Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
1.
Phytochemistry ; 222: 114096, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641141

RESUMO

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.


Assuntos
Forsythia , Controle de Qualidade , Forsythia/química , Humanos , Frutas/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Animais , Estrutura Molecular
2.
Phytochemistry ; 221: 114064, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508326

RESUMO

Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD50) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application.


Assuntos
Alcaloides , Extratos Vegetais , Animais , Camundongos , Etnofarmacologia , Extratos Vegetais/química , Medicina Tradicional Chinesa , Anti-Inflamatórios , Compostos Fitoquímicos
3.
J Agric Food Chem ; 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37917162

RESUMO

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

4.
Lung Cancer ; 178: 66-74, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36806896

RESUMO

OBJECTIVES: De novo mesenchymal-to-epithelial transition (MET) gene fusions in non-small cell lung cancer (NSCLC) are a promising target for MET tyrosine kinase inhibitors (TKIs). We aimed to examine the response to targeted therapy with MET TKIs and resistance mechanisms in de novo MET fusion-positive NSCLC as these have not been comprehensively explored. MATERIALS AND METHODS: We examined the MET fusions in 4,429 patients with advanced-stage NSCLC using targeted next-generation sequencing and validated the results using RT-PCR. We analyzed cellular models harboring MET fusions and established a patient-derived organoid (PDO) model. RESULTS: We identified 13 (0.29 %, 13/4429) patients with de novo MET fusions and found EPHB4, THAP5, TNPO3, and DST as novel MET fusion partners. The most common concomitant gene with MET fusions was TP53 mutations. Among 12 patients receiving MET TKI treatment, two achieved stable disease, six achieved partial response, and four underwent progressive disease. An in vitro study showed that EPHB4-MET is a functional driver gene. MET inhibitors significantly inhibited the proliferation and phosphorylation of downstream STAT3, AKT, and ERK1/2 in EPHB4-MET overexpressing cells. Acquired MET D1228H/N or D1246N mutations were found in patients harboring MET fusions after acquiring resistance to MET TKIs. Tivantinib showed optimal suppression efficacy in a PDO model with an acquired MET D1228N mutation. CONCLUSION: MET fusions occur in a rare subset of patients with NSCLC and represent a promising therapeutic target. MET secondary mutations D1228H/N or D1246N present the potential resistance mechanisms of MET inhibitors in patients with de novo MET fusions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Mutação , Receptores Proteína Tirosina Quinases/genética , beta Carioferinas/genética
5.
Thorac Cancer ; 14(5): 462-469, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36511202

RESUMO

BACKGROUND: Anatomical variations often pose challenges to pulmonary surgery. Previous studies have mainly described the frequencies of bronchovascular anatomical variations in pulmonary segments, but did not determine the differences between pulmonary segments and the regularity behind these anatomical variations. Here, we attempted to investigate the regularity of bronchovascular anatomical variations in different pulmonary segments. METHODS: Thin-slice enhanced computed tomography data of 800 cases from our center were included in this study. Digitalized three-dimensional virtual lung segmentation was done, the dominant and inferior lung segments of the right upper lobe were defined, and the regularity of anatomical variations was explored. RESULTS: The mean volume ratio of the anterior segment of the right upper lobe (39.6 ± 8.6%) was highest, and that of the posterior segment (28.6 ± 7.9%) was lowest. Therefore, the dominant-type segment (DS + SDS) was dominant in the anterior segment, accounting for 74.6% (597/800), and the inferior-type segment (SIS + IS) was dominant in the posterior segment of the right upper lobe, accounting for 71.5% of cases (573/800). During the transformation of dominant and inferior lung segments, the corresponding regularity of anatomical variations could be displayed. For example, with an increase in the volume of the anterior segment of the right upper lobe, the occurrence rate of the bifurcated type of bronchus (B1 + 2, B3), the "central vein type" and the involvement of the trunk inferior and ascending artery in the blood supply of anterior segment gradually increased. CONCLUSIONS: The existence of dominant segments will increase the diversity of anatomical variations and the complexity of pulmonary segmentectomy.


Assuntos
Procedimentos Cirúrgicos Pulmonares , Veias Pulmonares , Humanos , Pulmão/cirurgia , Artéria Pulmonar , Brônquios/diagnóstico por imagem
6.
Microbiol Res ; 268: 127296, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36580869

RESUMO

The protein lysine acetylation includes acetyl-CoA (AcCoA) or acetyl phosphate (AcP)-mediated nonenzymatic acetylation, and enzymatic acetylation. It is widespread in the proteomes but the acetylation levels of most sites are very low. A thorough understanding of the determinants of low acetylation levels is highly important for elucidating the physiological relevance of lysine acetylation. In this study, we constructed a non-native substrate library containing 24 synthesized polypeptides, and we showed that ATP could inhibit the AcCoA-mediated nonenzymatic acetylation of these polypeptides through LC-MS/MS analysis. The acetyltransferase PatZ could acetylated these non-native substrates, and the PatZ-catalyzed acetylation of the polypeptides was also inhibited by ATP. Furthermore, the Western blot showed that ATP also inhibited the nonenzymatic (AcCoA or AcP-mediated) and enzymatic (PatZ-catalyzed) acetylation of acetyl-CoA synthetase Acs, which is a native substrate for acetylation. ATP can also inhibit the autoacetylation of acetyltransferase PatZ. Besides, both ADP and AMP could enhance the AcP-mediated acetylation of Acs, but ADP slightly inhibited the AcCoA-mediated acetylation of Acs. However, both ADP and AMP had no evident inhibition on the PatZ-catalyzed acetylation of Acs. Based on these results, we proposed that ATP can act as an inhibitor of acetylation, and it may regulate the function of PatZ by inhibiting its autoacetylation and compensate for the function of deacetylase CobB.


Assuntos
Proteínas de Escherichia coli , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Trifosfato de Adenosina/metabolismo , Lisina/metabolismo , Acetilação , Acetilcoenzima A/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Acetiltransferases , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo
7.
J Med Chem ; 65(22): 15028-15047, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36331508

RESUMO

Quinazoline and its derivatives have drawn much attention in the development of potential antitumor agents. Here, we synthesized a series of 1,2,3-triazole derivatives of quinazoline at the C6 position and evaluated for their cytotoxic activity in various human cancer cell lines. We found that compound 5a was the most cytotoxic to HCT-116 cells (IC50, 0.36 µM). Target profiling found that 5a directly binds to both the autophagy-associated protein SQSTM1/P62 and the E3 ligase RNF168, promoting their interaction. Consistently, 5a treatment induces a decrease in RNF168-mediated H2A ubiquitination and compromises homologous recombination-mediated DNA repair, thus increasing the sensitivity of HCT-116 to X-ray radiation. Moreover, 5a suppressed xenografted tumor growth in mice in a dose-dependent manner. Taken together, the 1,2,3-triazole derivative of quinazoline 5a may serve as a novel compound for tumor therapy based on its role in promoting a P62/RNF168 interaction.


Assuntos
Reparo do DNA , Quinazolinas , Triazóis , Animais , Humanos , Camundongos , Células HCT116 , Quinazolinas/farmacologia , Proteína Sequestossoma-1/efeitos dos fármacos , Proteína Sequestossoma-1/metabolismo , Triazóis/farmacologia , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Antineoplásicos/farmacologia
8.
Thorac Cancer ; 13(22): 3174-3182, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36208139

RESUMO

BACKGROUND: Sublobectomy for early-stage non-small cell lung cancer (NSCLC) remains a matter of debate. This study aimed to discuss the feasibility of sublobectomy in patients with pathological-stage IA1-2 confirmed as pathologically invasive but radiologically noninvasive adenocarcinoma. METHODS: From 2011 to 2019, we screened clinical stage IA1-IA2 lung cancer patients who underwent surgery at the Guangdong Provincial People's Hospital (GDPH). Inclusion criteria were maximum tumor diameter of 2.0 cm or less, consolidation tumor ratio (CTR) ≤ 0.25, and pathologically confirmed invasive adenocarcinoma. Sublobectomy (segmentectomy and wedge resection) and lobectomy groups were created, and propensity scores were computed. The primary endpoints were lung cancer-specific overall survival (LCSS) and LCS- relapse-free survival (LCS-RFS) after adjusting propensity scores. RESULTS: A total of 1731 patients were screened, and 100 patients were enrolled. The lobectomy group had 51 patients and the limited resection group had 49. No cases relapsed, and two patients died from nontumor causes. For the entire cohort, the 5-year LCSS and 5-year LCS-RFS were 100% in the lobectomy and limited resection groups. When propensity scores matched, there were no differences in LCSS and LCS-RFS between the two groups (LCSS:100%, LCS-RFS 100% in lobectomy and limited resection, respectively). DISCUSSION: Sublobectomy may be curative for pathologically invasive but radiologically noninvasive adenocarcinoma at pathological stage IA1-2.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Pneumonectomia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia
9.
Thorac Cancer ; 13(15): 2210-2222, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35818719

RESUMO

OBJECTIVE: In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. METHOD: Hospital employees ≥40 years old who underwent low-dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT-imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation-related occupation received monitoring in hospital. RESULT: The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. CONCLUSION: The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Adulto , China/epidemiologia , Detecção Precoce de Câncer/métodos , Feminino , Hospitais , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Fatores de Risco
10.
Transl Lung Cancer Res ; 11(4): 509-522, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35529798

RESUMO

Background: In East Asia, the number of patients with adenocarcinoma, especially those presenting with ground-glass nodules (GGNs), is gradually increasing. Family aggregation of pulmonary GGNs is not uncommon; however, genetic predisposition in these patients remains poorly understood and identification of genes involved in the cause of these early-stage lung cancers might contribute to understanding of the underlying mechanisms and potential prevention strategies. Methods: Fifty patients with early-stage lung adenocarcinoma (LUAD) presenting as GGNs and a first-degree family history of lung cancer (FHLC) from 34 independent families were enrolled into this study. Germline mutations of these patients were analyzed with whole exome sequencing (WES) and compared with age- and sex-matched 39 patients with sporadic lung cancer and 689 local healthy people. We used a stepwise variant filtering strategy, gene-based burden testing, and enrichment analysis to investigate rare but potentially pathogenic heritable mutations. Somatic tumor mutations were analyzed to consolidate germline findings. Results: In total, 1,571 single nucleotide variants (SNVs) and 238 frameshifts with a minor allele frequency (MAF) <0.01, which were rare, recurrent, and potentially damaging candidates, were finally identified through the filtering in the GGN cohort. Pathway analysis showed the extracellular matrix to be the top dysregulated pathway. Gene-based burden testing of these highly disruptive risk-conferring heritable variants showed that MSH5 [odds ratio (OR), 9.28, 95% confidence interval (CI): 2.49-35.87], MMP9 (OR, 8.11, 95% CI: 2.22-28.43), and CYP2D6 (OR, 8.09, 95% CI: 2.68-24.92) were significantly enriched in our cohort (P<0.05). The number of rare damaging germline variants in non-smoking patients was significantly higher than that of smoking-affected patients (Spearman's ρ=-0.39, P=0.02). Conclusions: Heritable, potentially deleterious, and rare candidate variants of MSH5, MMP9 and CYP2D6 were significantly associated with early-stage LUAD presenting with GGNs. Nonsmoking patients likely have a higher genetic predisposition to this type of cancer than smoking-affected patients. These results have extended our understanding of the underlying mechanisms of early-stage LUAD.

11.
J Am Chem Soc ; 144(11): 4776-4782, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35263101

RESUMO

An enantioselective nickel-catalyzed intramolecular reductive cross-coupling of C(sp2) electrophiles and cyano groups is reported. Enantioenriched CN-containing all-carbon quaternary stereocenters are assembled by desymmetrizing cyclization of aryl/alkenyl halide-tethered malononitriles. The use of an organic reductant, (EtO)2MeSiH, is crucial to the enantioselectivity and reactivity. Applications of the method are demonstrated through the synthesis of bioactive molecules and their cyanated analogues and the total synthesis of the natural product diomuscinone. This study exhibits the potential of desymmetrizing reductive coupling strategies to access structurally rigid and synthetically versatile molecules from readily available starting materials.


Assuntos
Carbono , Níquel , Catálise , Ciclização , Estereoisomerismo
12.
Transl Lung Cancer Res ; 10(4): 1711-1719, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012787

RESUMO

BACKGROUND: Some pulmonary nodules are not suitable for computed tomography-guided percutaneous localization. This study aimed to investigate the feasibility and safety of real-time localization for these non-palpable pulmonary nodules using watershed analysis of the target pulmonary artery during thoracoscopic wedge resection. METHODS: Watershed analysis is a novel technique that can be used to create a specific area on the lung surface for nodule localization. This analysis is performed by temporarily blocking the target pulmonary artery and using indocyanine green fluorescence during surgery. In our study, the surgery was simulated and evaluated preoperatively using a high-precision three-dimensional reconstruction model obtained by multidetector spiral computed tomography. The lung was observed using an infrared thoracoscopy system after an intravenous injection of indocyanine green (2.5 mg/mL), and the white-to-blue transitional zone was marked using electrocautery, after which a wedge resection was performed. RESULTS: A total of 25 out of 26 patients underwent successful wedge resection. The mean tumor size and depth based on computed tomography scans were 13.2±6.4 and 12.2±7.8 mm, respectively. The mean operation duration was 142.6±52.8 min. The mean bleeding volume during surgery was 12.9±9.7 mL. The mean drainage tube indwelling time was 35.6±20.0 h, and the median length of postoperative stay was 3 days (range, 2-6 days). CONCLUSIONS: Our experience showed that the watershed analysis of the target pulmonary artery for nodule localization was safe and feasible. It may become an effective and attractive alternative method for localizing non-palpable pulmonary nodules in selected patients undergoing thoracoscopic wedge resection.

13.
Oncol Lett ; 21(5): 390, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33777213

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) is a critical rate-limiting enzyme involved in NAD synthesis that has been shown to contribute to the progression of liver cancer. However, the potential role and mechanism of NAMPT in hepatitis B virus (HBV)-associated liver cancer remain unclear. The present study assessed the expression of NAMPT in HBV-positive and -negative liver cancer cells, and investigated whether HBV-induced NAMPT expression is dependent on HBV X protein (HBx). In addition, the role of NAMPT in HBV replication and transcription, and in HBV-mediated liver cancer cell growth was explored. The effects of NAMPT on the glycolytic pathway were also evaluated. Reverse transcription-quantitative PCR and western blotting results revealed that NAMPT expression levels were significantly higher in HBV-positive liver cancer cells than in HBV-negative liver cancer cells, and this effect was HBx-dependent. Moreover, the activation of NAMPT was demonstrated to be required for HBV replication and transcription. The NAMPT inhibitor FK866 repressed cell survival and promoted cell death in HBV-expressing liver cancer cells, and these effects were attenuated by nicotinamide mononucleotide. Furthermore, the inhibition of NAMPT was associated with decreased glucose uptake, decreased lactate production and decreased ATP levels in HBV-expressing liver cancer cells, indicating that NAMPT may promote the aerobic glycolysis. Collectively, these findings reveal a positive feedback loop in which HBV enhances NAMPT expression and the activation of NAMPT promotes HBV replication and HBV-mediated malignant cell growth in liver cancer. The present study highlights the important role of NAMPT in the regulation of aerobic glycolysis in HBV-mediated liver cancer, and suggests that NAMPT may be a promising treatment target for patients with HBV-associated liver cancer.

14.
Thorac Cancer ; 12(6): 970-973, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33502105

RESUMO

A 48-year-old woman presented to our department and chest computed tomography (CT) revealed five pulmonary nodules, two of which were in the left upper lobe of the lung and three in the superior segment of the left lower lobe., All the lesions were resected for comprehensive histological assessment in order to distinguish synchronous multiple primary lung cancers (SMPLCs) from intrapulmonary metastases. The nodules were all successfully removed by minimally invasive surgery under the guidance of three dimensional (3D) reconstruction, in order to preserve as much lung function for the patient as possible. Postoperative histopathological examination demonstrated the presence of SMPLC. The patient was discharged from hospital on postoperative day 4 without any complications.


Assuntos
Imageamento Tridimensional/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade
15.
Cytotherapy ; 23(1): 57-64, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33218835

RESUMO

BACKGROUND AIMS: Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. METHODS: A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. RESULTS: Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. CONCLUSIONS: The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.


Assuntos
Células-Tronco Mesenquimais , Traumatismos da Medula Espinal/terapia , Cordão Umbilical/citologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Espaço Subaracnóideo/fisiopatologia , Adulto Jovem
16.
World Neurosurg ; 116: e602-e610, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29778600

RESUMO

OBJECTIVE: We sought to evaluate 5-year outcomes between microendoscopy-assisted minimally invasive (MIS) and open transforaminal lumbar interbody fusion (TLIF). METHODS: Sixty single-level MIS and open surgeries were performed (30 patients in either group). Perioperative parameters including operative duration, intraoperative estimated blood loss, fluoroscopy time, postoperative analgesic usage, ambulatory time, and complications were recorded. Visual analog scale (back and leg), Japanese Orthopaedics Association score, and Oswestry Disability Index were obtained. Finally, self-evaluation of surgical outcomes (modified MacNab criteria), interbody fusion rate (Bridwell grade 1), and prevalence of adjacent segment degeneration were assessed. RESULTS: Intraoperative estimated blood loss and postoperative analgesia usage were reduced in the MIS group, and patients undergoing microendoscopy-assisted MIS-TLIF ambulated earlier than those receiving open TLIF postoperatively. Nevertheless, surgical duration and fluoroscopy time were prolonged in the MIS group. Complication incidences were similar in both groups. Visual analog scale (back and leg), Japanese Orthopaedics Association, and Oswestry Disability Index were improved at 1 month, 2 years, and 5 years postoperatively in both groups when compared with preoperative scores. Significant improvements in these scores were found in the MIS group at 1 month postoperatively, while at 2 years and 5 years postoperatively, both groups revealed comparable aforementioned scores. Excellent and perfect scale rating, interbody fusion rate, and adjacent segment degeneration prevalence between the groups were almost similar. CONCLUSIONS: Microendoscopy-assisted MIS-TLIF is comparable with open TLIF in terms of 5-year outcomes with additional benefits of reduced intraoperative iatrogenic injury, decreased initial pain, minimized activity restrictions, and accelerated ambulation recovery after surgery.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Microcirurgia/tendências , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Neuroendoscopia/tendências , Fusão Vertebral/tendências , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neuroendoscopia/métodos , Estudos Retrospectivos , Fusão Vertebral/métodos , Fatores de Tempo , Resultado do Tratamento
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(2): 192-197, 2018 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-29502059

RESUMO

OBJECTIVE: To assess the value of preoperative serum albumin level in predicting the survival of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing transurethral resection of bladder tumor (TURBT). METHODS: Two hundred and sixteen newly diagnosed patients with NMIBC who underwent TURBT between January, 2007 and April, 2012 were retrospectively analyzed. The patients were categorized into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups. The patient survival was estimated using the Kaplan-Meier method, and univariate and multivariate Cox proportional analyses were used to determine the hazard ratios (HRs) for the overall survival (OS). RESULTS: Of the patients with available data, 82 (39%) and 127 (61%) patients were classified into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups, respectively. Kaplan-Meier analysis showed a significantly worse 5-year OS in low albumin group than in normal albumin group (P=0.017). In the multivariate Cox regression analysis, after adjusting for confounding variables, the preoperative albumin level remained as an independent predictor for 5-year OS (HR: 3.102, 95%CI: 1.200-8.020, P=0.020). CONCLUSION: A low preoperative albumin level predicts a poor 5-year OS in patients with NMIBC who underwent TURBT. Preoperative serum albumin can be a good prognostic factor for predicting survival of the patients with NMIBC treated with TURBT.


Assuntos
Albumina Sérica Humana/análise , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/cirurgia , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
18.
Oncotarget ; 9(2): 1992-2001, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29416747

RESUMO

CD34 is a transmembrane phosphoglycoprotein used to selectively enrich bone marrow in hematopoietic stem cells for transplantation. Treating rats with CD34+ cells derived from human umbilical cord blood before or after heat stroke has been shown to promote survival. We investigated whether CD34- human placenta-derived stem cells (PDMSCs) could improve survival following heat stroke in rats. Rats were subjected to heat stress (42°C for 98 min) to induce heat stroke. Intravenous administration of PDMSCs 1 day before or immediately after the onset of heat stroke improved survival by 60% and 20%, respectively. Pre-treatment with CD34- PDMSCs protected against heat stroke injury more effectively than that treatment after injury. PDMSCs treatment attenuated cerebrovascular dysfunction, the inflammatory response, and lipid peroxidation. These data suggest human PDMSCs protect against heat stroke injury in rats. Moreover, these effects do not require the presence of CD34+ cells.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA