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1.
Geohealth ; 8(4): e2024GH001040, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651003

RESUMO

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long-term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B-Se) and urine selenium (U-Se) levels were detected in these areas, measuring 416.977 µg/L and 352.690 µg/L and 104.527 µg/L and 51.820 µg/L, respectively. Additionally, the median blood Cd (B-Cd) and urine Cd (U-Cd) levels were markedly elevated at 4.821 µg/L and 3.848 µg/L and at 7.750 µg/L and 7.050 µg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 µmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 µmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent.

2.
Molecules ; 29(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38542876

RESUMO

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.


Assuntos
Lesão Pulmonar Aguda , Cebolinha-Francesa , Medicamentos de Ervas Chinesas , Saponinas , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Saponinas/farmacologia , Lipopolissacarídeos/toxicidade , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Células Endoteliais da Veia Umbilical Humana , Fator de Necrose Tumoral alfa/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Mediadores da Inflamação/metabolismo
3.
JAMA Netw Open ; 7(3): e240953, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38446480

RESUMO

Importance: Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant. Objective: To investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD. Design, Setting, and Participants: A single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis. Interventions: Patients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients. Main Outcomes and Measures: The primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42. Results: A total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], -1.17 [0.44]; 95% CI, -2.04 to -0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03). Conclusions and Relevance: These results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100054199.


Assuntos
Depressão Pós-Parto , Ketamina , Adulto , Feminino , Humanos , Gravidez , Adjuvantes Imunológicos , Cesárea , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/prevenção & controle , Ketamina/uso terapêutico , Adolescente , Adulto Jovem
4.
Cyborg Bionic Syst ; 5: 0063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188983

RESUMO

Respiratory motion-induced vertebral movements can adversely impact intraoperative spine surgery, resulting in inaccurate positional information of the target region and unexpected damage during the operation. In this paper, we propose a novel deep learning architecture for respiratory motion prediction, which can adapt to different patients. The proposed method utilizes an LSTM-AE with attention mechanism network that can be trained using few-shot datasets during operation. To ensure real-time performance, a dimension reduction method based on the respiration-induced physical movement of spine vertebral bodies is introduced. The experiment collected data from prone-positioned patients under general anaesthesia to validate the prediction accuracy and time efficiency of the LSTM-AE-based motion prediction method. The experimental results demonstrate that the presented method (RMSE: 4.39%) outperforms other methods in terms of accuracy within a learning time of 2 min. The maximum predictive errors under the latency of 333 ms with respect to the x, y, and z axes of the optical camera system were 0.13, 0.07, and 0.10 mm, respectively, within a motion range of 2 mm.

5.
J Clin Invest ; 134(6)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38271117

RESUMO

BACKGROUNDThe tumor immune microenvironment can provide prognostic and therapeutic information. We aimed to develop noninvasive imaging biomarkers from computed tomography (CT) for comprehensive evaluation of immune context and investigate their associations with prognosis and immunotherapy response in gastric cancer (GC).METHODSThis study involved 2,600 patients with GC from 9 independent cohorts. We developed and validated 2 CT imaging biomarkers (lymphoid radiomics score [LRS] and myeloid radiomics score [MRS]) for evaluating the IHC-derived lymphoid and myeloid immune context respectively, and integrated them into a combined imaging biomarker [LRS/MRS: low(-) or high(+)] with 4 radiomics immune subtypes: 1 (-/-), 2 (+/-), 3 (-/+), and 4 (+/+). We further evaluated the imaging biomarkers' predictive values on prognosis and immunotherapy response.RESULTSThe developed imaging biomarkers (LRS and MRS) had a high accuracy in predicting lymphoid (AUC range: 0.765-0.773) and myeloid (AUC range: 0.736-0.750) immune context. Further, similar to the IHC-derived immune context, 2 imaging biomarkers (HR range: 0.240-0.761 for LRS; 1.301-4.012 for MRS) and the combined biomarker were independent predictors for disease-free and overall survival in the training and all validation cohorts (all P < 0.05). Additionally, patients with high LRS or low MRS may benefit more from immunotherapy (P < 0.001). Further, a highly heterogeneous outcome on objective response ​rate was observed in 4 imaging subtypes: 1 (-/-) with 27.3%, 2 (+/-) with 53.3%, 3 (-/+) with 10.2%, and 4 (+/+) with 30.0% (P < 0.0001).CONCLUSIONThe noninvasive imaging biomarkers could accurately evaluate the immune context and provide information regarding prognosis and immunotherapy for GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/terapia , Radiômica , Imunoterapia , Tomografia Computadorizada por Raios X , Microambiente Tumoral , Biomarcadores , Prognóstico
6.
Front Immunol ; 14: 1303491, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077355

RESUMO

Immune checkpoint inhibitors (ICIs) therapy has emerged as a promising treatment strategy for breast cancer (BC). However, current reliance on immunohistochemical (IHC) detection of PD-L1 expression alone has limited predictive capability, resulting in suboptimal efficacy of ICIs for some BC patients. Hence, developing novel predictive biomarkers is indispensable to enhance patient selection for immunotherapy. In this context, utilizing liquid biopsy (LB) can provide supplementary or alternative value to PD-L1 IHC testing for identifying patients most likely to benefit from immunotherapy and exhibit favorable responses. This review discusses the predictive and prognostic value of LB in breast cancer immunotherapy, as well as its limitations and future directions. We aim to promote the individualization and precision of immunotherapy in BC by elucidating the role of LB in clinical practice.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Biópsia Líquida , Imunoterapia/métodos
7.
Molecules ; 28(22)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38005247

RESUMO

The Nod-like receptor family PYRIN domain containing 3 (NLRP3) inflammasome is a multiprotein signaling complex that plays a pivotal role in innate immunity, and the dysregulated NLRP3 inflammasome activation is implicated in various diseases. Tiliroside is a natural flavonoid in multiple medicinal and dietary plants with known anti-inflammatory activities. However, its role in regulating NLRP3 inflammasome activation and NLRP3-related disease has not been evaluated. Herein, it was demonstrated that tiliroside is inhibitory in activating the NLRP3 inflammasome in macrophages. Mechanistically, tiliroside promotes AMP-activated protein kinase (AMPK) activation, thereby leading to ameliorated mitochondrial damage as evidenced by the reduction of mitochondrial reactive oxygen species (ROS) production and the improvement of mitochondrial membrane potential, which is accompanied by attenuated NLRP3 inflammasome activation in macrophages. Notably, tiliroside potently attenuated lipopolysaccharide (LPS)-induced acute lung injury in mice, which has been known to be NLRP3 inflammasome dependent. For the first time, this study identified that tiliroside is an NLRP3 inflammasome inhibitor and may represent a potential therapeutic agent for managing NLRP3-mediated inflammatory disease.


Assuntos
Lesão Pulmonar Aguda , Inflamassomos , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Macrófagos/metabolismo , Flavonoides/metabolismo , Lesão Pulmonar Aguda/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos/farmacologia
8.
NPJ Precis Oncol ; 7(1): 117, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932419

RESUMO

The response rate of cancer immune checkpoint inhibitors (ICI) varies among patients, making it challenging to pre-determine whether a particular patient will respond to immunotherapy. While gene mutation is critical to the treatment outcome, a framework capable of explicitly incorporating biology knowledge has yet to be established. Here we aim to propose and validate a mutation-based deep learning model for survival analysis on 1571 patients treated with ICI. Our model achieves an average concordance index of 0.59 ± 0.13 across nine types of cancer, compared to the gold standard Cox-PH model (0.52 ± 0.10). The "black box" nature of deep learning is a major concern in healthcare field. This model's interpretability, which results from incorporating the gene pathways and protein interaction (i.e., biology-aware) rather than relying on a 'black box' approach, helps patient stratification and provides insight into novel gene biomarkers, advancing our understanding of ICI treatment.

9.
J Virol Methods ; 322: 114806, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37689373

RESUMO

Viral diseases have become a significant impediment to the sustainable development of the global shrimp aquaculture industry. Decapod iridescent virus 1 (DIV1) is an emerging shrimp virus that has affected shrimp in China recent years. Rapid detection of DIV1 could improve enhance the effectiveness of prevention, control and treatment in the absence of good prevention and control measures. This study established loop-mediated isothermal amplification (LAMP) along with two visual interpretation methods, LAMP-dye and LAMP-LFD, to detect DIV1. The newly developed method would not cause cross-reactions with other shrimp pathogens such as white spot syndrome virus (WSSV), infectious hypodermal and hematopoietic necrosis virus (IHHNV), Enterocytozoon hepatopenaei (EHP), and Vibrio parahaemolyticus acute hepatopancreatic necrosis disease (VpAHPND). The detection limit of DIV1 LAMP was as low as 103 copies of DIV1 per reaction, with a reaction time of less than 40 min. The diagnostic sensitivity and diagnostic specificity of this method were determined to be 88% and 100%, respectively, when compared with the conventional PCR. Both of the LAMP-dye and LAMP-LFD methods are cost-effective and do not require expensive amplification equipment. They can be combined with LAMP and other temperature amplification methods for rapid on-site detection, effectively prevent aerosol contamination, and which are convenient and suitable for field testing or preliminary infection rish prediction experiments to predict the risk of infection.


Assuntos
Penaeidae , Animais , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase/métodos , Primers do DNA , China , Sensibilidade e Especificidade
10.
Food Funct ; 14(4): 2223-2238, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36757840

RESUMO

Probiotic Enterococcus hirae WEHI01 and Enterococcus faecium WEFA23 from infants were previously found to effectively inhibit the development of melanoma. In this study, their immunomodulatory and antitumor mechanisms were systemically studied. In vitro assay showed that E. hirae WEHI01 and E. faecium WEFA23 achieved biphasic immune regulation, which was revealed by the activation of resting spleen lymphocytes and RAW264.7 macrophages, as well as the anti-inflammation effect when immune cells were treated with LPS. The antitumor effects of E. hirae WEHI01 and E. faecium WEFA23 in vitro and vivo were then investigated. CCK8 and the cell scratch assay showed that the conditioned media, which were co-incubated with Enterococcus and spleen lymphocytes, significantly inhibited the proliferation and migration of B16F10, HepG-2 and HT-29 cells. The results of the tumor-bearing mice model experiment showed that E. faecium WEFA23 inhibition of the growth of tumors in mice, and the anti-tumor mechanism involved three aspects, namely tumor proliferation (decreasing expressions of LDHA, VEGF, MMP2, MMP9 and HIF-1α), inhibition of the pro-inflammation state (decreasing expressions of IL-6, TGF-ß and IL-17) and the promotion of apoptosis (increasing expression of Bax/Bcl-2, caspase-3 and p53). The results suggest that the two strains of Enterococcus could be promising candidates for treating melanoma with a highly inhibitory effect.


Assuntos
Enterococcus faecium , Melanoma , Camundongos , Animais , Enterococcus , Enterococcus faecium/fisiologia , Apoptose , Proliferação de Células
11.
Foods ; 11(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35954073

RESUMO

Aquatic products have an important role in global agriculture, but the challenges associated with preservation have limited their marketability. Essential oil (EO), such as sweet orange oil (SOEO), has been widely used for preservation due to its excellent antibacterial ability. However, the volatilization of EO limits its application in food preservation. In this study, SOEO was extracted from sweet orange peel by steam distillation and then stored in microcapsules. The components of the microcapsules were as follows: the porous starch was chosen as an adsorbed substrate to store SOEO (PS/SOEO), and sodium alginate (SA) and chitosan (CMCS) were used as shell material to delay the volatilization of SOEO using the sharp pore coagulation method. Our results showed that the main antibacterial ingredients in SOEO were aldehydes (33.93%) and d-limonene (15.38%). The microcapsules were of an irregular shape (oval), and the size of the microcapsules was 1.2 ± 0.1 cm as measured by a digital micrometer. Scanning electron microscopy (SEM) results showed that there were a lot of pores on the surface of the starch after modification, but sodium alginate and chitosan could well encapsulate these pores. The results of Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis also showed that SOEO was successful encapsulated into the porous starch. The results of compression test and releasing kinetics studies suggested that CMCS and SA improved the mechanical and slow-releasing ability of SOEO microcapsules. The best antibacterial performance was obtained when 0.8 g of SOEO microcapsules was added. Finally, the shelf life of crawfish could be extended to 6 days by SOEO microcapsule (1/10 g, SOEO microcapsule/crawfish) under room temperature. These results provide a systematic understanding of the antibacterial capabilities of sweet orange essential oil microcapsules, which can contribute to the development of preservation methods for aquatic products.

12.
Crit Rev Food Sci Nutr ; 62(19): 5307-5321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33635174

RESUMO

Inflammatory bowel disease (IBD) is a chronic gastro-intestinal disorders of unknown etiology. There are several drugs approved for treating IBD patients with active disease, including first-line use of aminosalicylates, and secondary choices of immunomodulators and other therapies. These medications might manage disease symptoms, but have also shown significant side-effects in IBD patients. Tea is the second largest beverage in the world and its main active ingredients including tea polyphenols, polysaccharides and tea pigments have been shown promising anti-inflammatory and antioxidant properties. In this review, we summarize the influence of different tea varieties including green tea, black tea and dark tea as potential nutritional therapy for preventing and treating IBD, and discuss the mechanisms of tea ingredients involved in the regulation of oxidative stress, inflammation, signaling pathways, and gut microbiota that could benefit for IBD disease management. Our observation directs further basic and clinical investigations on tea polyphenols and their derivatives as novel IBD therapeutic agents.


Assuntos
Doenças Inflamatórias Intestinais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Chá/metabolismo
13.
Front Genet ; 11: 554502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193628

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive form of pancreatic cancer. Its 5-year survival rate is only 3-5%. Perineural invasion (PNI) is a process of cancer cells invading the surrounding nerves and perineural spaces. It is considered to be associated with the poor prognosis of PDAC. About 90% of pancreatic cancer patients have PNI. The high incidence of PNI in pancreatic cancer limits radical resection and promotes local recurrence, which negatively affects life quality and survival time of the patients with pancreatic cancer. OBJECTIVES: To investigate the mechanism of PNI in pancreatic cancer, we analyzed the gene expression profiles of tumors and adjacent tissues from 50 PDAC patients which included 28 patients with perineural invasion and 22 patients without perineural invasion. METHOD: Using Monte-Carlo feature selection and Incremental Feature Selection (IFS) method, we identified 26 key features within which 15 features were from tumor tissues and 11 features were from adjacent tissues. RESULTS: Our results suggested that not only the tumor tissue, but also the adjacent tissue, was informative for perineural invasion prediction. The SVM classifier based on these 26 key features can predict perineural invasion accurately, with a high accuracy of 0.94 evaluated with leave-one-out cross validation (LOOCV). CONCLUSION: The in-depth biological analysis of key feature genes, such as TNFRSF14, XPO1, and ATF3, shed light on the understanding of perineural invasion in pancreatic ductal adenocarcinoma.

14.
J Mater Chem B ; 8(44): 10126-10135, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33074279

RESUMO

Excess aggregation of amyloid ß peptide (Aß) is a fatal cause of Alzheimer's disease (AD), which leads to physiological toxicity. Inhibiting and disaggregating the Aß aggregates is an effective strategy to reduce physiological toxicity in neuronal cells. Herein, conjugated polymer-based thermoresponsive micelles (CPMs) were designed with an efficient thermoresponsive surface and a reactive-oxygen-species (ROS)-generating core. In this work, the CPMs exhibited a strong capability to capture the toxic Aß aggregates at physiological temperature. Under white-light irradiation, ROS was generated in the CPMs, and the toxic Aß aggregates were efficiently disaggregated through the oxidation of ROS, leading to appropriate Aß homeostasis between aggregation and disaggregation and reduced the Aß-induced cytotoxicity. Therefore, the multifunctional micelles of CPMs with both capturing shells and ROS functional cores present a promising strategy to reduce Aß fibrillation-induced cytotoxicity.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Temperatura Alta , Micelas , Fragmentos de Peptídeos/antagonistas & inibidores , Polietilenoglicóis/síntese química , Polímeros/síntese química , Agregados Proteicos/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células PC12 , Fragmentos de Peptídeos/metabolismo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Polímeros/administração & dosagem , Polímeros/metabolismo , Agregados Proteicos/fisiologia , Ratos
15.
Biochem Pharmacol ; 178: 114062, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32492446

RESUMO

To overcome the adverse effects of conventional chemotherapy for cancers, various nanoparticles based drug delivery systems have been developed. However, nanoparticles delivering drugs directly to kill tumor cells still faced with challenges, because tumors possessed adopt complex mechanism to resist damages, which compromised the therapeutic efficacy. TMEM16A/CaCCs (Calcium activates chloride channels) has been identified to be overexpressed in lung adenocarcinoma which can serve as a novel tumor specific drug target in our previous work. Here, we developed a novel dual-targeted antitumor strategy via designing a novel nano-assembled, pH-sensitive drug-delivery system loading with specific inhibitors of TMEM16A against lung adenocarcinoma. For validation, we assayed the novel dual-targeting therapy on xenograft mouse model which exhibited significant antitumor activity and not affect mouse body weight. The dual targeting therapy accomplished in this study will shed light on the development of advanced antitumor strategy.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Anoctamina-1/antagonistas & inibidores , Anoctamina-1/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pulmonares/metabolismo , Nanopartículas/administração & dosagem , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Nus
16.
Appl Microbiol Biotechnol ; 104(12): 5493-5504, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32314005

RESUMO

The bacterium-bacterium interaction between pathogenic and probiotic Enterococcus as well as the bacterium-host interaction between Enterococcus and intestinal epithelium has drawn increasing attentions, but the influence of those interactions on host pregnancy remains largely unexplored. In the present study, we evaluated the effects of probiotic E. faecalis Symbioflor 1 or/and pathogenic E. faecalis OG1RF on the miscarriage of pregnant mice. Using in vitro assays of competition and exclusion and displacement, antagonistic property of E. faecalis Symbioflor 1 against E. faecalis OG1RF was observed, and the former inhibited the translocation of the later in vivo. The rate of miscarriage induced by E. faecalis OG1RF challenge was significantly reduced by 28% with E. faecalis Symbioflor 1 intervention; and the tissue integrity of ileum, colon, uterus, and placenta and placental blood cell density in pregnant mice were drastically improved by such probiotic intervention. Compared with the controls, probiotic intervention significantly upregulated the level of IL-10 and TGF-ß, downregulated levels of IFN-γ, and increased progesterone level that reversed the trend of being Th1 predominance state reported for adverse pregnancy outcome at early pregnancy stage. In conclusion, E. faecalis Symbioflor 1 decreased the translocation of E. faecalis OG1RF, prevented pathogen-induced tissue damage, and changed Th1-Th2 homeostasis toward Th2 predominance during early pregnancy resulting in decreased miscarriage. KEY POINTS: •The mechanism of how probiotic E. faecalis Symbioflor 1 improves pregnancy of mice • Influence of interactions of pathogenic and probiotic Enterococcus on host pregnancy • E. faecalis Symbioflor 1 change Th1-Th2 homeostasis toward Th2 predominance.


Assuntos
Aborto Espontâneo/microbiologia , Aborto Espontâneo/prevenção & controle , Antibiose , Enterococcus faecalis/fisiologia , Probióticos/administração & dosagem , Células Th1/imunologia , Células Th2/imunologia , Animais , Translocação Bacteriana , Citocinas/imunologia , Enterococcus faecalis/patogenicidade , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Gravidez , Progesterona/sangue , Organismos Livres de Patógenos Específicos
17.
Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165747, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32109492

RESUMO

OBJECTIVE: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. The study aimed to investigate the effects and molecular mechanism of miR-139-5p/SLC7A11 on the proliferation and metastasis of PANC. METHODS: Bioinformatics was used to analyze the differentially expressed genes in the TCGA database. PANC cell lines with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and have been used to detect cell proliferation, invasion and metastasis of PANC Subsequently, bioinformatic analysis and dual luciferase reporter assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mice model was used to explore the functions of miR-139-5p in PANC tumorigenicity. RESULTS: MiR-139-5p could regulate and affect the protein expression of P13K and Akt associated with phosphatidylinositol signaling pathway by inhibiting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, invasion and metastasis could be inhibited by miR-139-5p overexpression and be promoted by SLC7A11 overexpression. MiR-139-5p overexpression could suppress PANC tumor growth and the expressions of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibitory of miR-139-5p to PANC cell proliferation, invasion and metastasis was partly due to its inhibiting effect on SLC7A11 expression. CONCLUSION: Our study proves that miR-139-5p/SLC7A11 has important functions on PANC, suggesting that miR-139-5p can be used as a biomarker for PANC patients.


Assuntos
Sistema y+ de Transporte de Aminoácidos/genética , Carcinogênese/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Proteína Oncogênica v-akt/genética , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/genética , Neoplasias Pancreáticas
18.
J Laparoendosc Adv Surg Tech A ; 29(12): 1571-1576, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31682205

RESUMO

Objectives: To investigate the effect of autologous blood transfusion (ABT) and Pringle maneuver (PM) on postoperative early liver function and short-term postoperative results following laparoscopic liver resection in patients with benign hepatic neoplasms. Materials and Methods: We retrospectively analyzed the clinical data for 125 consecutive patients who underwent laparoscopic segmental hepatectomy from January 2015 to May 2018 (68 in the ABT group versus 57 in the PM group). We compared patients' characteristics and intra- and postoperative short-term outcomes between the groups. Results: The 2 groups were well matched regarding patients' clinical characteristics, types of liver resection, operative time, and histopathological findings (P > .05). Median blood loss was significantly lower in the PM group versus the ABT group (200 mL versus 750 mL, respectively; P < .01), and overall complication rates were similar (n = 12 [17%] versus n = 9 [16%], respectively; P > .05). The ABT group had significantly lower mean levels of total bilirubin, indirect bilirubin, aspartate transaminase, and alanine aminotransferase on postoperative days 1 and 3 (P < .05). The ABT group had a shorter hospital stay compared with the PM group (5.8 days versus 7.7 days, respectively; P < .05) and lower hospitalization costs (55,400 ± 15,400 versus 667,000 ± 21,600 CN dollars, respectively; P < .05). Conclusions: Compared with Pringle's maneuver, laparoscopic hepatectomy with ABT promoted early recovery of liver function and reduced hospitalization costs in select patients with benign hepatic neoplasms.


Assuntos
Transfusão de Sangue Autóloga , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos
19.
Viruses ; 11(4)2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027252

RESUMO

In this study, ridgetail white prawns-Exopalaemon carinicauda-were infected per os (PO) with debris of Penaeus vannamei infected with shrimp hemocyte iridescent virus (SHIV 20141215), a strain of decapod iridescent virus 1 (DIV1), and via intramuscular injection (IM with raw extracts of SHIV 20141215. The infected E. carinicauda showed obvious clinical symptoms, including weakness, empty gut and stomach, pale hepatopancreas, and partial death with mean cumulative mortalities of 42.5% and 70.8% by nonlinear regression, respectively. Results of TaqMan probe-based real-time quantitative PCR showed that the moribund and surviving individuals with clinical signs of infected E. carinicauda were DIV1-positive. Histological examination showed that there were darkly eosinophilic and cytoplasmic inclusions, of which some were surrounded with or contained tiny basophilic staining, and pyknosis in hemocytes in hepatopancreatic sinus, hematopoietic cells, cuticular epithelium, etc. On the slides of in situ DIG-labeling-loop-mediated DNA amplification (ISDL), positive signals were observed in hematopoietic tissue, stomach, cuticular epithelium, and hepatopancreatic sinus of infected prawns from both PO and IM groups. Transmission electron microscopy (TEM) of ultrathin sections showed that icosahedral DIV1 particles existed in hepatopancreatic sinus and gills of the infected E. carinicauda from the PO group. The viral particles were also observed in hepatopancreatic sinus, gills, pereiopods, muscles, and uropods of the infected E. carinicauda from the IM group. The assembled virions, which mostly distributed along the edge of the cytoplasmic virogenic stromata near cellular membrane of infected cells, were enveloped and approximately 150 nm in diameter. The results of molecular tests, histopathological examination, ISDL, and TEM confirmed that E. carinicauda is a susceptible host of DIV1. This study also indicated that E. carinicauda showed some degree of tolerance to the infection with DIV1 per os challenge mimicking natural pathway.


Assuntos
Decápodes/virologia , Suscetibilidade a Doenças/veterinária , Hemócitos/virologia , Iridovirus/genética , Viroses/veterinária , Animais , Clonagem Molecular , Suscetibilidade a Doenças/virologia , Injeções Intramusculares , Iridovirus/patogenicidade , Filogenia , Viroses/mortalidade , Viroses/fisiopatologia
20.
Viruses ; 11(4)2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999644

RESUMO

Macrobrachium rosenbergii is a valuable freshwater prawn in Asian aquaculture. In recent years, a new symptom that was generally called "white head" has caused high mortality in M. rosenbergii farms in China. Samples of M. rosenbergii, M. nipponense, Procambarus clarkii, M. superbum, Penaeus vannamei, and Cladocera from a farm suffering from white head in Jiangsu Province were collected and analyzed in this study. Pathogen detection showed that all samples were positive for Decapod iridescent virus 1 (DIV1). Histopathological examination revealed dark eosinophilic inclusions and pyknosis in hematopoietic tissue, hepatopancreas, and gills of M. rosenbergii and M. nipponense. Blue signals of in situ digoxigenin-labeled loop-mediated isothermal amplification appeared in hematopoietic tissue, hemocytes, hepatopancreatic sinus, and antennal gland. Transmission electron microscopy of ultrathin sections showed a large number of DIV1 particles with a mean diameter about 157.9 nm. The virogenic stromata and budding virions were observed in hematopoietic cells. Quantitative detection with TaqMan probe based real-time PCR of different tissues in naturally infected M. rosenbergii showed that hematopoietic tissue contained the highest DIV1 load with a relative abundance of 25.4 ± 16.9%. Hepatopancreas and muscle contained the lowest DIV1 loads with relative abundances of 2.44 ± 1.24% and 2.44 ± 2.16%, respectively. The above results verified that DIV1 is the pathogen causing white head in M. rosenbergii. M. nipponense and Pr. clarkii are also species susceptible to DIV1.


Assuntos
Infecções por Vírus de DNA/veterinária , Iridoviridae/fisiologia , Palaemonidae/virologia , Frutos do Mar/virologia , Animais , Aquicultura , China , Infecções por Vírus de DNA/virologia , Suscetibilidade a Doenças , Água Doce/virologia , Iridoviridae/genética , Iridoviridae/isolamento & purificação , Iridoviridae/ultraestrutura , Carga Viral
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