Computacional/métodos , Glioma/genética , Glioma/patologia , Estimativa de Kaplan-Meier , Prognóstico , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
14.
PLoS One ; 19(5): e0301358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771804

RESUMO

Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 µg/mL and 16 µg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.


Assuntos
Antibacterianos , Escherichia coli , Nanopartículas Metálicas , Platina , Rutênio , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Platina/química , Platina/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Rutênio/química , Rutênio/farmacologia , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Peroxidase/metabolismo , Peróxido de Hidrogênio/química , Catálise , Humanos
15.
Int J Surg Case Rep ; 115: 109291, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38280343

RESUMO

INTRODUCTION AND IMPORTANCE: We present the case of a 17 years old girl with per rectal haemorrhage secondary to pelvic arteriovenous malformations (AVM) and potentially haemorrhoids. Pelvic AVMs are rare and extremely variable in their clinical presentation, size and location and pose a therapeutic challenge. Focus has turned towards interventional radiological procedures with angioembolisation as the main treatment form for pelvic AVMs. CASE PRESENTATION: A 17 years old girl presented to a rural hospital with significant per rectal bleeding requiring transfer to a tertiary centre with interventional radiology capabilities. Diagnostic imaging determined the presence of a pelvic AVM as well as haemorrhoid. She had no prior history of haemorrhoids, per rectal bleeding or per vaginal bleeding. Further diagnostic imaging including a digital subtraction angiography and MRI pelvis was performed and her case was discussed at a multidisciplinary meeting where the decision was made for angioembolisation of a large right rectal AVM as well as precautionary banding of haemorrhoids that had developed secondary to outflow obstruction. A repeat CT mesenteric angiogram a month later demonstrated diminished appearances of the rectal AVM. CLINICAL DISCUSSION: Pelvic AVMs are a rare entity and are not a common cause for per rectal bleeding. There is currently no direct consensus on the optimum management of complex pelvic AVMs particularly those that present with a second pathology such as haemorrhoids. Surgical management often results in recurrence or rapid progression of the AVM lesion and recruitment of new blood supply further complicates the problem. Selective embolisation allows for control of haemorrhage and utilises chemical agents as well as detachable coils and balloons. However, postoperative pain and swelling can still be expected and multiple transcatheter embolisations may be required. CONCLUSION: The treatment of symptomatic pelvic AVMs is complex and requires a multidisciplinary approach with careful radiological planning prior to embolisation. Angioembolisation is becoming increasingly prevalent and multiple embolisation procedures may be required to reach the desired therapeutic effect.

16.
ACS Appl Mater Interfaces ; 16(29): 37486-37496, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38989830

RESUMO

Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn2+, which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.


Assuntos
Exossomos , Fibroínas , Lipopolissacarídeos , Células-Tronco Mesenquimais , Agulhas , Úlceras Orais , Fibroínas/química , Fibroínas/farmacologia , Animais , Lipopolissacarídeos/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Exossomos/metabolismo , Exossomos/química , Camundongos , Úlceras Orais/patologia , Úlceras Orais/tratamento farmacológico , Úlceras Orais/terapia , Úlceras Orais/metabolismo , Células RAW 264.7 , Masculino , Antibacterianos/química , Antibacterianos/farmacologia , Zeolitas/química , Zeolitas/farmacologia
17.
J Surg Case Rep ; 2024(4): rjae195, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572291

RESUMO

Actinomycosis remains a rare and often underdiagnosed cause of appendicitis with only 10% of cases diagnosed prior to surgery. It is an important cause to consider particularly in the setting of an indolent infection with nonspecific symptoms. We present a 22 years old male who presented with 3 weeks history of lower abdominal pain who underwent laboratory investigations and imaging studies suggestive of acute appendicitis. He underwent an emergency laparoscopic caecectomy with histopathology of the specimen suggestive of actinomycosis. He recovered well postoperatively and was discharged home with a prolonged course of oral penicillins. Preoperative diagnosis of actinomycosis is uncommon and accounts for ~10% of cases. Definitive diagnosis is usually through histopathology or tissue/fluid culture. Treatment usually involves a combination of surgical resection and antibiotic therapy with a success rate of >90%.

18.
J Cancer ; 15(5): 1182-1190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356714

RESUMO

Background: Oral Submucosal Fibrosis (OSF) and Oral Leukoplakia (OLK) are well-known oral potentially malignant disorders, and cases of Oral Submucosal Fibrosis concomitant Oral Leukoplakia (OSF+OLK) are now being reported clinically. DNA image cytometry is an objective and non-invasive method for monitoring the risk of precancerous lesions in the oral cavity. Methods: A total of 111 patients with clinically characterized oral mucosal lesions underwent simultaneous and independent histopathological and DNA imaging cytometry assessments. Clinical data were also collected for each patient. Results: The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.003) for OLK. The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.035) for OSF+OLK. The differences of DNA content abnormality in age, sex, dietary habit, smoking, and alcohol intake were not observed in OLK and OSF+OLK. The study indicates an association between DNA content abnormality and pathological examination in OSF+OLK ( χ2 test, P = 0.007). OLK showed higher sensitivity and specificity than OSF, while the sensitivity and specificity of OSF+OLK are higher than OLK only and OSF only. Conclusion: DNA image cytometry can be utilized as an adjunctive device for the initial detection of oral potentially malignant disorders that require further clinical management.

19.
Heliyon ; 10(6): e27451, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496844

RESUMO

The role of traditional Chinese medicine (TCM) in treating diseases is receiving increasing attention. Chinese herbal medicine is an important part of TCM with various applications and the active ingredients extracted from Chinese herbal medicines have physiological and pathological effects. Tissue engineering combines cell biology and materials science to construct tissues or organs in vitro or in vivo. TCM has been proposed by the World Health Organization as an effective treatment modality. In recent years, the potential use of TCM in tissue engineering has been demonstrated. In this review, the classification and efficacy of TCM active ingredients and delivery systems are discussed based on the TCM theory. We also summarized the current application status and broad prospects of Chinese herbal active ingredients in different specialized biomaterials in the field of tissue engineering. This review provides novel insights into the integration of TCM and modern Western medicine through the application of Chinese medicine in tissue engineering and regenerative medicine.

20.
Int J Biol Macromol ; 266(Pt 1): 131221, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554926

RESUMO

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.


Assuntos
Gelatina , Ácido Hialurônico , Metacrilatos , Mucosa Bucal , Agulhas , Úlceras Orais , Cicatrização , Ácido Hialurônico/química , Gelatina/química , Animais , Úlceras Orais/tratamento farmacológico , Úlceras Orais/patologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Metacrilatos/química , Cicatrização/efeitos dos fármacos , Ratos , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Masculino , Camundongos , Humanos
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