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1.
Mater Today Bio ; 26: 101035, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38586871

RESUMO

Liposomes have been widely studied as drug carriers for clinical application, and the key issue is how to achieve effective delivery through targeting strategies. Even though certain cell-level targeting or EPR effect designs have been developed, reaching sufficient drug concentration in intracellular regions remains a challenge due to the singularity of functionality. Herein, benefiting from the unique features of tumor from tissue to cell, a dual-thermosensitive and dual-targeting liposome (DTSL) was creatively fabricated through fine microstructure tailoring, which holds intelligent both tissue-regulated active-to-passive binding and membrane-derived homologous-fusion (HF) properties. At the micro level, DTSL can actively capture tumor cells and accompany the enhanced HF effect stimulated by self-constriction, which achieves a synergistic promotion effect targeting tissues to cells. As a result, this first active-then passive targeting process makes drug delivery more accurate and effective, and after dynamic targeting into cells, the nucleus of DTSL undergoes further thermally responsive contraction, fully releasing internal drugs. In vivo experiments showed that liposomes with dual targeting and dual thermosensitive features almost completely inhibited tumor growth. Summarized, these results provide a reference for a rational design and microstructural tailoring of the liposomal co-delivery system of drugs, suggesting that active-to-passive dual-targeting DTSL can function as a new strategy for cancer treatment.

2.
EClinicalMedicine ; 71: 102579, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38618203

RESUMO

Background: In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. Methods: This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18-75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2-3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4-6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. Findings: 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6-100%), and the objective response rate was 83.3% (95% CI, 68.6-93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5-60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. Interpretation: The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. Funding: The China Anti-Cancer Association and the "Leading Goose" Research and Development Project of Zhejiang Province.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 282-288, 2024 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-38557381

RESUMO

OBJECTIVES: To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing cell differentiation and apoptosis. METHODS: SH-SY5Y cells were divided into control group, low concentration (0.1 µM and 1 µM) adapalene groups, and high concentration (10 µM) adapalene group. Time-lapse microscopy was used to observe the morphological changes of SH-SY5Y cells. Immunofluorescence staining was performed to detect the expression of neuronal specific marker ßIII-tubulin and mature neuronal marker neurofilament heavy polypeptide (NFH). Multi-electrode array was used to record the electrophysiological features of SH-SY5Y cells. Cell apoptosis was evaluated using a cell apoptosis detection kit. RESULTS: Low concentrations of adapalene promoted the formation of neurite outgrowth in SH-SY5Y cells, with the neurites interconnected to form a network. Spontaneous discharge activity was observed in SH-SY5Y cells treated with low concentrations of adapalene. Compared to the control group, the expression of ßIII-tubulin and NFH increased in the 1 µM adapalene group, while the level of cell apoptosis increased in the high concentration adapalene group (P<0.05). CONCLUSIONS: Low concentrations of adapalene can induce differentiation of SH-SY5Y cells into mature functional neurons, while high concentrations of adapalene can induce apoptosis in SH-SY5Y cells.


Assuntos
Neuroblastoma , Tubulina (Proteína) , Humanos , Neurônios , Diferenciação Celular , Apoptose , Linhagem Celular Tumoral
4.
Front Oncol ; 14: 1346290, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357198

RESUMO

Background: Gallbladder neuroendocrine carcinoma (GB-NEC) is an extremely rare cancer with a poor prognosis in the clinic. Although surgical resection remains the primary and preferred therapeutics, many patients are in a late stage and lose the opportunity for surgery. However, due to the extremely low morbidity, the specific treatment guidelines for GB-NEC have not been established. Case presentation: A 52-year-old woman was admitted to our hospital with the chief complaint of "almost 1 month after palliative surgery for metastatic gallbladder carcinoma." According to the results of pathological findings and imaging manifestations, the patient was diagnosed with GB-NEC with a clinical stage of pT3N1M1 (IVB). The patient then received tislelizumab plus EP chemotherapy (etoposide 100 mg + cisplatin 30 mg, d1-3) every 3 weeks for 8 cycles from 12 November, 2021, followed by maintenance therapy (tislelizumab alone) every 3 weeks until now. The tumor response was evaluated as complete remission since 13 February, 2023. As of the last follow-up, the patient remains alive, with no complaints of discomfort. Conclusions: Gallbladder NEC has no specific symptoms, and the diagnosis is based on pathological and immunohistochemical results. The therapeutic course and efficacy of the case in this study indicates that the application of PD-1 inhibitor might be a feasible therapeutic option for GB-NEC. However, this potential strategy needs validation by further clinical studies in the future.

5.
Molecules ; 29(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38257322

RESUMO

Five artemisinin bivalent ligands molecules 4a-4e were designed, synthesized, and confirmed by 1H NMR, 13C NMR, and low-resolution mass spectrometry, and the bioactivities of the target compounds were investigated against four human tumor cell lines in vitro, including BGC-823, HepG-2, MCF-7, and HCT-116. The results showed 4a, 4d, and 4e exhibited significantly tumor cell inhibitory activity compared with the artemisinin and dihydroartemisinin; compound 4e has good biological activity inhibiting BGC-823 with an IC50 value of 8.30 µmol/L. Then, the good correlations with biological results were validated by molecular docking through the established bivalent ligands multi-target model, which showed that 4e could bind well with the antitumor protein MMP-9.


Assuntos
Artemisininas , Humanos , Simulação de Acoplamento Molecular , Artemisininas/farmacologia , Linhagem Celular Tumoral , Ligantes
6.
Artigo em Inglês | MEDLINE | ID: mdl-38216548

RESUMO

OBJECTIVES: Our purpose is to evaluate the patterns of organ metastasis and the prognosis in lung adenosquamous carcinoma patients with organ metastasis. METHODS: We collected the data from the surveillance epidemiology and end results database, covering the period of 2000-2018. Cox regression, Kaplan-Meier and log-rank analyses were performed. RESULTS: Totally, 2698 patients were enrolled, comprising 851 (31.54%) patients diagnosed with organ metastasis and 2017 (68.46%) patients without organ metastasis. Patients with distant organ metastasis show a significant decrease in median overall survival. In addition to the aforementioned factors, age over 70 years, male, main bronchus, advanced T stage, larger tumour size, absence of primary tumour surgery and lack of radiotherapy have all been identified as prognostic indicators associated with a poorer outcome. In terms of treatment options, patients with organ metastasis can benefit from chemotherapy and primary tumour surgery. Moreover, in patients with organ metastasis, those who received a combination treatment of surgery, chemotherapy and radiotherapy displayed the most favourable prognosis, with a median overall survival of 17 months. CONCLUSIONS: We identified the prognostic indicators for organ metastasis in patients with lung adenosquamous carcinoma. Highly selected patients who undergo a combination treatment of surgery, chemotherapy and radiotherapy may experience the greatest survival benefit.

7.
Int J Nanomedicine ; 18: 7287-7304, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076730

RESUMO

Introduction: Insufficient tumor permeability and inadequate nanoparticle retention continue to be significant limitations in the efficacy of anti-tumor drug therapy. Numerous studies have focused on enhancing tumor perfusion by improvement of tumor-induced endothelial leakage, often known as the enhanced permeability and retention (EPR) effect. However, these approaches have produced suboptimal therapeutic outcomes and have been associated with significant side effects. Therefore, in this study, we prepared tumor cell membrane-coated gold nanorods (GNR@TM) to enhance drug delivery in tumors through homogeneous targeting of tumor cell membranes and in situ real-time photo-controlled therapy. Methods: Here, we fabricated GNR@TM, and characterized it using various techniques including Ultraviolet-Visible (UV-Vis) spectrophotometer, particle size analysis, potential measurement, and transmission electron microscopy (TEM). The cellular uptake and cytotoxicity of GNR@TM were analyzed by flow cytometry, confocal laser scanning microscopy (CLSM), TEM, CCK8 assay and live/dead staining. Tissue drug distribution was determined by inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence staining. Furthermore, to evaluate the therapeutic effect, mice bearing MB49 tumors were intravenously administered with GNR@TM. Subsequently, near-infrared (NIR) laser therapy was performed, and the mice's tumor growth and body weight were monitored. Results: The tumor cell membrane coating endowed GNR@TM with extended circulation time in vivo and homotypic targeting to tumor, thereby enhancing the accumulation of GNR@TM within tumors. Upon 780 nm laser, GNR@TM exhibited excellent photothermal conversion capability, leading to increased tumor vascular leakage. This magnification of the EPR effect induced by NIR laser further increased the accumulation of GNR@TM at the tumor site, demonstrating strong antitumor effects in vivo. Conclusion: In this study, we successfully developed a NIR-triggered nanomedicine that increased drug accumulation in tumor through photo-controlled therapy and homotypic targeting of the tumor cell membrane. GNR@TM has been demonstrated effective suppression of tumor growth, excellent biocompatibility, and significant potential for clinical applications.


Assuntos
Antineoplásicos , Hipertermia Induzida , Nanotubos , Neoplasias , Camundongos , Animais , Terapia Fototérmica , Antineoplásicos/farmacologia , Neoplasias/terapia , Sistemas de Liberação de Medicamentos/métodos , Ouro/química , Nanotubos/química , Linhagem Celular Tumoral
8.
Trials ; 24(1): 789, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053197

RESUMO

BACKGROUND: Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial. METHODS: One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire. DISCUSSION: This study improves cancer patients' quality of life and provides clinical evidence. TRIAL REGISTRATION: Registered at ClinicalTrials.gov- NCT05397457 on 1 June 2022.


Assuntos
Neoplasias da Mama , Terapia com Luz de Baixa Intensidade , Humanos , Feminino , Qualidade de Vida , Dispositivos de Proteção da Cabeça , Alopecia/induzido quimicamente , Alopecia/prevenção & controle , Alopecia/tratamento farmacológico , Couro Cabeludo , Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
BMC Musculoskelet Disord ; 24(1): 884, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37957622

RESUMO

PURPOSE: The position of the acetabular and femoral components is critical for stability and wear resistance. The aim of this study is to investigate whether the fluoroscopy-guided direct anterior approach in the supine position (S-DAA) is more helpful in improving the position of acetabular and femoral components than the fluoroscopy-guided direct anterior approach in the lateral decubitus position (L-DAA). METHODS: A retrospective analysis of 76 cases of fluoroscopy-guided direct anterior approach total hip arthroplasty (38 cases in the S-DAA and 38 cases in the L-DAA group) was performed in one hospital from 2019 to 2021. The differences in inclination, anteversion, femoral offset (FO), global offset (GO), and leg length discrepancy (LLD) measurements during and after surgery were analyzed. The postoperative femoral offset (FO), global offset (GO), leg length discrepancy (LLD), and preoperative and postoperative Harris hip score were compared between the two groups. RESULTS: In the S-DAA group, there were no significant differences in the mean intraoperative inclination angle anteversion angle, FO, GO, and LLD compared to the postoperative values, whereas in the L-DAA group, there were significant differences between the intraoperative and postoperative measurements (P < 0.001, P = 0.009, P<0.001, P<0.001 and P = 0.008, respectively). Additionally, there were significant differences in the accuracy of LLD, FO, and GO between the two groups (P < 0.001). Compared with the L-DAA group, the average differences of inclination, anteversion, LLD, FO, and GO during and after operation in the S-DAA group were smaller, and the consistency was higher. There was a significant difference in Harris hip score between the two groups at 1 week after surgery (P = 0.033). There was no significant difference in Harris hip score between 1 month and 3 months after surgery (P = 0.482 and P = 0.797, respectively). CONCLUSIONS: In the supine group, the direct anterior approach (DAA) provides more accurate positioning of the acetabular and femoral components. However, there was no significant difference in hip joint function and activity between the two groups at follow-up.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Decúbito Dorsal , Acetábulo/cirurgia , Fluoroscopia , Desigualdade de Membros Inferiores/diagnóstico por imagem , Desigualdade de Membros Inferiores/etiologia , Desigualdade de Membros Inferiores/cirurgia
10.
Ear Nose Throat J ; : 1455613231205442, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902176

RESUMO

Objective: To explore the clinical features, diagnosis, and treatment strategies for otogenic brain abscesses (OBA). Methods: Clinical data from 10 patients with OBA were analyzed retrospectively. Clinical characteristics, diagnosis, and treatment experiences were summarized. Results: Two were first diagnosed in the Department of Otorhinolaryngology, 5 in Neurosurgery, and 3 in other departments. There were 6 cases of temporal lobe abscess and 4 cases of cerebellar abscesses. Five cases were accompanied by 1 or more intracranial complications. Headache is a common presentation in all cases. The main pathogenic bacteria were anaerobic bacteria. All patients had no previous ear or brain surgery history, and no history of traumatic brain injury, 7 received surgical treatment in the neurosurgery and/or otolaryngology department. Two patients died, the other 8 fully recovered and so were discharged. Conclusions: Diagnosis and treatment of OBA must involve multiple departments. Multidisciplinary consultation (MDT) is crucial to the success of the first OBA diagnosis. The diagnosis and treatment team develops personalized treatment plans by integrating MDT treatment opinions and combining the actual condition of patients, thereby making the diagnosis and treatment of OBA accurate and timely.

11.
Medicine (Baltimore) ; 102(40): e35104, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800780

RESUMO

Cardiovascular mortality (CVM) is a growing concern for cancer survivors. This study aimed to investigate the mortality patterns of individuals with typical carcinoid (TC) tumors, identify independent predictors of CVM, and compare these risk variables with those associated with TC deaths. The Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019 was utilized for obtaining data on patients with TC. Standardized mortality rates were employed to evaluate the risk of CVM while multivariate competing risk models were used to determine the association between patient characteristics and the probability of CVM or TC-related deaths. Our findings show that TC patients had an increased risk of CVM, with an standardized mortality rates of 1.12 (95% CI:1.01-1.25). Furthermore, we discovered that age at diagnosis, marital status, year of diagnosis, SEER stage, site, year of diagnosis, surgery, radiotherapy, and chemotherapy all contributed independently to the risk of CVM in patients with TC, whereas age at diagnosis, sex, race, SEER stage, site, year of diagnosis, surgery, radiotherapy, and chemotherapy all contributed significantly to TC mortality. Compared to the general population in the United States, patients with TC are significantly more likely to acquire CVM. Timely introduction of cardioprotective treatments is critical for preventing CVM in patients with TC.


Assuntos
Sobreviventes de Câncer , Tumor Carcinoide , Neoplasias Pulmonares , Humanos , Estados Unidos/epidemiologia , Programa de SEER , Medição de Risco , Pulmão
12.
Heliyon ; 9(10): e20337, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37767466

RESUMO

Background: Deep learning methods are increasingly applied in the medical field; however, their lack of interpretability remains a challenge. Captum is a tool that can be used to interpret neural network models by computing feature importance weights. Although Captum is an interpretable model, it is rarely used to study medical problems, and there is a scarcity of data regarding MRI anatomical measurements for patients with prostate cancer after undergoing Robotic-Assisted Radical Prostatectomy (RARP). Consequently, predictive models for continence that use multiple types of anatomical MRI measurements are limited. Methods: We explored the energy efficiency of deep learning models for predicting continence by analyzing MRI measurements. We analyzed and compared various statistical models and provided reference examples for the clinical application of interpretable deep-learning models. Patients who underwent RARP at our institution between July 2019 and December 2020 were included in this study. A series of clinical MRI anatomical measurements from these patients was used to discover continence features, and their impact on continence was primarily evaluated using a series of statistical methods and computational models. Results: Age and six other anatomical measurements were identified as the top seven features of continence by the proposed model UINet7 with an accuracy of 0.97, and the first four of these features were also found by primary statistical analysis. Conclusions: This study fills the gaps in the in-depth investigation of continence features after RARP due to the limitations of clinical data and applicable models. We provide a pioneering example of the application of deep-learning models to clinical problems. The interpretability analysis of deep learning models has the potential for clinical applications.

13.
Zool Res ; 44(5): 894-904, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37551137

RESUMO

Conjugative transfer of antibiotic resistance genes (ARGs) by plasmids is an important route for ARG dissemination. An increasing number of antibiotic and nonantibiotic compounds have been reported to aid the spread of ARGs, highlighting potential challenges for controlling this type of horizontal transfer. Development of conjugation inhibitors that block or delay the transfer of ARG-bearing plasmids is a promising strategy to control the propagation of antibiotic resistance. Although such inhibitors are rare, they typically exhibit relatively high toxicity and low efficacy in vivo and their mechanisms of action are inadequately understood. Here, we studied the effects of dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, on conjugation. DHA inhibited the conjugation of the IncI2 and IncX4 plasmids carrying the mobile colistin resistance gene ( mcr-1) by more than 160-fold in vitro in Escherichia coli, and more than two-fold (IncI2 plasmid) in vivo in a mouse model. It also suppressed the transfer of the IncX3 plasmid carrying the carbapenem resistance gene bla NDM-5 by more than two-fold in vitro. Detection of intracellular adenosine triphosphate (ATP) and proton motive force (PMF), in combination with transcriptomic and metabolomic analyses, revealed that DHA impaired the function of the electron transport chain (ETC) by inhibiting the tricarboxylic acid (TCA) cycle pathway, thereby disrupting PMF and limiting the availability of intracellular ATP for plasmid conjugative transfer. Furthermore, expression levels of genes related to conjugation and pilus generation were significantly down-regulated during DHA exposure, indicating that the transfer apparatus for conjugation may be inhibited. Our findings provide new insights into the control of antibiotic resistance and the potential use of DHA.


Assuntos
Infecções por Escherichia coli , Camundongos , Animais , Escherichia coli/genética , Infecções por Escherichia coli/veterinária , beta-Lactamases/genética , Antibacterianos/farmacologia , Plasmídeos/genética
14.
Ann Thorac Surg ; 116(5): 1006-1012, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37573993

RESUMO

BACKGROUND: The choice of postoperative pain management for patients who experience moderate to severe acute pain after thoracoscopic surgery is debatable. This study aimed to determine whether paravertebral block (PVB) provides more benefits than thoracic epidural analgesia (TEA) for thoracoscopic surgery. METHODS: From February 2020 to April 2022, patients without chronic pain who were scheduled to undergo thoracoscopic surgery were randomly assigned to the PVB group or the TEA group. The visual analogue scale score was used to measure the degree of pain when the patients were at rest or coughing. RESULTS: In total, 176 eligible patients were enrolled in this study. No significant difference in the visual analogue scale score was found between the 2 groups at rest (P = .395) or with coughing (P = .157). Additionally, there was no significant difference in the average pain score between these 2 states (P = .221). The median time for catheter placement in the PVB group was 5 minutes, which was shorter than that (14 minutes) in the TEA group (P < .001). Moreover, the catheter placement failure rate in the PVB group was lower than that in the TEA group (P = .038). The incidence of hypotension (P = .016) and urinary retention (P = .006) in the PVB group was lower than that in the TEA group. CONCLUSIONS: PVB can provide pain relief that is similar to that of TEA but with no additional puncture pain, a shorter catheter placement time, and fewer side effects in patients undergoing video-assisted thoracoscopic surgery.

15.
Chem Biodivers ; 20(3): e202201090, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36728645

RESUMO

Five new ent-pimarane diterpenes (1-5) and five known analogs (6-10) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC50 values of 16.35±2.59 and 18.86±4.83 µM, respectively.


Assuntos
Abietanos , Diterpenos , Sigesbeckia , Humanos , Abietanos/farmacologia , Abietanos/química , Diterpenos/farmacologia , Diterpenos/química , Estrutura Molecular , Componentes Aéreos da Planta/química , Sigesbeckia/química
18.
Oral Dis ; 29(1): 175-187, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34651389

RESUMO

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. MATERIALS AND METHODS: Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-ß1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. RESULTS: The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-ß1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. CONCLUSIONS: These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-ß1 and oncogenic signaling pathways.


Assuntos
Adenoma Pleomorfo , Carcinoma Adenoide Cístico , Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Humanos , Adenoma Pleomorfo/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Mucoepidermoide/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Neoplasias das Glândulas Salivares/patologia , Proteína do Gene 3 de Ativação de Linfócitos/genética , Receptor A2A de Adenosina/genética
19.
Acta Neurol Belg ; 123(5): 1849-1854, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36103086

RESUMO

OBJECTIVE: Chronic pain is a common symptom experienced by patients after spontaneous epidural hematoma (SSEH), and it seriously affects their quality of life. The outcome and prognosis of chronic pain after SSEH are rarely reported. Thus, we conduct this study to present the outcomes and explore prognostic factors of chronic pain in patients with SSEH. METHODS: We retrospectively reviewed patients diagnosed with SSEH and invited them to complete the American Spinal Injury Association (ASIA) and Neuropathic Pain Symptom Inventory (NPSI) scales. Pearson χ2 and binary logistic regression were used to explore prognostic factors related to chronic pain after SSEH. RESULTS: A total of 55 patients were reviewed; 21 patients (38.2%) were lost to follow-up, 3 patients (5.4%) died, and 31 patients (56.4%) completed the scales, with a mean follow-up time of 20.6 ± 17.3 months. The ASIA and NPSI results showed significant improvement after surgery. Pearson χ2 showed that timely surgery (≤ 12 h) was related to better outcomes (p < 0.05, Fisher test), and binary logistic regression revealed that patients with a preoperative NPSI score of 11-20 were prone to achieving significant pain relief (OR 23.67, 95%CI 1.11-503.48, p = 0.04). CONCLUSION: Chronic pain is a common symptom during follow-up after SSEH, and timely intervention is suggested to obtain satisfactory outcomes. Patients who receive emergent surgery within 12 h or who have a preoperative NPSI score of 11-20 may achieve significant relief of chronic pain.


Assuntos
Dor Crônica , Hematoma Epidural Craniano , Hematoma Epidural Espinal , Neuralgia , Humanos , Hematoma Epidural Espinal/complicações , Hematoma Epidural Espinal/diagnóstico por imagem , Hematoma Epidural Espinal/cirurgia , Resultado do Tratamento , Dor Crônica/etiologia , Estudos Retrospectivos , Qualidade de Vida , Imageamento por Ressonância Magnética , Prognóstico
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